Search

Chronic subdural hematoma (CSDH) in posterior fossa is rare, and its pathogenesis and treatment remain unclear. In this study, we report a case of a patient with CSDH in the posterior fossa who was taking warfarin and underwent middle meningeal artery (MMA) embolization successfully. A 59-year-old man taking warfarin for a mechanical aortic valve presented with a complaint of hearing impairment. He then developed headaches and was referred to our hospital after the previous physician identified CSDH above and below the left tentorium cerebelli on computed tomography (CT). We conducted MMA embolization with n-butyl-2-cyanoacrylate while continuing anticoagulation therapy. Right after the day of the surgery, symptoms of hearing impairment and right hemiplegia immediately improved. He was discharged after 10 days of hospitalization and was able to walk independently. His symptoms disappeared 20 days after surgery. There was no recurrence 100 days after surgery. In this study, we experienced a case of a CSDH in the posterior fossa that was clinically improved by MMA embolization. MMA embolization is a useful option for nonspecific CSDH without interruption of warfarin therapy., Competing Interests: The authors declare no conflict of interest regarding the materials or methods used in this study or the findings specified in this paper. The research was approved by the institutional ethics committee. The consent was obtained from all the participants., (© 2024 The Japan Neurosurgical Society.)

Affinity maturation increases antigen-binding affinity and specificity of antibodies by somatic hypermutation. Various monoclonal antibodies against (4-hydroxy-3-nitrophenyl)acetyl (NP) were obtained during affinity maturation. Among them, highly matured anti-NP antibodies, such as E11 and E3, possess Cys96 H and Cys100 H in the complementarity-determining region 3 of the heavy chain, which would form a disulfide bond. In this study, we evaluated the effects of disulfide bonds on antigen binding by generating single-chain Fv (scFv) antibodies of E11 and its mutants, E11_C96K H /C100E H and E11_C96K H /C100Q H , and determined their antigen-binding thermodynamics and kinetics. The binding affinities of the Cys mutants were lower than that of E11 scFv, indicating that the disulfide bond contributed to antigen binding, especially for stable complex formation. This was also supported by the decreased affinity of E11 scFv in the presence of a reducing agent. The crystal structures of NP-free and NP-bound E11 scFvs were determined at high resolution, showing the existence of a disulfide bond between Cys96 H and Cys100 H , and the antigen recognition mechanism, which could be compared with those of other anti-NP antibodies, such as germline-type N1G9 and matured-type C6, as reported previously. These structures could explain the molecular basis of changes in antigen-binding affinity and thermal stability in the absence or presence of antigens. Small-angle X-ray scattering further showed a local conformational change in E11 scFv upon antigen binding in solution., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure., (© 2024. The Author(s).)

We have applied our advanced computational and experimental methodologies to investigate the complex structure and binding mechanism of a modified Wilms' Tumor 1 (mWT1) protein epitope to the understudied Asian-dominant allele HLA-A*24:02 (HLA-A24) in aqueous solution. We have applied our developed multicanonical molecular dynamics (McMD)-based dynamic docking method to analyze the binding pathway and mechanism, which we verified by comparing the highest probability structures from simulation with our experimentally solved x-ray crystal structure. Subsequent path sampling MD simulations elucidated the atomic details of the binding process and indicated that first an encounter complex is formed between the N-terminal's positive charge of the 9-residue mWT1 fragment peptide and a cluster of negative residues on the surface of HLA-A24, with the major histocompatibility complex (MHC) molecule preferring a predominantly closed conformation. The peptide first binds to this closed MHC conformation, forming an encounter complex, after which the binding site opens due to increased entropy of the binding site, allowing the peptide to bind to form the native complex structure. Further sequence and structure analyses also suggest that although the peptide loading complex would help with stabilizing the MHC molecule, the binding depends in a large part on the intrinsic affinity between the MHC molecule and the antigen peptide. Finally, our computational tools and analyses can be of great benefit to study the binding mechanism of different MHC types to their antigens, where it could also be useful in the development of higher affinity variant peptides and for personalized medicine., (© 2023 The Protein Society.)

Background: Vagus nerve stimulation (VNS) exerts neuroprotective and anti-inflammatory effects in preclinical models of central nervous system disorders, including Parkinson's disease (PD). VNS setting applied for experimental models is limited into single-time or intermittent short-duration stimulation. We developed a VNS device which could deliver continuous stimulation for rats. To date, the effects of vagal afferent- or efferent-selective stimulation on PD using continuous electrical stimulation remains to be determined., Objective: To investigate the effects of continuous and selective stimulation of vagal afferent or efferent fiber on Parkinsonian rats., Methods: Rats were divided into 5 group: intact VNS, afferent VNS (left VNS in the presence of left caudal vagotomy), efferent VNS (left VNS in the presence of left rostral vagotomy), sham, vagotomy. Rats underwent the implantation of cuff-electrode on left vagus nerve and 6-hydroxydopamine administration into the left striatum simultaneously. Electrical stimulation was delivered just after 6-OHDA administration and continued for 14 days. In afferent VNS and efferent VNS group, the vagus nerve was dissected at distal or proximal portion of cuff-electrode to imitate the selective stimulation of afferent or efferent vagal fiber respectively., Results: Intact VNS and afferent VNS reduced the behavioral impairments in cylinder test and methamphetamine-induced rotation test, which were accompanied by reduced inflammatory glial cells in substantia nigra with the increased density of the rate limiting enzyme in locus coeruleus. In contrast, efferent VNS did not exert any therapeutic effects., Conclusion: Continuous VNS promoted neuroprotective and anti-inflammatory effect in experimental PD, highlighting the crucial role of the afferent vagal pathway in mediating these therapeutic outcomes., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Mesenchymal stromal cell (MSC) transplantation therapy is a promising therapy for stroke patients. In parallel, rehabilitation with physical exercise could ameliorate stroke-induced neurological impairment. In this study, we aimed to clarify whether combination therapy of intracerebral transplantation of human modified bone marrow-derived MSCs, SB623 cells, and voluntary exercise with running wheel (RW) could exert synergistic therapeutic effects on a rat model of ischemic stroke., Methods: Wistar rats received right transient middle cerebral artery occlusion (MCAO). Voluntary exercise (Ex) groups were trained in a cage with RW from day 7 before MCAO. SB623 cells (4.0 × 10 5 cells/5 μl) were stereotactically injected into the right striatum at day 1 after MCAO. Behavioral tests were performed at day 1, 7, and 14 after MCAO using the modified Neurological Severity Score (mNSS) and cylinder test. Rats were euthanized at day 15 after MCAO for mRNA level evaluation of ischemic infarct area, endogenous neurogenesis, angiogenesis, and expression of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). The rats were randomly assigned to one of the four groups: vehicle, Ex, SB623, and SB623 + Ex groups., Results: SB623 + Ex group achieved significant neurological recovery in mNSS compared to the vehicle group (p < 0.05). The cerebral infarct area of SB623 + Ex group was significantly decreased compared to those in all other groups (p < 0.05). The number of BrdU/Doublecortin (Dcx) double-positive cells in the subventricular zone (SVZ) and the dentate gyrus (DG), the laminin-positive area in the ischemic boundary zone (IBZ), and the mRNA level of BDNF and VEGF in SB623 + Ex group were significantly increased compared to those in all other groups (p < 0.05)., Conclusions: This study suggests that combination therapy of intracerebral transplantation SB623 cells and voluntary exercise with RW achieves robust neurological recovery and synergistically promotes endogenous neurogenesis and angiogenesis after cerebral ischemia, possibly through a mechanism involving the up-regulation of BDNF and VEGF., (© 2023. The Author(s).)

Aims: SB623 cells are human bone marrow stromal cells transfected with Notch1 intracellular domain. In this study, we examined potential regenerative mechanisms underlying stereotaxic transplantation of SB623 cells in rats with experimental acute ischemic stroke., Methods: We prepared control group, empty capsule (EC) group, SB623 cell group (SB623), and encapsulated SB623 cell (eSB623) group. Transient middle cerebral artery occlusion (MCAO) was performed on day 0, and 24 h after MCAO, stroke rats received transplantation into the envisioned ischemic penumbra. Modified neurological severity score (mNSS) was evaluated, and histological evaluations were performed., Results: In the mNSS, SB623 and eSB623 groups showed significant improvement compared to the other groups. Histological analysis revealed that the infarction area in SB623 and eSB623 groups was reduced. In the eSB623 group, robust cell viability and neurogenesis were detected in the subventricular zone that increased significantly compared to all other groups., Conclusion: SB623 cells with or without encapsulation showed therapeutic effects on ischemic stroke. Encapsulated SB623 cells showed enhanced neurogenesis and increased viability inside the capsules. This study reveals the mechanism of secretory function of transplanted SB623 cells, but not cell-cell interaction as primarily mediating the cells' functional benefits in ischemic stroke., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Intensive care unit (ICU) survivors after traumatic brain injury (TBI) frequently have serious disabilities with subsequent difficulty in reintegration into society. We aimed to investigate outcomes for ICU survivors after moderate to severe TBI (msTBI) and to identify predictive factors of return home (RH) and return to work (RTW). This single-center retrospective cohort study was conducted on all trauma patients admitted to the emergency ICU of our hospital between 2013 and 2017. Of these patients, adult (age ≥ 18 years) msTBI patients with head Abbreviated Injury Scale ≥ 3 were extracted. We performed univariate/multivariate logistic regression analyses to explore the predictive factors of RH and RTW. Among a total of 146 ICU survivors after msTBI, 107 were included (median follow-up period: 26 months). The RH and RTW rates were 78% and 35%, respectively. Multivariate analyses revealed that the predictive factors of RH were age < 65 years (P < 0.001), HR < 76 bpm (P = 0.015), platelet count ≥ 19× 10 4 /μL (P = 0.0037), D-dimer < 26 μg/mL (P = 0.034), and Glasgow Coma Scale (GCS) score > 8 (P = 0.0015). Similarly, the predictive factors of RTW were age < 65 years (P < 0.001) and GCS score > 8 (P = 0.0039). This study revealed that "age" and "GCS score on admission" affected RH and RTW for ICU survivors after msTBI.

In the management of patients with craniosynostosis, it is important to understand growth curve of the normal cranium. Although three-dimensional (3D) computed tomography (CT) images taken in thin slices are easily available nowadays, data on the growth curves of intracranial volume (ICV), cranial length, cranial width, and cranial height in the normal cranium are mainly based on older studies using radiography, and there are insufficient reports using CT images especially taken in thin slices. The purpose of this study was to establish growth curves in the normal cranium of Japanese children using thin-slice images. Cranial images of 106 subjects (57 males, 49 females; aged 0-83 months) without significant cranial abnormalities were retrospectively analyzed. Using thin-slice CT images, the ICV and two-dimensional parameters such as cranial length, cranial width, and cranial height were measured by iPlan, followed by generating growth curves and calculating cephalic index (CI). ICV calculated from thin-slice CT images was compared with that obtained by substituting two-dimensional parameters into Mackinnon formula. The ICV growth curves for males and females were similar in shape. As with the ICV, the two-dimensional parameters increased most rapidly in the first year after birth. There was no significant difference in CI between the sexes or among any age groups. ICV calculated from thin-slice 3D CT images was 60% of that obtained from Mackinnon formula. These data will enable us to compare these specific measurements in craniosynostosis patients directly with those of normal children, which will hopefully help in managing these patients.

Background: The major surgical treatment for Parkinson's disease (PD) is deep brain stimulation (DBS), but a less invasive treatment is desired. Vagus nerve stimulation (VNS) is a relatively safe treatment without cerebral invasiveness. In this study, we developed a wireless controllable electrical stimulator to examine the efficacy of VNS on PD model rats., Methods: Adult female Sprague-Dawley rats underwent placement of a cuff-type electrode and stimulator on the vagus nerve. Following which, 6-hydroxydopamine (6-OHDA) was administered into the left striatum to prepare a PD model. VNS was started immediately after 6-OHDA administration and continued for 14 days. We evaluated the therapeutic effects of VNS with behavioral and immunohistochemical outcome assays under different stimulation intensity (0.1, 0.25, 0.5 and 1 mA)., Results: VNS with 0.25-0.5 mA intensity remarkably improved behavioral impairment, preserved dopamine neurons, reduced inflammatory glial cells, and increased noradrenergic neurons. On the other hand, VNS with 0.1 mA and 1 mA intensity did not display significant therapeutic efficacy., Conclusions: VNS with 0.25-0.5 mA intensity has anti-inflammatory and neuroprotective effects on PD model rats induced by 6-OHDA administration. In addition, we were able to confirm the practicality and effectiveness of the new experimental device.

Background: Spinal cord stimulation (SCS) exerts neuroprotective effects in animal models of Parkinson's disease (PD). Conventional stimulation techniques entail limited stimulation time and restricted movement of animals, warranting the need for optimizing the SCS regimen to address the progressive nature of the disease and to improve its clinical translation to PD patients., Objective: Recognizing the limitations of conventional stimulation, we now investigated the effects of continuous SCS in freely moving parkinsonian rats., Methods: We developed a small device that could deliver continuous SCS. At the start of the experiment, thirty female Sprague-Dawley rats received the dopamine (DA)-depleting neurotoxin, 6-hydroxydopamine, into the right striatum. The SCS device was fixed below the shoulder area of the back of the animal, and a line from this device was passed under the skin to an electrode that was then implanted epidurally over the dorsal column. The rats were divided into three groups: control, 8-h stimulation, and 24-h stimulation, and behaviorally tested then euthanized for immunohistochemical analysis., Results: The 8- and 24-h stimulation groups displayed significant behavioral improvement compared to the control group. Both SCS-stimulated groups exhibited significantly preserved tyrosine hydroxylase (TH)-positive fibers and neurons in the striatum and substantia nigra pars compacta (SNc), respectively, compared to the control group. Notably, the 24-h stimulation group showed significantly pronounced preservation of the striatal TH-positive fibers compared to the 8-h stimulation group. Moreover, the 24-h group demonstrated significantly reduced number of microglia in the striatum and SNc and increased laminin-positive area of the cerebral cortex compared to the control group., Conclusions: This study demonstrated the behavioral and histological benefits of continuous SCS in a time-dependent manner in freely moving PD animals, possibly mediated by anti-inflammatory and angiogenic mechanisms., (Copyright © 2020 Kuwahara, Sasaki, Yasuhara, Kameda, Okazaki, Hosomoto, Kin, Okazaki, Yabuno, Kawauchi, Tomita, Umakoshi, Kin, Morimoto, Lee, Tajiri, Borlongan and Date.)

Background: Acute ischemic stroke caused by cervical internal carotid artery stenosis (ICS) with altered consciousness and progressive paralysis leads to a poor neurologic prognosis. When such a patient is brought to the hospital in the hyperacute phase, intravenous tissue plasminogen activator is first administered. However, when an indwelling carotid artery stent is required after administration, physicians often hesitate to use antithrombotic drugs. In this report, we propose performing staged angioplasty (SAP) for such cases., Methods: Four patients were retrospectively investigated. In all 4 patients, we immediately performed only percutaneous transluminal angioplasty (PTA) without antiplatelet drugs. If both cerebral perfusion on angiography and neurologic findings improved, no additional treatment was provided; otherwise, emergency carotid artery stenting (eCAS) was performed. In PTA-successful cases, eCAS or carotid endarterectomy (CEA) was performed with single or dual antiplatelet drugs at a later date., Results: The success rate of PTA was 50% (2 of 4), and the overall treatment success rate was 100% (4 of 4). Three patients had favorable outcomes (modified Rankin Scale [mRS] score 0-2), but unfortunately, 1 patient had severe disability (mRS score >3) on discharge. The PTA-successful patients had no perioperative complications. On the other hand, 1 of the 2 patients who underwent eCAS experienced embolic complications, including distal embolization., Conclusions: In this investigation, both eCAS and SAP could be performed safety. However, performing SAP first without antiplatelet drugs to avoid hemorrhagic complications and cerebral hyperperfusion syndrome appears to have considerable validity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: In surgical treatment of acute subdural hematoma (ASDH), neurosurgeons frequently encounter bleeding from cortical arteries, which is usually controlled with bipolar coagulation. However, bipolar coagulation is associated with a risk of sacrificing the cortical artery, which may affect the prognosis of neurological symptoms when these cortical arteries supply critical areas. In this article, we describe microsurgical repair of damaged cortical arteries using a 10-0 nylon micro-suture in patients with arterial-origin ASDH., Methods: After removal of the subdural hematoma, the exact bleeding point of the cortical artery was identified, and the 10-0 nylon suture stitches were placed on the arterial tear under a microscope. After completion of the micro-suture, vascular patency was confirmed by indocyanine green (ICG) videoangiography., Results: From June 2015 through February 2017, microsurgical repair was performed for seven cortical arteries in six patients. All damaged arteries were located near the Sylvian fissure, and all tears were pinhole tears. The average blood flow occlusion time was 8 min (range, 0-15 min). The patency of all seven repaired arteries was successfully confirmed by ICG videoangiography. Postoperative cerebral infarction was not observed except in one patient with cerebral contusion and a history of severe head trauma., Conclusions: The present report demonstrates that repair of a cortical artery by the 10-0 nylon micro-suture is a simple and safe method with a low risk of sacrificing the artery. This technique may be a good option in the surgical treatment of arterial-origin ASDH, especially when the accompanying cerebral contusion is minimal.

In Japan, hepatic arterial infusion chemotherapy (HAIC) using reservoir system is recommended for patients with hepatocellular carcinoma (HCC) whose hepatic spare ability is favorable. Arterial infusion catheter is commonly detained in hepatic artery via femoral or brachial artery. In our hospital, catheter is often inserted by puncturing the left subclavian or brachial artery considering the patient's activities of daily living (ADL) during long-term detaining. However, it rarely causes posterior circulation ischemic stroke because of the left vertebral artery branches on the path of catheter. We herein report a case of posterior circulation ischemic stroke caused by heparin-induced thrombosis (HIT) after detaining hepatic arterial infusion catheter. A 63-year-old man who is under HAIC treatment for HCC was introduced to the department of neurological surgery because of vertigo and vomiting. Magnetic resonance imaging revealed sporadic fresh cerebral infarction in the bilateral cerebellar hemisphere. Carotid ultrasonography detected a floating thrombus around the part of the left vertebral subclavian artery bifurcation. Detained catheter was removed and continuous heparin administration was started immediately. However, thrombocytopenia occurred 5 days after the injection. Because 4T's score was 6 points, HIT was strongly suspected. We stopped heparin injection immediately and observed the patient's physical status strictly. After that, platelet value improved naturally. At the late date, antibodies specific for platelet factor 4/heparin complexes were positive and he was diagnosed with HIT., (Copyright © 2018. Published by Elsevier Inc.)

Transglycosylation activity of endo-beta-N-acetylglucosaminidase HS (Endo HS) was investigated using native human transferrin as a donor of an asparagine-linked oligosaccharide and p-nitrophenyl-beta-d-glucose (PNP-beta-d-Glc) as an acceptor of the oligosaccharide. The amount of the product increased dependent on the concentration of the acceptors. Absorption spectrum, exoglycosidase digestion and matrix assisted laser desorption and ionization-time of flight (MALDI-TOF) mass analysis of the transglycosylation product indicated that the asialobiantennary complex type oligosaccharide of human transferrin was transferred to PNP-beta-d-Glc. Endo HS also transferred the oligosaccharide of human transferrin to PNP-alpha-d-Glc, PNP-alpha-d-Gal, PNP-beta-d-Gal, PNP-beta-d-Man, PNP-beta-d-Xyl, PNP-beta-d-GlcNAc, and PNP-glycerol at a different rate. No apparent difference in the K(m) value for human transferrin as an oligosaccharide donor was observed using different acceptors, PNP-beta-d-Glc and PNP-glycerol. The amount of the transglycosylation product successively increased and became constant and then very slightly decreased during the course of enzyme reaction. Endo HS was also transferred the triantennary complex type oligosaccharide of calf fetuin and the bi-, tri-, and tetrantennary complex type oligosaccharides of human alpha(1)-acid glycoprotein to PNP-beta-d-Glc. Furthermore, Endo HS transferred an asparagine-linked oligosaccharide from a hen egg glycopeptide to PNP-beta-d-Glc. The results demonstrate that Endo HS can transfer a wide variety of asparagine-linked complex type oligosaccharides to various monosaccharides. Endo HS was distinct from other enzymes in the specificity for oligosaccharide donors and acceptors.