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Chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. The CSDH outer membrane, which contains inflammatory cells, plays an important role in CSDH development. Osteopontin (OPN) is an extracellular matrix protein that is cleaved by thrombin, generating the N-terminal half of OPN, which is prominently involved in integrin signal transduction. We explored the expression of the N-terminal half of OPN in CSDH fluid and the expression of integrins α9 and β1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. Twenty samples of CSDH fluid and 8 samples of CSDH outer membrane were included. The concentrations of the N-terminal half of OPN in CSDH fluid samples were measured using ELISA kits. The expression levels of integrins α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin were examined by western blot analysis. The expression levels of integrins α9 and β1, FAK and paxillin were also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. The concentration of the N-terminal half of OPN in CSDH fluid was significantly higher than that in the serum. Western blot analysis confirmed the presence of these molecules. In addition, integrins α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. Our data suggest that the N-terminal half of OPN in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-terminal half of OPN, which is part of the extracellular matrix, plays a critical role in the promotion of CSDH.

Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Chemokines attract leukocytes, and invading neutrophils and monocytes/macrophages play important roles in wound healing. However, no studies have been reported regarding changes in expression of chemokines in CSDH fluid after trepanation surgery. We randomly divided patients who underwent trepanation surgery into two groups. One was the irrigation group, in which irrigation of CSDH fluids was performed and a drainage tube was placed (

We present a case series of underwater microvascular decompression (MVD) for hemifacial spasm (HFS) and an evaluation of its feasibility and safety. This retrospective study was conducted at a single institution and included 20 patients with HFS who underwent underwater MVD between September 2019 and January 2021. Surgery was performed in 3 steps, as follows: exoscopic wound opening (soft tissue, bone, dura, and arachnoid around the cerebellomedullary cistern), underwater endoscopic surgery (decompression of the facial nerve), and exoscopic wound closure. In underwater endoscopic surgery, the surgical field was continuously irrigated with artificial cerebrospinal fluid. Abnormal muscle response and brainstem auditory evoked potentials (BAEPs) were monitored. Neurovascular conflicts were clearly observed in all patients without fogging and soiling of the endoscope lens. HFS was completely relieved in 19 patients (95%). An amplitude reduction of wave V of BAEPs of more than 50% was not observed in any of the cases. In 5 cases (25%), the latency of wave V of BAEPs was prolonged for more than 1.0 ms; these changes completely or near completely returned to baseline values at dural closure in all 5 cases. A postoperative complication of transient facial palsy was observed in 1 patient (5%) during postoperative days 10–30. There were no other complications. Our findings suggest that underwater MVD is a safe and feasible option for the treatment of HFS. However, it did not show advantages over conventional endoscopic MVD when the protective effect on the eighth cranial nerve was evaluated.

Chronic subdural hematoma (CSDH) is an angiogenic disease that is involved with many inflammatory mediators. Tie2 is predominantly expressed in the embryonic endothelium and plays an important role in the maturation and stabilization of the vasculature. Angiopoietin (Ang)1 and Ang2 are well-known ligands of the Tie2 receptor. We examined the expression of Ang1 and Ang2 in CSDH fluid and the expression of Tie-2 receptor and components of the angiogenic signaling pathways in the outer membrane of CSDH. Twenty-five samples of CSDH fluid and eight samples of outer membrane of CSDH were included. The concentrations of Ang1 and Ang2 in the CSDH fluid were measured using enzyme-linked immunosorbent assay (ELISA) kits. The expression of Tie2, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) mechanistic target of rapamycin (mTOR), GβL, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E (eIF-4E), and β-actin was examined by a Western blot analysis. The expression of Tie2, Akt, and mTOR was also examined by immunohistochemistry. The concentration of Ang2 in CSDH fluid was significantly higher than that in the serum or cerebrospinal fluid (CSF), and also higher than that of Ang1 in CSDH fluid. Tie2, PI3K, Akt, mTOR, GβL, p70S6K, and eIF-4E were detected in all cases. In addition, Tie2, Akt, and mTOR were localized in the endothelial cells of vessels in the CSDH outer membrane. Our data suggest that Ang2, although not Ang1, in CSDH fluid promotes angiogenesis in endothelial cells through the Tie2 receptor. The Ang2/Tie2 signaling pathway might therefore be a useful therapeutic target for treating the growth of intractable CSDH.

Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2-weeks of cast immobilization in chronic post-cast pain (CPCP) rat model. In the present study, we also demonstrated dystrophy-like changes, both peripheral nociceptive signals and activation of the central pain pathway in CPCP rats. This was done by the following methods: (1) vascular permeability (Evans blue dye) and inflammatory- and oxidative stress-related messenger RNA (mRNA) changes (real-time quantitative polymerase chain reaction); (2) immunofluorescence of pERK and/or c-Fos expression in the spino-parabrachio-amygdaloid pathway; and (3) blockade of nociceptive-related signals using sciatic nerve block (SNB). Furthermore, we demonstrated tactile allodynia using an optogenetic method in a transgenic rat line (W-TChR2V4), cold allodynia using the acetone test, and activation of dorsal horn neurons in the chronic phase associated with chronic mechanical hyperalgesia using c-Fos immunofluorescence. In addition, we showed that nociceptive signals in the acute phase are involved in chronic pathological pain-like behaviors by studying the effects of SNB. Thus, we conclude that physical disuse contributes to dystrophy-like changes, spontaneous pain-like behavior, and chronic widespread pathological pain-like behaviors in CPCP rats after 2 weeks of cast immobilization.

Chronic subdural hematoma (CSDH) is considered to be an inflammatory and angiogenic disease. Osteopontin is an extracellular matrix protein. Osteopontin is cleaved by thrombin, resulting in N-half osteopontin, which is more prominent in integrin signal transduction. We examined the expression of N-half osteopontin in the CSDH fluid and the expression of integrin α9 and β1 and the downstream components of the angiogenic signaling pathways in the outer membrane of CSDHs. Twenty samples of CSDH fluid and 8 samples of CSDH outer membrane were included. The concentrations of N-half osteopontin in the CSDH fluid were measured using ELISA kits. The expression of integrin α9 and β1, vinculin, talin-1, focal adhesion kinase (FAK), paxillin, α-actin, Src and β-actin was examined by western blot analysis. The expression of integrin α9 and β1, FAK and paxillin was also examined by immunohistochemistry. We investigated whether CSDH fluid could activate FAK in cultured endothelial cells in vitro. The concentration of N-half osteopontin in CSDH fluid was significantly higher than that in the serum. Western blot analysis revealed above-mentioned molecules. In addition, integrin α9 and β1, FAK and paxillin were localized in the endothelial cells of vessels within the CSDH outer membrane. FAK was significantly phosphorylated immediately after treatment with CSDH fluid. Our data suggest that N-half osteopontin in CSDH fluid promotes neovascularization in endothelial cells through integrins α9 and β1. The N-half osteopontin and integrin signaling pathway might be a useful therapeutic target for treating the growth of refractory CSDH.

Objective Craniofacial resection (CFR) and temporal bone resection (TBR) on malignant head and neck tumors (MHNTs) invading skull base require accurate and precise determination of the tumor invasion. We investigated tumor skull base invasion patterns and surgical results in CFR and TBR cases. Methods We performed either CFR or TBR for 75 selected patients with the possibility of en bloc resection over the period between 2011 and 2018. The medical charts of the selected patients were reviewed. Results Primary tumor onset site (TOS) groups were: (1) nasal cavity/ethmoid sinus, 20 cases; (2) orbit, 10 cases; (3) maxillary sinus, 28 cases; and (4) external ear/temporomandibular joint, 17 cases. Grades for tumor invasion depth (TID) included: (I) extracranial invasion and skull base bone invasion; (II) extradural invasion; or (III) intradural invasion. Patients in groups 1 and 2 had a significantly higher frequency of grade II and III invasions than patients in groups 3 and 4. The main invasion site was nasal cavity superior wall and ethmoid sinus superior wall for group 1 tumors, orbit superior wall, and lateral skull base sphenoid bone for group 2 and 3 tumors, and lateral skull base temporal bone for group 4 tumors. Positive resection margins represented a significant negative prognostic factor. TID and TOS did not affect skull base margin status. Conclusion Skull base invasion of MHNTs exhibits certain fixed patterns in sites susceptible to invasion based on the TOS. The frequencies of extradural and intradural invasions differed, indicating the importance for accurate preoperative tumor evaluation.

Previous studies showed that complement activation is associated with poor functional outcome after aneurysmal subarachnoid hemorrhage (SAH). We investigated whether complement activation is underlying brain injury after aneurysmal SAH (n = 7) and if it is an appropriate treatment target. We investigated complement expression in brain tissue of aneurysmal SAH patients (n = 930) and studied the role of common genetic variants in C3 and C5 genes in outcome. We analyzed plasma levels (n = 229) to identify the functionality of a single nucleotide polymorphism (SNP) associated with outcome. The time course of C5a levels was measured in plasma (n = 31) and CSF (n = 10). In an SAH mouse model, we studied the extent of microglia activation and cell death in wild-type mice, mice lacking the C5a receptor, and in mice treated with C5-specific antibodies (n = 15 per group). Brain sections from aneurysmal SAH patients showed increased presence of complement components C1q and C3/C3b/iC3B compared to controls. The complement component 5 (C5) SNP correlated with C5a plasma levels and poor disease outcome. Serial measurements in CSF revealed that C5a was > 1400-fold increased 1 day after aneurysmal SAH and then gradually decreased. C5a in plasma was 2-fold increased at days 3–10 after aneurysmal SAH. In the SAH mouse model, we observed a ≈ 40% reduction in both microglia activation and cell death in mice lacking the C5a receptor, and in mice treated with C5-specific antibodies. These data show that C5 contributes to brain injury after experimental SAH, and support further study of C5-specific antibodies as novel treatment option to reduce brain injury and improve prognosis after aneurysmal SAH.

Objective The purpose of this study was to determine the sensitivity and specificity of using the spinal midline (M line) on a radiographic anteroposterior (AP) view for detecting pedicle screws (PSs) breaching the medial pedicle wall. Methods We retrospectively reviewed 145 patients who underwent fusion surgery using PSs between January 2006 and May 2017. We defined the M line as a line that connected the upper and lower spinous processes through the fixed vertebrae. The M line was positive if the tip of the PS crossed the M line. The reference standard was a computed tomography scan. The reliability of the M line was examined. Results The subjects included 145 patients (70 men and 75 women; mean age, 63.4 years). A total of 599 PSs were examined. Most cases were because of spondylolisthesis (66.9%). Most screws were inserted at a lower lumber level (77.6%). Analysis of the diagnostic accuracy of the M line yielded a sensitivity of 74.1% and a specificity of 95.3%. In addition, the positive predictive value of the M line was 42.6%, and the negative predictive value of the M line was 98.7%. Conclusions Assessment of the M line via an intraoperative radiographic AP view is a simple, readily available, complementary method for detecting PSs that have breached the medial pedicle wall in the thoracic, lumbar, and sacral spine. In particular, the M line has a strong negative predictive value, which is much more meaningful.

Objective Neutrophils induce inflammation through the exocytosis of cytotoxic granule proteins. Recently, neutrophils have been reported to be an independent parameter associated with unfavorable outcomes after subarachnoid hemorrhage (SAH). However, the mechanism by which neutrophils accumulate within the CSF after SAH remains undetermined. Methods Concentrations of C5a, epithelial neutrophil activating peptide 78 (ENA-78), interleukin-8 (IL-8), growth-regulated oncogene-α (GRO-α), neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO) were measured serially until day 14 in the CSF of 10 patients with SAH. CSF samples obtained from patients suffering from unruptured aneurysms were used as controls. Results The concentrations of C5a and ENA-78 were significantly increased on day 1, while those of IL-8 and GRO-α significantly increased during days 3–7 compared with those of the control samples. The levels of NGAL and MPO, components of neutrophil granules, significantly increased during days 1–5 and days 1–3, respectively, after SAH and gradually decreased thereafter. The correlations between ENA-78 and C5a on day 1, IL-8 and GRO-α on days 3–7, and NGAL and MPO on days 1–3 were significant. Conclusion These neutrophil chemoattractants might be serially involved in the infiltration of neutrophils into the CSF after SAH. Migrated neutrophils play an important role in inflammatory reactions in the central nervous system after SAH.

Objective To review the authors' surgical experience with radical temporal bone resection (TBR) with an emphasis on the classification of skull base osteotomy and transcranial tympanotomy (TCT) that is required for middle ear transection. Methods We reviewed the records of 25 patients who underwent radical TBR at our facilities between 2011 and 2020. Results The osteotomy line of radical TBR was divided into 3 segments: anterior (A), medial (M), and posterior (P). Each segment was further classified as follows: A1, through the glenoid fossa (1 patient); A2, in front of the glenoid fossa (23 patients); A3, through the greater wing of the sphenoid bone (1 patient); M1, through the middle ear (16 patients); M2, through the inner ear (9 patients); P1, through the mastoid (9 patients); and P2, through the posterior cranial fossa (16 patients). The M segment was significantly associated with operation time and intraoperative blood loss. In all patients with M1 osteotomy, TCT was performed; TCT was classified into superior and far posterior approaches. A superior approach was performed in all 16 patients, whereas the far posterior approach was performed in only 7 patients with both M1 and P2 osteotomy. Conclusions Our newly proposed osteotomy classification of radical TBR is suitable for minute but clinically important adjustment of the osteotomy line. TCT is an indispensable technique for M1 osteotomy; our newly proposed classification expands our understanding of TCT and how to incorporate this technique into radical TBR.

Chronic subdural hematoma (CSDH) is fundamentally treatable, although it sometimes recurs. We observed, however, several cases of spontaneous resolution of CSDH outer membranes, even in a trabecular type of CSDH, after a trepanation surgical procedure. In this study, we examined the expression of molecules of the autophagy signaling pathway in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation were included in this study. By Western blot analysis, we examined the expression of mammalian target of rapamycin (mTOR); GβL; UNC-51-like kinase-1 (ULK1); Beclin-1; autophagy-related genes (Atg) 3, 5, 7, 12, 13, and 16L1β,α; the autophagy marker Light Chain3A/B (LC3A/B); and β-actin, which constitute the autophagy signaling pathway. The expression levels of Beclin-1, Atg12, and LC3A/B were also examined by immunohistochemistry. Almost all of these molecules could be detected in all samples. Beclin-1, Atg12, and LC3A/B were found to be localized in the endothelial cells of vessels and fibroblasts in CSDH. We detected molecules of the autophagy signaling pathway in CSDH outer membranes. Autophagy contributes to the tissue homeostatic process, maintaining cellular integrity by clearing debris. Our data suggest that autophagy might play an important role in the spontaneous resolution of CSDH. Therefore, these molecules may be novel therapeutic targets for the treatment of those with CSDH.

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Introduction We previously demonstrated that cyclic AMP-dependent protein kinase (PKA) phosphorylates neuronal nitric oxide synthase (nNOS) at Ser1412 in the hippocampal dentate gyrus after forebrain ischemia; this phosphorylation event activates NOS activity and might contribute to depression after cerebral ischemia. In this study, we revealed chronological and topographical changes in the phosphorylation of nNOS at Ser1412 immediately after subarachnoid hemorrhage (SAH). Methods In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24 h after SAH. Samples from rats that were not injected with autologous blood were used as controls. NOS was partially purified from crude samples via an ADP-agarose gel. Levels of nNOS, nNOS phosphorylated at Ser1412 (p-nNOS), PKA, and p-PKA at Thr197 were studied in the rat hippocampus and cortex using Western blot analyses and immunohistochemistry. Results According to the Western blot analysis, levels of p-nNOS at Ser1412 were significantly increased in the hippocampus, but not in the cortex, between 1 and 3 h after SAH. Immunohistochemistry revealed the phosphorylation of nNOS at Ser1412 and PKA at Thr197 in the dentate gyrus, but not in the CA1 area, 1 h after SAH. An injection of saline instead of blood also significantly increased levels of p-nNOS at Ser1412 in the hippocampus 1 h after the injection. Conclusions An immediate increase in intracranial pressure (ICP) might induce transient cerebral ischemia and promote the PKA-mediated phosphorylation of nNOS at Ser1412 in the dentate gyrus. This signal transduction pathway induces the excessive production of nitric oxide (NO) and might be involved in cognitive dysfunction after SAH.

Eosinophils induce inflammation by releasing cytokines and cytotoxic granule proteins. Infiltration of eosinophilic granulocytes occurs in the outer membrane of chronic subdural hematomas (CSDHs). Eosinophils play an important role in the growth of CSDHs. However, the manner in which eosinophils accumulate within CSDH fluid remains undetermined. In the current study, we assessed the expression of eosinophil chemoattractants in CSDH fluids according to growth stage of CSDHs and examined the correlation between the two. CSDH fluids were obtained from 38 patients during trepanation surgery. Ecalectin, eotaxin-3, interleukin-5 (IL-5), and eosinophil-derived neurotoxin (EDN) concentrations were measured using enzyme-linked immunosorbent assay kits. For use as controls, serum samples were collected from 5 healthy adults, and cerebrospinal fluid (CSF) samples were collected from 5 adults with unruptured aneurysms. The percentage of eosinophils (%eosinophil) in CSDH fluids was calculated using Giemsa staining. Concentrations of ecalectin, eotaxin-3, IL-5, and EDN were nearly equivalent in serum and CSF samples; however, their concentrations were high in CSDH fluids. In particular, ecalectin and EDN levels in CSDH fluids were significantly higher than those in serum and CSF. Levels of eotaxin-3, IL-5, EDN, and %eosinophil were significantly higher in laminar type of CSDH, whereas that of ecalectin was not. The correlations between eotaxin-3 and IL-5, IL-5 and EDN, and EDN and %eosinophil were statistically significant (p 0.01). Our data suggest that eotaxin-3 is a chemoattractant of eosinophils. IL-5 induces the activation of eosinophils subsequent to degranulation of EDN into CSDH fluids. These factors may serve as novel therapeutic targets for managing CSDH.

We previously demonstrated that the inflammatory cytokine interleukin-6 (IL-6) activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway in fibroblasts within the outer membranes of chronic subdural hematomas (CSDHs), and the activation of this pathway may induce CSDH outer membrane growth. The inhibitory system for this signal transduction pathway is unknown. CSDH fluids were obtained from 10 patients during trepanation surgery as the case group, and cerebrospinal fluid (CSF) samples were obtained from seven patients suffering from subarachnoid hemorrhage (SAH) on Day 1 as the control group. The concentrations of IL-6, soluble IL-6 receptor (sIL-6R), and soluble gp130 (sgp130) in CSDH fluid and CSF were measured using enzyme immunoassay kits. The co-localization of IL-6 and sgp130 in CSDH fluid was examined by immunoprecipitation. The expression levels of STAT3, JAK2, suppressor of cytokine signaling 3 (SOCS3), and protein inhibitor of activated Stat3 (PIAS3) in the outer membranes of CSDHs were examined by immunostaining. Soluble IL-6R and sgp130 concentrations in CSDH fluid were significantly higher than those in CSF after SAH. Sgp130 and IL-6 were co-immunoprecipitated from CSDH fluid. Immunostaining revealed STAT3, JAK2, SOCS3, and PIAS3 expression in fibroblasts located in the outer membranes of CSDHs. Soluble gp130 binds to IL-6/sIL-6R and acts as an antagonist of the JAK/STAT signaling pathway. SOCS3 also binds to JAK and inhibits its signaling pathway. In addition, PIAS3 regulates STAT3 activation. These factors might down-regulate the IL-6/JAK/STAT signaling pathway in fibroblasts within CSDH outer membranes. Therefore, these molecules may be novel therapeutic targets for the inhibition of CSDH growth.

Background Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF. Methods The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated ( p )-STAT3, and actin was examined by Western blot analysis. The expression of p -STAT3 was also examined by immunostaining and its positive cell ratio was compared between LSS and non-LSS samples. We measured the thickness of the LF on magnetic resonance images and studied the relationship between its thickness and the expression of p -STAT3. Results JAK1, STAT3, and p -STAT3 were detected in almost all samples by Western blot analysis. Immunoreactivity against p -STAT3 was observed mainly in endothelial- and fibroblast-like cells. The expression of p -STAT3 was significantly higher in LSS than non-LSS samples; it was significantly stronger on the dorsal than the dural side of the LF and positively correlated with the thickness of the LF on the dorsal side. Conclusions The JAK/STAT signaling pathway is positively correlated with the thickness of the LF. Our findings suggest that JAK1 and STAT3 molecules are involved in and regulate LF hypertrophy.

Objective This study investigated the diagnostic accuracy of the difference in the cross-sectional areas (CSAs) of affected cervical nerve roots (NRs) for diagnosing cervical radiculopathy (CR). Methods In total, 102 CR patients and 219 healthy volunteers were examined with ultrasound. The CSA of the cervical NR at each level was measured on the affected side and the contralateral side in CR patients by blinded ultrasonographic technicians. The difference between the CSAs of CR patients and normal volunteers and the difference in the laterality of CSA at the same affected level (ΔCSA) were calculated for each cervical level. Results The CSAs of the affected NRs in CR patients were significantly larger than those of the unaffected NRs in CR patients and those of the control group at the C5, C6 and C7 levels (P

Objective The resection of foramen magnum meningiomas (FMMs) presents neurosurgical challenges. We propose a simple classification of the tumor location and the operating space created by the tumor to help treatment planning. Methods We retrospectively analyzed 16 FMMs and divided them into 3 groups based on the tumor location—clival, foraminal, and atlantal tumors. The distance between the condyle and the neuraxis at the level of the foramen magnum was measured and defined as the available operative space (AOS). We also reviewed intraoperative video recordings to assess the surgical exposure of the tumor by the space created by the FMM and compared it with the AOS. Results There were 4 clival, 8 foraminal, and 4 atlantal tumors. The AOS of the clival tumors was 10 mm ± 1.7, the AOS of the foraminal tumors was 18 mm ± 3.7, and the AOS of the atlantal tumors was 12 mm ± 2.1. All foraminal and atlantal tumors could be detached without a brain retractor. Because a major portion of the clival tumors was covered by the spinomedullary junction, a brain spatula was needed to obtain the required surgical space. The difference in AOS between clival and foraminal/atlantal tumors was statistically significant (P = 0.044). Although 4 patients experienced postoperative complications, the average postoperative Karnofsky performance scale score improved. The surgical complication rate was significantly lower in foraminal and atlantal FMMs than in clival FMMs (P = 0.027). Conclusions The simple classification of the tumor location helped to assess surgical difficulties. Knowledge of the space created by the FMMs between the condyle and the neuraxis is useful for planning the approach strategy, especially for estimating the available working space without resection of the occipital condyle.

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is highly abundant in the brain and exhibits broad substrate specificity, thereby it is thought to participate in the regulation of neuronal death and survival. Nitric oxide (NO), produced by neuronal NO synthase (nNOS), is an important neurotransmitter and plays a role in neuronal activity including learning and memory processes. However, high levels of NO can contribute to excitotoxicity following a stroke and neurodegenerative disease. Aside from NO, nNOS also generates superoxide which is involved in both cell injury and signaling. CaMKII is known to activate and translocate from the cytoplasm to the post-synaptic density in response to neuronal activation where nNOS is predominantly located. Phosphorylation of nNOS at Ser847 by CaMKII decreases NO generation and increases superoxide generation. Conversely, NO-induced S-nitrosylation of CaMKII at Cys6 is a prominent determinant of the CaMKII inhibition in ATP competitive fashion. Thus, the “cross-talk” between CaMKII and NO/superoxide may represent important signal transduction pathways in brain. In this review, we introduce the molecular mechanism of and pathophysiological role of mutual regulation between CaMKII and nNOS in neurons.

Chronic subdural hematoma (CSDH) is an angiogenic and inflammatory disease. Toll-like receptors (TLRs) transduce intracellular signals, resulting in the activation of nuclear factor κB (NF-κB), which leads to the production of inflammatory cytokines. High-mobility group box 1 (HMGB1) functions as a mediator of inflammatory responses through TLRs. In this study, we examined the expression of HMGB1 and components of the Toll-like receptor and NF-κB signaling pathways in the outer membrane of CSDH. Eight patients whose outer membrane was successfully obtained during trepanation surgery were included in this study. The expression of TLR4, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 4 (IRAK4), TNF receptor-associated factor 6 (TRAF6), TGFβ-activated kinase 1 (Tak1), interferon regulatory factors 3 (IRF3), IκB kinase β (IKKβ), IKKγ, IκBε, IκBα, NF-κB/p65 and β-actin was examined by Western blot analysis. The expression of TLR4, NF-κB/p65 and interleukin-6 (IL-6) was also examined by immunohistochemistry. The concentrations of HMGB1 and IL-6 in CSDH fluids were measured using ELISA kits. Above-mentioned molecules were detected in all cases. In addition, TLR4, NF-κB/p65 and IL-6 were localized in the endothelial cells of vessels within CSDH outer membranes. The concentrations of HMGB1 and IL-6 in CSDH fluids were significantly higher than that in the CSF and serum. There existed a correlation between the concentrations of HMGB1 and IL-6 in CSDH fluids. Our data suggest that HMGB1 in CSDH fluids produces the inflammatory cytokine IL-6 in endothelial cells through the Toll-like receptor and NF-κB signaling pathways. Anti-HMGB1 therapy might be a useful method to treat the growth of CSDH.

Early brain injury has recently been identified as an indicator of poor prognosis after subarachnoid hemorrhage (SAH). Calmodulin-dependent protein kinase IIα (CaMKIIα) has been shown to phosphorylate neuronal NOS (nNOS) at Ser 847 , resulting in a reduction in nNOS activity. In this study, we revealed chronological changes in the phosphorylation of nNOS at Ser 847 in the hippocampus and cortex immediately after SAH. In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24 h after SAH. Samples from rats that were not injected with blood were used as controls. NOS was partially purified from the crude samples using ADP-agarose affinity chromatography. Western blot analysis revealed that nNOS phosphorylated (p-nNOS) at Ser 847 was significantly increased in the hippocampus, but not in the cortex, at 1 h after SAH compared with that resulting from the control treatment. Immunoreactivity of p-nNOS at Ser 847 was observed in interneurons of the hippocampus at 1 h after SAH. Injection of saline instead of blood also significantly induced p-nNOS at Ser 847 levels in the hippocampus at 1 h after injection. The colocalization of CaMKIIα and nNOS was transiently increased in the hippocampus at 0.5 h after SAH. Our data suggest that immediately after SAH, an increase in intracranial pressure might induce transient cerebral ischemia, potentially promoting the phosphorylation of nNOS at Ser 847 by CaMKIIα in the hippocampus. The activation of p-nNOS at Ser 847 in the hippocampus may alleviate ischemic insults immediately after SAH to exert a neuroprotective effect against early brain injury.

Growth factors and inflammatory cytokines activate the mitogen-activated protein kinase (MAPK) cascade. Previous studies have shown that chronic subdural hematoma (CSDH) fluid contains these factors and cytokines. In this study, expression of three major MAPK cascade transmitters in the outer membrane of CSDH was assessed. Eleven patients whose outer membrane and CSDH fluid were successfully obtained during trepanation surgery were included in this study. Expression of extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, p38, p-p38, c-Jun N-terminal kinase (JNK), p-JNK, and actin was examined by Western blot and immunostaining. We examined whether CSDH fluid could activate MAPKs in cultured endothelial cells (ECs) or fibroblasts in vitro. Western blot analysis showed that p-ERK was present in all samples, whereas p-p38 and p-JNK were detected, but not in all cases. Immunostaining showed that all three p-MAPKs were expressed in vascular endothelium. However, only p-ERK was expressed in fibroblasts. Expression of p-extracellular signal-regulated kinase kinase (MEK) and p-ERK in ECs and fibroblasts was significantly induced immediately after treatment with CSDH fluid, whereas p-p38 and p-JNK expression was significantly induced in ECs 60 min after treatment, but not in fibroblasts. Activation of MEK was significantly inhibited by treatment with antibodies directed against interleukin-6 and vascular endothelial growth factor in ECs, but not in fibroblasts. Inflammatory cytokines and growth factors in CSDH fluids might activate major MAPKs in ECs, which might be associated with neovascularization in the outer membrane of CSDH. These MAPK pathways could become novel targets for treatment of CSDHs.

Background Recently, various examination and intervention techniques using cervical nerve ultrasonography have been developed. The specific shapes of the C7 transverse process and vertebral artery in front of the C7 transverse process have become landmarks. Purpose To determine the prevalence of anomalies and anomalous vertebral artery entrances at the C7 transverse process. Material and Methods The records of patients who underwent plain or contrast-enhanced neck or cervical spine computed tomography (CT) were reviewed. The examinations were scored for the anomalous presence of anterior tubercles or cervical ribs as well as vertebral artery entrances in the C7 transverse process. The prevalence of anomalies was compared based on patient sex and age. Results Evaluating the examinations from 2067 patients (1046 men; 1021 women), 1% of patients exhibited an anomalous presence of anterior tubercles, and 0.3% of patients displayed cervical ribs at the C7 transverse process. The prevalence of anomalies process was significantly higher in men aged less than 40 years than in older men ( P Conclusion Although an anomalous vertebral artery entry into the C7 transverse foramen was rare, the prevalence of an anomaly at the C7 transverse process was higher in men aged less than 40 years. Therefore, we recommend performing CT in younger men before cervical nerve ultrasonographic intervention to avoid misinterpretations at the cervical level.

The medial branch of the posterior ramus of the lumbar spinal nerve is well known to be innervated independently and to end in the multifidus muscle without anastomosis. This prospective cohort study aimed to determine the diagnostic specificity and sensitivity of multifidus muscle denervation (MMD) by needle electromyography (N-EMG) for lumbar foraminal and lateral exit-zone stenosis (LF/LEZS). We enrolled 61 consecutive patients experiencing unilateral dysesthesia and/or leg pain in the L4 or L5 regions with suspicious LF/LEZS. The Japanese Orthopedic Association (JOA) score, Visual Analog Scale (VAS) for leg pain, and N-EMG were examined. In this study protocol, all patients received at least 3 months of conservative therapy. Surgery was performed on patients who experienced less than 50 % VAS pain relief compared with their initial score after confirming the responsible level by lumbar nerve root block. The specificity of N-EMG was the proportion of patients who improved with conservative therapies (non-surgery) after 3 months. The sensitivity of N-EMG was the proportion of patients who improved with surgical therapies (surgery) after more than 12 months. Twenty-three patients underwent surgery. The initial lower JOA, positive Kemp test and motor weakness were significantly higher in the surgery group. The MMD by N-EMG indicated that 34 of 38 patients were negative in the non-surgery group. In the surgery group, 21 of 23 patients were positive. The diagnostic sensitivity and specificity were 91.3 and 92.1 %, respectively. Needle electromyography is a simple and available additional method for the diagnosis of LF/LEZS.

Chronic subdural hematoma (CSDH) is fundamentally treatable through surgery, although CSDH recurs in some cases. We have observed several cases of spontaneous resolution of CSDH outer membranes, including in trabecular CSDH, after trepanation surgery. In this study, we examined the expression of molecules involved in caspase signaling in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation surgery were included in this study. The expression of Fas; Fas-associated death domain (FADD); tumor necrosis factor receptor type 1-associated death domain (TRADD); receptor-interacting protein (RIP); caspases 3, 7, 8, and 9; poly-(ADP-ribose) polymerase (PARP); DNA fragmentation factor 45 (DFF45) and β-actin was examined by Western blot analysis. The expression levels of PARP, caspase-3, and cleaved caspase-3 were also examined by immunohistochemistry. Fas; FADD; TRADD; RIP; caspases 3, 7, 8, and 9; PARP, and DFF45 were detected in nearly all samples. Caspase-3 and PARP were localized in the endothelial cells of vessels and in fibroblasts in CSDH outer membranes. In addition, cleaved caspase-3 was detected in fibroblasts. We detected molecules of the caspase signaling pathway in CSDH outer membranes. In particular, cleaved caspase-3 was detected, which suggests that apoptosis may occur within these membranes. Thus, during the growth of CSDH outer membranes, the caspase signaling pathway may be restrained. Once the pathway is activated, gradual resolution of CSDH outer membranes may occur. Therefore, these molecules may be novel therapeutic targets for intractable CSDH.

We previously demonstrated that cyclic AMP-dependent protein kinase (PKA) phosphorylates neuronal nitric oxide synthase (nNOS) at SerIn a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24 h after SAH. Samples from rats that were not injected with autologous blood were used as controls. NOS was partially purified from crude samples via an ADP-agarose gel. Levels of nNOS, nNOS phosphorylated at SerAccording to the Western blot analysis, levels of p-nNOS at SerAn immediate increase in intracranial pressure (ICP) might induce transient cerebral ischemia and promote the PKA-mediated phosphorylation of nNOS at Ser

The aim of this study was to examine the solid bone fusion rates between Plasmapore-coated titanium cages (PPC group) and non-Plasmapore-coated titanium cages (N-PPC group) in patients who received anterior cervical decompression and fusion (ACDF).Of 78 patients who received ACDF at the hospital, a follow-up period greater than 2 years was possible for 61 patients, including 30 in the PPC group and 42 in the N-PPC group. Evaluations were performed at 3, 6, 12, and 24 months after surgery. Radiological stabilization (RS) was defined as the restriction of spinous process movement to3 mm and the absence of a halo around the cages on flexion-extension radiographs. Solid bone fusion (SBF) was defined as the formation of bony bridges between the fixed vertebral bodies in sagittal computed tomography sections. The rates of RS and SBF were compared between both groups.The differences in RS were not significant between the 2 groups during the follow-up period. However, the SBF rates at 6 and 12 months were significantly higher in the PPC group (26.7% and 56.7%) than in the N-PPC group (5% and 21.4%). Moreover, 63.3% (19 of 30) of patients in the PPC group demonstrated RS at 3 months, and of these patients, SBF was observed in 100% (19 patients) after 24 months, respectively. In comparison, the SBF rates in the N-PPC group were 86%.Plasmapore-coated titanium cages enabled more rapid solid bone fusion. We suggest that these types of cages might help to reduce postoperative radiograms.

We report a rare case of cervical radiculopathy associated with facet hypertrophy and disc herniation. The patient was a 38-year-old woman with sudden-onset left arm pain. As conservative therapy failed to alleviate her symptoms she was referred to us. On physical examination she manifested no neurological deficits except pain and dysesthesia in the left C7 territory. Computed tomography revealed hypertrophic ossified changes in the left T1 facet joint with encroachment on the spinal canal. Magnetic resonance imaging showed compression of the spinal cord at C6/7 by disc herniation at C6/7. Anterior cervical decompression and fusion by corpectomy (C7 corpectomy and C6/T1 fixation with a titanium cage) ameliorated her pain. Facet hypertrophy in a morphologically normal cervicothoracic spine is extremely rare and its etiology is unknown. We speculate the possibility that our patient harbored a congenital anomaly and that the morphologic changes were the consequence of an injury she sustained in a traffic accident.

In this paper the authors report the case of a patient with ossification of the posterior longitudinal ligament (OPLL) below the axial vertebra (C-2) at the kyphotic cervical spine, with an atlas vertebra (C-1) posterior arch that compressed the spinal cord with the head in a pathognomonic position, similar to a protruded position. This condition appears to be very rare. The morphological findings between the kyphotic cervical spine and OPLL, the upper occipitocervical junction, and the protruded-head position are discussed. A 40-year-old man presented with severe pain radiating to both legs when he yawned, sneezed, or extended his jaw (a protruded-head position). A kyphotic cervical spine with OPLL below C-2 was observed using CT and radiography, yet sagittal T2-weighted MRI failed to identify abnormal findings in a neutral or extension position, except for a slight cervical canal stenosis. However, in a pathognomonic protruded-head position, sagittal T2-weighted MRI showed a C-1 posterior arch that severely compressed the spinal cord at the upper cervical level. Therefore, the authors believe that the severe pain radiating to both legs was caused by a spinal canal stenosis due to a C-1 posterior arch impingement. The C-1 posterior arch was resected, and after the surgery, the patient indicated that the intolerable pain had disappeared. In conclusion, in patients with OPLL and a kyphotic cervical spine, the authors propose that the pathognomonic protruded position is valuable for estimating disrupted compensatory mechanisms at the upper cervical junction.

Chronic subdural hematoma (CSDH) is an inflammatory disease, the mechanism of which still remains to be elucidated. Interleukin-6 (IL-6), one of the inflammatory cytokines regulating janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway, is expressed in human CSDH fluid. The status of this signaling pathway in human CSDH outer membranes was examined in the present study using outer membranes obtained during trepanation surgery. Concentrations of IL-6 in human CSDH fluids were measured using an enzyme immuno-assay kit. Expression patterns of JAK1, STAT1, phosphorylated (p)-STAT1 at Tyr(701) and at Ser(727), STAT3, p-STAT3 at Tyr(705) and at Ser(727) and actin in outer membranes were examined by Western blot analysis and immunohistochemistry. IL-6 is significantly expressed in human CSDH fluids compared with control cerebrospinal fluid. JAK1, STAT1 and STAT3 were detected in all cases. The expression of p-STAT3 at Tyr(705) is more significant compared with that of p-STAT1 at Tyr(701). In some cases, p-STAT3 at Ser(727) could also be detected, while p-STAT1 at Ser(727) could not. The localizations of STAT1 and STAT3 were revealed to be present in fibroblasts in human CSDH outer membranes, especially when p-STAT3 at Tyr(705) was in the nuclei of fibroblasts. These findings suggest that JAK1-STAT3 signaling is dominantly activated in fibroblasts of human CSDH outer membranes compared with STAT1 and indicate the possibility that this JAK1-STAT3 pathway might be activated by IL-6 and play a critical role in progression of human CSDH.

Background Interleukin-6 (IL-6), an inflammatory cytokine, plays important roles in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Chemokines are chemoattractant cytokines that regulate trafficking of monocytes/macrophages and lymphocytes to sites of inflammation. However, no studies have been reported regarding the temporal expression of these cytokines in CSF after SAH. Findings The concentrations of IL-6, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-inducible protein-10 (IP-10), and monokine induced by interferon-γ (MIG) in the CSF of ten patients with SAH were measured using ELISA kits over a period of 14 days. All aneurysms were located in the anterior circulation. CSF samples from patients with unruptured aneurysms were used as controls. The concentration of IL-6 significantly increased during the acute stage of the disease. The concentration of MCP-1 increased from days 1 to 5, peaking on day 3, and decreased thereafter. The concentrations of IP-10 and MIG progressively increased, peaked on day 5, and then gradually decreased. There were strong correlations between the maximum levels of IL-6 and MCP-1 and IP-10 and MIG on day 5. The maximum level of IL-6 was much higher in poor outcome patients than in good outcome patients. Conclusions The present investigation demonstrated that increases in IL-6 levels may induce the expression of MCP-1 in CSF after SAH, followed by increases in the expression of IP-10 and MIG. Dynamic changes in the levels of these cytokines may induce inflammation and may be closely associated with the development of delayed ischemic neurological deficits after SAH. Electronic supplementary material The online version of this article (doi:10.1186/s12974-016-0675-7) contains supplementary material, which is available to authorized users.

Objective Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Interleukin-6, a well-known inflammatory cytokine, activates the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. We previously reported that the JAK/STAT pathway is activated in fibroblasts in the outer membrane of CSDH. More recently, signal transducer and activator of transcription 3 (STAT3) has been shown to have a role in angiogenesis. We examined the expression of STAT3 in endothelial cells in the outer membrane of CSDH. Methods This study included 7 patients whose outer membranes were successfully obtained during trephination surgery. The expression of STAT3 and phosphorylated STAT3 was examined by Western blot analysis and immunohistochemistry. We also examined whether CSDH fluid could activate STAT3 in cultured endothelial cells in vitro. Results STAT3 and phosphorylated STAT3 were detected in all cases. Immunostaining showed that STAT3 and phosphorylated STAT3 were expressed not only in fibroblasts but also in vascular endothelium. Expression of phosphorylated STAT3 in endothelial cells was significantly induced immediately after treatment of CSDH fluid in vitro. The activation of STAT3 was significantly inhibited by treatment with antibodies that were directed against interleukin-6; however, this was suppressed by antibodies that were directed against vascular endothelial growth factor, but not significantly. Conclusions Interleukin-6 might dominantly activate STAT3 in endothelial cells, which might have a central role in endothelial cell proliferation and angiogenesis of CSDH outer membranes.

Hypothermia has been shown to have neuroprotective effects against neurotrauma and cerebrovascular disease. Cerebral ischemia induces the activation of calcium/calmodulin kinase II (CaM-KII), which modulates many enzymes. We have previously demonstrated that CaM-KIIα downregulates neuronal nitric oxide synthase (nNOS) activity. However, precise details regarding the neuroprotective mechanism of hypothermia largely remain to be elucidated. Therefore, in this study, we investigated the neuroprotective mechanism of hypothermia, focusing on the association between CaM-KIIα and nNOS in CA1 hippocampus after focal cerebral ischemia in mice. The temperature was maintained at normothermia (36.5-37.5°C) or mild hypothermia (31.5-32.5°C) during these procedures. Focal cerebral ischemia induced significant dissociation of CaM-KIIα from nNOS in the CA1 hippocampus but not in the cerebral cortex under normothermia. Hypothermia did not change the expression of nNOS, but it significantly induced the colocalization of CaM-KIIα with nNOS in CA1 hippocampus immediately after cerebral ischemia. These results presumably result in the attenuation of nNOS activity and could contribute to the tolerance to post-ischemic damage. This effect could be one of the neuroprotective mechanisms of hypothermia.

Chronic subdural hematoma (CSDH) is an angiogenic disease that is recognized as a cause of treatable dementia with unknown pathogenesis. Vascular endothelial growth factor (VEGF), a potent growth factor regulating angiogenesis through the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway, has been implicated in its etiology. The status of this signaling pathway in CSDH outer membranes was examined in the present study, using outer membranes obtained during trepanation surgery. Expressions of PI3-kinase, PKB-kinase, Akt, phosphorylated Akt at Ser(473) (p-Akt), endothelial nitric oxide synthase (eNOS), vascular endothelial-cadherin (VE-cadherin), and actin were examined by Western blot analysis, together with their immunohistochemistry. PI3-kinase, Akt, eNOS, and VE-cadherin were detected in all cases. The magnitude of the expression of p-Akt varied among cases; however, the localization was revealed to be present in endothelial cells of vessels in CSDH outer membranes, together with VEGF and VE-cadherin detected in endothelial cells of vessels. These findings suggest that the PI3-kinase/Akt signaling is activated in CSDH outer membranes, and indicate the possibility that the PI3 kinase/Akt pathway might be activated by VEGF and play a critical role in the angiogenesis of CSDH.

Taurine has multiple functions in the central nervous system (CNS), serving as an osmoregulator, antioxidant, inhibitory neuromodulator, and regulator of intracellular Ca(2+) flux. Since the role of taurine in traumatic spinal cord injury (SCI) is not fully understood, the present study was conducted with C57 black/6 mice (18-20 g) who underwent severe SCI at the Th-8 level using a weight compression device. Taurine was injected intraperitoneally at doses of 25, 80, 250, and 800 mg/kg within 30 min after SCI. Controls were injected with saline. The contusional cord segments were removed 6 h after SCI, and concentrations of interleukin-6 (IL-6) and myeloperoxidase (MPO) were measured using ELISA kits. Phosphorylation of STAT3, which is activated by IL-6, and expression of inducible cyclooxygenase-2 (COX-2) were also compared between the taurine treatment group (250 mg/kg) and the control group by Western blot analysis. Morphological changes were evaluated with HE-stained sections. Taurine significantly decreased IL-6 and MPO levels in a dose-dependent manner, significantly reducing the phosphorylation of STAT3 and expression of COX-2 after SCI compared to controls. A reduced accumulation of neutrophils, especially in the subarachnoid spaces, and secondary degenerative changes in gray matter were also noted, and motor disturbances were significantly attenuated with taurine treatment (250 mg/kg). These findings indicate that taurine has anti-inflammatory effects against SCI, and may play a neuroprotective role against secondary damage, and thus it may have therapeutic potential.

Severe subarachnoid hemorrhage (SAH) induces dysfunction of endothelial nitric oxide synthase (eNOS), resulting in severe vasospasm. Clinically, however, some portions of cerebral arteries may show only mild vasospasm. Although severe vasospastic arteries after SAH have been intensively studied, activity of eNOS associated with the mild form of the disease has received less attention. The purpose of the present study was to clarify molecular mechanisms underlying the regulation of eNOS activity in mild vasospastic arteries after SAH. In a rat single-hemorrhage model, basilar arteries were obtained up to 7 days after SAH. Western blot analysis was used to study the temporal profiles of eNOS, phosphorylated (p)-eNOS at Ser(1177) or Thr(495), inducible NOS (iNOS), AMP-activated protein kinase alpha (AMPK alpha, p-AMPK alpha at Thr(172)Akt, p-Akt at Ser(473), cyclic AMP-dependent protein kinase (PKA), and p-PKA at Thr(197) in basilar arteries. Immunohistochemical studies were performed to examine the spatial expression patterns of p-eNOS at Ser(1177) and p-AMPK alpha at Thr(172). Western blot analysis showed eNOS to be significantly phosphorylated at Ser(1177) from 1 to 2 days after SAH, accompanied by upregulation of iNOS and AMPK, while activation states of Akt and PKA did not show significant change. Immunohistochemistry revealed phosphorylation of eNOS and AMPK alpha in endothelial cells of the basilar artery. SAH might thus induce temporary activation of AMPK alpha, which phosphorylates eNOS at Ser(1177) in endothelial cells of mild vasospastic basilar arteries. This signal transduction may play an important role in controlling cerebral blood flow after SAH.

Endothelial nitric oxide synthase (eNOS) plays a neuroprotective role after cerebral ischemia through the production of NO, which enhances cerebral blood flow. However, precise details regarding activation of eNOS after spinal cord injury (SCI) largely remain to be elucidated. In the present study we investigated chronological alteration and cellular location of eNOS and phosphorylated (p)-eNOS at Ser1177 following SCI in mice. Western blot analysis showed eNOS to be significantly phosphorylated at Ser1177 from 1 to 2 days after mild SCI, with gradual decrease thereafter. Immunohistochemistry revealed the p-eNOS to be mainly expressed in the endothelial cells of microvessels within gray matter under these conditions. These findings suggest that mild SCI activates eNOS in the subacute stage, which increases spinal cord blood flow and may be involved in protective and repair responses.

Background Chronic subdural hematoma (CSDH) is considered an angiogenic and inflammatory disease. Nuclear factor-kappa B (NF-κB) induces the production of inflammatory cytokines and adhesion molecules, which play an essential role in angiogenesis and inflammation. Recently, the double-stranded RNA-activated protein kinase (PKR) was shown to directly interact with NF-κB subunits to influence its transcriptional activity. Objective To examine the expression of NF-κB signaling pathway components and PKR in CSDH outer membranes. Methods Eight patients whose outer membranes were successfully obtained during trepanation surgery were included in this study. The IκBα, IKKβ, IKKγ, NF-κB, phosphorylated ( p )-NF-κB, and PKR expression levels were examined using western blotting analysis. NF-κB expression was also examined using immunohistochemistry. We investigated whether CSDH fluid could activate NF-κB in cultured endothelial cells in Vitro. Results The IκBα, IKKβ, IKKγ, and NF-κB levels were approximately the same. Additionally, p -NF-κB and PKR were detected at similar levels. Immunostaining showed that NF-κB was expressed in the vascular endothelium. p -NF-κB expression in endothelial cells was significantly induced immediately after treatment with CSDH fluid. Furthermore, NF-κB activation was significantly inhibited by treatment with antibodies directed against vascular endothelial growth factor. Conclusion PKR might activate NF-κB through vascular endothelial growth factor in endothelial cells, which might be associated with endothelial cell proliferation in the CSDH outer membrane. Thus, the NF-κB signaling pathway could play a critical role in CSDH growth.

BACKGROUND The impaction bone grafting technique is a popular approach for achieving complete bone fusion during hip surgery or total knee arthroplasty. We hypothesized that compaction bone grafting (CBG), a modified version of impaction bone grafting, could be applied to lumbar fusion surgery. OBJECTIVE To compare the bone fusion rates and durations achieved using the CBG technique and a conventional loose bone grafting technique. METHODS We retrospectively reviewed 89 patients who underwent single-level posterior lumbar interbody fusion at the university hospital; 35 other posterior lumbar interbody fusion recipients were excluded due to undergoing multilevel fusion, prior lumbar surgery, trauma, infection, or inadequate computed tomographic data. Computed tomographic-based bone fusion assessments were obtained using the Brantigan, Steffee, and Fraser criteria at 1 and 2 years after surgery. RESULTS The baseline characteristics of the CBG (n = 42) and loose bone grafting (n = 47) groups did not significantly differ. Fusion assessments indicated that significantly superior bone fusion rates were achieved at 1 year after surgery in the CBG group than in the loose bone grafting group (P = .04, χ2 test). However, the bone fusion rates of the 2 groups at 2 years after surgery did not significantly differ (P = .3). A nonsymptomatic surgical complication occurred in the CBG group when a spacer was inserted into the intervertebral space; specifically, the spacer slipped out of the right psoas muscle because a large quantity of compaction bone grafts disrupted the cage's pathway. CONCLUSION In posterior lumbar interbody fusion surgeries, bone fusion was achieved more quickly with the CBG technique than with the conventional technique.

Early brain injury has recently been identified as an indicator of poor prognosis after subarachnoid hemorrhage (SAH). Calmodulin-dependent protein kinase IIα (CaMKIIα) has been shown to phosphorylate neuronal NOS (nNOS) at Ser(847), resulting in a reduction in nNOS activity. In this study, we revealed chronological changes in the phosphorylation of nNOS at Ser(847) in the hippocampus and cortex immediately after SAH. In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24h after SAH. Samples from rats that were not injected with blood were used as controls. NOS was partially purified from the crude samples using ADP-agarose affinity chromatography. Western blot analysis revealed that nNOS phosphorylated (p-nNOS) at Ser(847) was significantly increased in the hippocampus, but not in the cortex, at 1h after SAH compared with that resulting from the control treatment. Immunoreactivity of p-nNOS at Ser(847) was observed in interneurons of the hippocampus at 1h after SAH. Injection of saline instead of blood also significantly induced p-nNOS at Ser(847) levels in the hippocampus at 1h after injection. The colocalization of CaMKIIα and nNOS was transiently increased in the hippocampus at 0.5h after SAH. Our data suggest that immediately after SAH, an increase in intracranial pressure might induce transient cerebral ischemia, potentially promoting the phosphorylation of nNOS at Ser(847) by CaMKIIα in the hippocampus. The activation of p-nNOS at Ser(847) in the hippocampus may alleviate ischemic insults immediately after SAH to exert a neuroprotective effect against early brain injury.

BACKGROUND CONTEXT: Previous conventional magnetic resonance imaging reports on extraforaminal entrapment (e-FE) on L5–S1 have been problematic because of their complexity or lack of sensitivity and specificity. In this study, we propose a simple diagnostic method for e-FE. PURPOSE: The purpose of this study was to determine the sensitivity and specificity of using the difference in the foraminal spinal nerve (FSN) angle of the L5 nerve, as determined by oblique coronal T2-weighted imaging (OC-T2WI), for diagnosing L5–S1 unilateral e-FE. STUDY DESIGN: The study design involves diagnostic accuracy with retrospective case-control study. PATIENT SAMPLE: Seventy consecutive patients with unilateral L5 radiculopathy who underwent unilateral L5–S1 extraspinal canal decompression for e-FE or 4/5 intraspinal canal decompression for lumbar spinal canal stenosis between 2009 and 2013 were included. OUTCOME MEASURES: The Japanese Orthopedic Association score, Visual Analog Scale score for leg pain, and OC-T2WI for the FSN angle of the L5 nerve were examined. METHODS: The 70 patients were divided into two groups: Group A (n521) with unilateral L5– S1 e-FE and Group B (n549) with intraspinal canal L4–L5. Group C (n544) comprised the control group, which included only patients with back pain without leg radiculopathy. All patients underwent OC-T2WI, and the differences in the FSN angle of the fifth lumbar spinal nerve between the symptomatic and asymptomatic sides (DFSN angle) were examined and compared among the groups. RESULTS: There were no significant differences in the patient characteristics among the three groups. The DFSN angle was 17 � in Group A, 4.8 � in Group B, and 6.4 � in Group C, and the laterality was significantly larger in Group A than in the other two groups. A receiver-operating characteristic curve showed areas under the curve between groups A and B and between groups A and C of 0.93 and 0.97, respectively. In addition, the cutoff value of the DFSN angle (10 � ) indicated diagnostic accuracies of 94% and 91% (sensitivity and specificity) and of 93% and 95%, respectively. CONCLUSIONS: Determining differences in the FSN angle between the symptomatic and asymptomatic sides of greater than 10 � via OC-T2WI represented a simple, readily