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Summary: Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality, and its severity is closely related to the short-term prognosis of SAH patients. S100 calcium-binding protein A9 (S100A9) has been shown to be associated with some neurological diseases. In this study, the concentration of S100A9 in clinical cerebrospinal fluid samples was detected by enzyme-linked immunosorbent assay (ELISA), and the relationship between S100A9 and the prognosis of patients was explored. In addition, WT mice and S100A9 knockout mice were used to establish an in vivo SAH model. Neurological scores, brain water content, and histopathological staining were performed after a specified time. A co-culture model of BV2 and HT22 cells was treated with heme chloride to establish an in vitro SAH model. Our study confirmed that the expression of S100A9 protein in the CSF of SAH patients is increased, and it is related to the short-term prognosis of SAH patients. S100A9 protein is highly expressed in microglia in the central nervous system. S100A9 gene knockout significantly improved neurological function scores and reduced neuronal apoptosis. S100A9 protein can activate TLR4 receptor, promote nuclear transcription of NF-κB, increase the activation of inflammatory body, and ultimately aggravate nerve injury.

Introduction: Spontaneous subarachnoid hemorrhage (SAH), is a disorder that may be fatal and is primarily caused by a ruptured brain aneurysm. Despite significant leaps forward in the methods to produce aneurysms, the long-term outcomes did not much improve. Pioglitazone is a medication that has been authorized by the FDA as an agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone or PPARγ has neuroprotective benefits in animal experiments both during and after traumatic brain injury (TBI) and SAH. Nevertheless, the treatment impact of Pioglitazone on humans is still unknown at this time. As a result, we will conduct a randomized, double-blind, placebo-controlled trial to explore the impact of pioglitazone on SAH.Methods/Design: This trial will recruit 400 patients with SAH from four Chinese hospitals. These patients will be equally and randomly assigned to Pioglitazone and placebo control groups for up to 30 days. Scores on the modified Rankin scale (mRS) are the primary outcomes. The secondary outcomes are a 30-day all-cause mortality rate, 6 months of Montreal cognitive assessment (Mo-CA), delayed cerebral ischemia, the requirement for intensive care, the incidence of sepsis, etc. All serious adverse events (SAEs) were recorded during the hospital. Every primary and safety analysis was conducted based on the intention-to-treat technique. The participants were given either a matching placebo or 15 mg of pioglitazone, with dose titrated to a target of 45 mg daily. Data on the therapeutic use of pioglitazone after SAH will be provided as a consequence of the findings of this experiment. In addition, this pilot trial is the first to prospectively investigate the effectiveness and safety of pioglitazone in patients with SAH.Ethics and dissemination: Ethics approval was obtained from the Medical Ethics Committee of 904th Hospital of Joint Logistic Support Force of PLA (Wuxi Taihu Hospital, approval No. 20220701). The findings of the trial will be presented at conferences, discussed in relevant patient groups, and published in peer-reviewed journals.Clinical Trial Registration:clinicaltrials.gov, identifier ChiCTR2200062954.

C-X-C chemokine receptor type 4 (CXCR4) is critical for homeostasis of the adaptive and innate immune system in some CNS diseases. Bruton's tyrosine kinase (BTK) is an essential kinase that regulates inflammation in immune cells through multiple signaling pathways. This study aims to explore the effect of CXCR4 and BTK on neuroinflammation in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Our results showed that the expression of CXCR4 and p-BTK increased significantly at 24 h after SAH in vivo and in vitro. Ibrutinib improved neurological impairment, BBB disruption, cerebral edema, lipid peroxidation, neuroinflammation and neuronal death at 24 h after SAH. Inhibition of BTK phosphorylation promoted the in vitro transition of hemin-treated proinflammatory microglia to the anti-inflammatory state, inhibited the p-P65 expression and microglial pyroptosis. NLRP3 deficiency can significantly reduce pyroptosis in SAH mice. Moreover, CXCR4 inhibition can suppress NLRP3-mediated pyroptosis, NF-κB activation and NOX2 expression in vitro, and ibrutinib can abolish CXCR4-aggravated BBB damage and pyroptosis in EBI after SAH. The levels of CXCR4 in CSF of SAH patients is significantly increased, and it is positively correlated with GSDMD and IL-1β levels, and have a moderate diagnostic value for outcome at 6-month follow-up. Our findings revealed the effect of CXCR4 and P-BTK on NLRP3-mediated pyroptosis and lipid peroxidation after SAH in vivo and in vitro, and the potential diagnostic role of CXCR4 in CSF of SAH patients. Inhibition of CXCR4-BTK axis can significantly attenuate NLRP3-mediated pyroptosis and lipid peroxidation by regulating NF-κB activation in EBI after SAH.

Mesenchymal stem cells (MSCs) are promising seed cells for neural regeneration therapy owing to their plasticity and accessibility. They possess several inherent characteristics advantageous for the transplantation-based treatment of neurological disorders, including neural differentiation, immunosuppression, neurotrophy, and safety. However, the therapeutic efficacy of MSCs alone remains unsatisfactory in most cases. To improve some of their abilities, many studies have employed genetic engineering to transfer key genes into MSCs. Both viral and nonviral methods can be used to overexpress therapeutic proteins that complement the inherent properties. However, to date, different modes of gene transfer have specific drawbacks and advantages. In addition, MSCs can be functionalized through targeted gene modification to facilitate neural repair by promoting neural differentiation, enhancing neurotrophic and neuroprotective functions, and increasing survival and homing abilities. The methods of gene transfer and selection of delivered genes still need to be optimized for improved therapeutic and targeting efficacies while minimizing the loss of MSC function. In this review, we focus on gene transport technologies for engineering MSCs and the application of strategies for selecting optimal delivery genes. Further, we describe the prospects and challenges of their application in animal models of different neurological lesions to broaden treatment alternatives for neurological diseases.

Human dental pulp stem cells (hDPSCs) promote recovery after ischemic stroke; however, the therapeutic efficacy is limited by the poor survival of transplanted cells. For in vitro experiments in the present study, we used oxygen-glucose deprivation/reoxygenation in hDPSCs to mimic cell damage induced by ischemia/reperfusion. We found that miRNA-34a-5p (miR-34a) was elevated under oxygen-glucose deprivation/reoxygenation conditions in hDPSCs. Inhibition of miR-34a facilitated the proliferation and antioxidant capacity and reduced the apoptosis of hDPSCs. Moreover, dual-luciferase reporter gene assay showed WNT1 and SIRT1 as the targets of miR-34a. In miR-34a knockdown cell lines, WNT1 suppression reduced cell proliferation, and SIRT1 suppression decreased the antioxidant capacity. Together, these results indicated that miR-34a regulates cell proliferation and antioxidant stress via targeting WNT1 and SIRT1, respectively. For in vivo experiments, we injected genetically modified hDPSCs (anti34a-hDPSCs) into the brains of mice. We found that anti34a-hDPSCs significantly inhibited apoptosis, reduced cerebral edema and cerebral infarct volume, and improved motor function in mice. This study provides new insights into the molecular mechanism of the cell proliferation and antioxidant capacity of hDPSCs, and suggests a potential gene that can be targeted to improve the survival rate and efficacy of transplanted hDPSCs in brain after ischemic stroke.

Abstract Background Neuroinflammation and neuronal apoptosis are closely associated with a poor prognosis in patients with subarachnoid hemorrhage (SAH). We investigated the role of C–C motif chemokine receptor 2 (CCR2) in SAH. Methods Pre-processed RNA-seq transcriptome datasets GSE167110 and GSE79416 from the Gene Expression Omnibus (GEO) database were screened for genes differentially expressed between mice with SAH and control mice, using bioinformatics analysis. The endovascular perforation model was performed to establish SAH. RS504393 (a CCR2 antagonist) and LY294002 (PI3K inhibitor) were administered to explore the mechanism of neuroinflammation after SAH. SAH grading, neurological scoring, brain water content and blood–brain barrier (BBB) permeability determination, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence were performed. An in vitro model of SAH was induced in H22 cells by hemin treatment. The protective mechanism of CCR2 inhibition was studied by adding RS504393 and LY294002. Clinical cerebrospinal fluid (CST) samples were detected by ELISA. Results Expression of CCR2 was upregulated in both datasets and was identified as a hub gene. CCR2 expression was significantly upregulated in the cytoplasm of neurons after SAH, both in vitro and in vivo. RS significantly reduced the brain water content and blood–brain barrier permeability, alleviated neuroinflammation, and reduced neuronal apoptosis after SAH. Additionally, the protective effects of CCR2 inhibition were abolished by LY treatment. Finally, the levels of CCR2, inflammatory factors, and apoptotic factors were elevated in the CSF of patients with SAH. CCR2 levels were associated with patient outcomes at the 6-month follow-up. Conclusion CCR2 expression was upregulated in both in vitro and in vivo SAH models. Additionally, inhibition of CCR2, at least partly through the PI3K/AKT pathway, alleviated neuroinflammation and neuronal apoptosis in vivo and in vitro. CCR2 levels in the CSF have a moderate diagnostic value for 6-month outcome prediction in patients with SAH.

Stem cell therapy is of great therapeutical potential for anti-aging treatment. Lysates of dental pulp stem cells (DPSC) are rich in numerous cytokines, which can improve the cell growth environment and enhance collagen synthesis in the skin. Frequently, the instability of protein growth factors severely restricts their applications in living systems. In this study, a strategy for delivering the growth factors of DPSC lysate via protein-encapsulated zeolitic imidazolate framework-8 (ZIF-8) nanoparticles was developed. Using ZIF-8 as protein-encapsulated nanoparticles, a ZIF-8@DPSC lysate (ZIF-8@DL) with pH-responsive drug release was produced. ZIF-8@DL demonstrated superior cutaneous uptake, cutaneous penetration, and retention capacity in vivo compared to DPSC lysate. Moreover, ZIF-8@DL demonstrated excellent in vitro and in vivo biocompatibility. Subcutaneous microneedle injection of ZIF-8@DL into a mouse photoaging model resulted in significantly improved epidermal thickness, dermal collagen deposition, and cutaneous inflammation, with no apparent adverse effects. This study provides a safe and efficient method for enhancing the therapeutic application of DPSC lysate. It has the potential to expedite the clinical implementation of lysate-based anti-photoaging therapy.

Subarachnoid haemorrhage (SAH) is a common cerebrovascular disease with high disability and mortality rates worldwide. The pathophysiological mechanisms involved in an aneurysm rupture in SAH are complex and can be divided into early brain injury and delayed brain injury. The initial mechanical insult results in brain tissue and vascular disruption with hemorrhages and neuronal necrosis. Following this, the secondary injury results in diffused cerebral damage in the peri-core area. However, the molecular mechanisms of neuronal death following an aneurysmal SAH are complex and currently unclear. Furthermore, multiple cell death pathways are stimulated during the pathogenesis of brain damage. Notably, particular attention should be devoted to necrosis, apoptosis, autophagy, necroptosis, pyroptosis and ferroptosis. Thus, this review discussed the mechanism of neuronal death and its influence on brain injury after SAH.

BackgroundPredicting rupture risk is important for aneurysm management. This research aimed to develop and validate a nomogram model to forecast the rupture risk of posterior communicating artery (PcomA) aneurysms.MethodsClinical, morphological, and hemodynamic parameters of 107 unruptured PcomA aneurysms and 225 ruptured PcomA aneurysms were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) analysis was applied to identify the optimal rupture risk factors, and a web-based dynamic nomogram was developed accordingly. The nomogram model was internally validated and externally validated independently. The receiver operating characteristic (ROC) curve was used to assess the discrimination of nomogram, and simultaneously the Hosmer–Lemeshow test and calibration plots were used to assess the calibration. Decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical utility of nomogram additionally.ResultsFour optimal rupture predictors of PcomA aneurysms were selected by LASSO and identified by multivariate logistic analysis, including hypertension, aspect ratio (AR), oscillatory shear index (OSI), and wall shear stress (WSS). A web-based dynamic nomogram was then developed. The area under the curve (AUC) in the training and external validation cohorts was 0.872 and 0.867, respectively. The Hosmer–Lemeshow p > 0.05 and calibration curves showed an appropriate fit. The results of DCA and CIC indicated that the net benefit rate of the nomogram model is higher than other models.ConclusionHypertension, high AR, high OSI, and low WSS were the most relevant risk factors for rupture of PcomA aneurysms. A web-based dynamic nomogram thus established demonstrated adequate discrimination and calibration after internal and external validation. We hope that this tool will provide guidance for the management of PcomA aneurysms.

Objectives: This study aimed to identify and evaluate the intracranial transplantation of dental pulp stem cells (DPSCs) as a possible ischemic stroke therapy that mitigates neuronal death/apoptosis. Materials and methods: DPSCs were isolated from the impacted third molars of healthy volunteers and then intracranially injected at 24 h post-ischemic stroke to Sprague Dawley rats that had been subjected to 2 h of middle cerebral artery occlusion. Neurological functional deficits were assessed using the modified neurological severity score (mNSS), and cerebral edema was quantified using brain water content. Neuronal death/apoptosis was indicated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, NeuN immunofluorescence and immunohistochemistry, and Western blot analysis of the protein expression of anti-apoptotic indicator of Bcl-2 and apoptotic indicators of Bax and caspase 3. Results: DPSC transplantation could ameliorate neurological dysfunction and brain edema, reduce infarct volume, decrease the percentage of TUNEL-positive nuclei, increase the number and percentage of NeuN-positive cells in ischemic penumbra, increase the ratio of Bcl-2 and Bax and down-regulate the production of caspase 3 in the cortical infarct zone. Conclusions: DPSC therapy via intracranial injection exerted remarkably neuroprotection mainly by inhibiting neuronal death/apoptosis.

Salt tolerance is one of the most important problems in the field of environmental governance and restoration. Among the various sources of factors, except temperature, salinity is a key factor that interrupts bacterial growth significantly. In this regard, constant efforts are made for the development of salt-tolerant strains, but few strains with salt tolerance, such as Terribacillus saccharophilus, were found, and there are still few relevant reports about their salt tolerance from complete genomic analysis. Furthermore, with the development of the economy, environmental pollution caused by oil exploitation has attracted much attention, so it is crucial to find the bacteria from T. saccharophilus which could degrade petroleum hydrocarbon even under high-salt conditions. Herein, one T. saccharophilus strain named ZY-1 with salt tolerance was isolated by increasing the salinity on LB medium step by step with reservoir water as the bacterial source. Its complete genome was sequenced, which was the first report of the complete genome for T. saccharophilus species with petroleum hydrocarbon degradation and emulsifying properties. In addition, its genome sequences were compared with the other five strains that are from the same genus level. The results indicated that there really exist some differences among them. In addition, some characteristics were studied. The salt-tolerant strain ZY-1 developed in this study and its emulsification and degradation performance of petroleum hydrocarbons were studied, which is expected to widely broaden the research scope of petroleum hydrocarbon-degrading bacteria in the oil field environment even in the extreme environment. The experiments verified that ZY-1 could significantly grow not only in the salt field but also in the oil field environment. It also demonstrated that the developed salt-tolerant strain can be applied in the petroleum hydrocarbon pollution field for bioremediation. In addition, we expect that the identified variants which occurred specifically in the high-salt strain will enhance the molecular biological understanding and be broadly applied to the biological engineering field.

BackgroundTimely and accurate prediction of delayed cerebral ischemia is critical for improving the prognosis of patients with aneurysmal subarachnoid hemorrhage. Machine learning (ML) algorithms are increasingly regarded as having a higher prediction power than conventional logistic regression (LR). This study aims to construct LR and ML models and compare their prediction power on delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH).MethodsThis was a multicenter, retrospective, observational cohort study that enrolled patients with aneurysmal subarachnoid hemorrhage from five hospitals in China. A total of 404 aSAH patients were prospectively enrolled. We randomly divided the patients into training (N = 303) and validation cohorts (N = 101) according to a ratio of 75–25%. One LR and six popular ML algorithms were used to construct models. The area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, confusion matrix, sensitivity, specificity, calibration curve, and Hosmer–Lemeshow test were used to assess and compare the model performance. Finally, we calculated each feature of importance.ResultsA total of 112 (27.7%) patients developed DCI. Our results showed that conventional LR with an AUC value of 0.824 (95%CI: 0.73–0.91) in the validation cohort outperformed k-nearest neighbor, decision tree, support vector machine, and extreme gradient boosting model with the AUCs of 0.792 (95%CI: 0.68–0.9, P = 0.46), 0.675 (95%CI: 0.56–0.79, P < 0.01), 0.677 (95%CI: 0.57–0.77, P < 0.01), and 0.78 (95%CI: 0.68–0.87, P = 0.50). However, random forest (RF) and artificial neural network model with the same AUC (0.858, 95%CI: 0.78–0.93, P = 0.26) were better than the LR. The accuracy and the balanced accuracy of the RF were 20.8% and 11% higher than the latter, and the RF also showed good calibration in the validation cohort (Hosmer-Lemeshow: P = 0.203). We found that the CT value of subarachnoid hemorrhage, WBC count, neutrophil count, CT value of cerebral edema, and monocyte count were the five most important features for DCI prediction in the RF model. We then developed an online prediction tool (https://dynamic-nomogram.shinyapps.io/DynNomapp-DCI/) based on important features to calculate DCI risk precisely.ConclusionsIn this multicenter study, we found that several ML methods, particularly RF, outperformed conventional LR. Furthermore, an online prediction tool based on the RF model was developed to identify patients at high risk for DCI after SAH and facilitate timely interventions.Clinical Trial Registrationhttp://www.chictr.org.cn, Unique identifier: ChiCTR2100044448.

ObjectiveThis study aimed to determine the ruptured rate and hemodynamic difference between wide-neck aneurysms (WNAs) and narrow-neck aneurysms (NNAs), as well as the hemodynamic parameters of risk factors for aneurysm rupture.MethodsA total of 121 cases of intracranial aneurysms (IAs) were studied retrospectively between January 2019 and April 2021 at Renmin Hospital of Wuhan University. Intracranial aneurysms were classified into four types: ruptured wide-neck aneurysms (RWNAs), unruptured wide-neck aneurysms (UWNAs), ruptured narrow-neck aneurysms (RNNAs), and unruptured narrow-neck aneurysms (UNNAs). The Chi-square test was used to compare differences in rupture ratios. The clinical characteristics and hemodynamics were analyzed statistically to reveal the rupture risk factors. Moreover, significant parameters were subjected to binary logistic regression analysis to identify the independent predictive factors. The receiver operating characteristic (ROC) curve was performed to obtain cutoff values.ResultsWNAs ruptured more frequently than NNAs (P = 0.033). Ruptured intracranial aneurysms (RIAs) were characterized by significantly higher intra-aneurysmal pressure (IAP), wall shear stress (WSS), wall shear stress gradient (WSSG), and lower normalized wall shear stress (NWSS) than unruptured intracranial aneurysms (UIAs). RWNAs had higher IAP, WSS, and lower NWSS than UWNAs (P < 0.05). RNNAs had higher IAP, Streamwise WSSG and lower NWSS compared to UNNAs (P < 0.05). Binary logistic regression revealed that IAP and WSS were independent predictive risk factors for WNAs rupture, with cut-off values of 405.5 and 6.66 Pa, respectively. Also, IAP was an independent predictive risk factor for NNA rupture, with a cut-off value of 255.3 Pa.ConclusionsWide-neck aneurysms and narrow-neck aneurysms have diverse hemodynamics, which prompts a higher rupture ratio for WNAs. IAP could characterize the rupture risk in both WNAs and NNAs independently, but WSS could only predict the rupture risk in WNAs. This research might assist neurosurgeons with fostering a more sensible strategy for the treatment of IAs.

Brainstem hemorrhage (mainly pontine hemorrhage caused by hypertension) has the clinical characteristics of acute onset, rapid progress, high mortality, and high disability rate. Due to the complexity of the brainstem’s anatomical structure and functional importance, it is generally recognized that brainstem treatment is difficult and risky, so it has been regarded as a restricted area of surgery. However, in recent years, continuous progress is being made in many areas, including microsurgical technology, stereotactic technology, robot-assisted surgery, neuroendoscopy, and theoretical and clinical practice of neurorestoration, aiding in the understanding, diagnosis, and treatment of brainstem hemorrhage injuries. The Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) organized relevant experts to formulate this clinical guideline to diagnose and restore damaged nerves after brainstem hemorrhages, promote a standardized diagnosis, and to neurorestoratologically treat this disease.

Ischemic stroke is a serious cerebral disease that often induces death and long-term disability. As a currently available therapy for recanalization after ischemic stroke, thrombolysis, including intravenous thrombolysis and endovascular therapy, still cannot be applicable to all patients due to the narrow time window. Mesenchymal stem cell (MSC) transplantation therapy, which can trigger neuronal regeneration and repair, has been considered as a significant advance in treatment of ischemic stroke. MSC transplantation therapy has exhibited its potential to improve the neurological function in ischemic stroke. Our review describes the current progress and future perspective of MSC transplantation therapy in ischemic stroke treatment, including cell types, transplantation approaches, therapeutic mechanisms, and preliminary clinical trials of MSC transplantation, for providing us an update role of MSC transplantation in ischemic stroke treatment.

Anterior communicating artery aneurysms account for 23–40% of ruptured intracranial aneurysms and 12–15% of unruptured aneurysms and are the most common intracranial ruptured or unruptured aneurysms. Because they have relatively complex anatomical structures and anatomical variations and are adjacent to important blood vessels and structures, in the process of microsurgical exposure of an Anterior communicating artery aneurysm, attention should be paid not only to the anatomical characteristics of the aneurysm itself but also to the adjacent important blood vessels and perforating arteries; therefore, both surgical clipping and endovascular embolization are serious challenges for neurosurgeons. No matter which treatment is chosen, it is necessary to determine the structure of the Anterior communicating artery and its perforating arteries as well as whether there is a fenestration deformity of the Anterior communicating artery and the relationship between bilateral A1-A2 before surgery. The shape and size of the aneurysm itself and its location relative to adjacent blood vessels also need to be considered to better complete the procedure, and this is especially true for microsurgical clipping. Clarifying the anatomy before surgery is helpful for better selecting the surgical approach and surgical side, which could affect the intraoperative exposure of the aneurysm and adjacent arteries, the surgical difficulty, the resection rate, and the postoperative complications. Therefore, starting with Anterior communicating artery aneurysms and their adjacent structures and variations, this paper reviews the latest progress in surgical treatment based on anatomic specificity as well as the most recent clinical studies.

Acute central nervous system (CNS) disease is very common and with high mortality. Many basic studies have confirmed the molecular mechanism of early brain injury (EBI) after acute CNS disease. Neuron death and dysfunction are important reasons for the neurological dysfunction in patients with acute CNS disease. Ferroptosis is a nonapoptotic form of cell death, the classical characteristic of which is based on the iron-dependent accumulation of toxic lipid reactive oxygen species. Previous studies have indicated that this mechanism is critical in the cell death events observed in many diseases, including cancer, tumor resistance, Alzheimer’s disease, Parkinson’s disease, stroke, and intracerebral hemorrhage (ICH). Ferroptosis may also play a very important role in EBI after acute CNS disease. Unresolved issues include the relationship between ferroptosis and other forms of cell death after acute CNS disease, the specific molecular mechanisms of EBI, the strategies to activate or inhibit ferroptosis to achieve desirable attenuation of EBI, and the need to find new molecular markers of ferroptosis that can be used to detect and study this process in vivo after acute CNS disease.

Background: Experimental evidence has indicated the benefits of intraoperative controlled decompression for the treatment of severe traumatic brain injury (sTBI). Intraoperative rapid decompression (conventional decompression) for the treatment of sTBI may result in intra- and post-operative complications. Controlled decompression may reduce these complications. Previous clinical trials in China have not yielded conclusive results regarding controlled decompression for sTBI. Therefore, we explored whether controlled decompression treatment decreases the rates of complications and improves the outcomes of patients with sTBI.Methods: We performed this randomized, controlled trial at our hospital. Patients with sTBI aged 18–75 years old were randomly (1:1) divided into controlled decompression surgery (n = 124) or rapid decompression surgery groups (n = 124). The primary outcome measures were the Extended Glasgow Outcome Scale (GOS-E) score at 6 months and 30-days all-cause mortality. The secondary outcomes were the incidences of intraoperative brain swelling, post-traumatic cerebral infarction, and delayed hematoma.Results: Compared with the rapid decompression group, the controlled decompression group had reduced 30-days all-cause mortality (18.6 vs. 30.8%, P = 0.035) and improved the 6-months GOS-E scores, and the difference was significant. In addition, the patients in the controlled decompression group had a lower intraoperative brain swelling rate (13.3 vs. 24.3%, P = 0.036), a lower delayed hematoma rate (17.7 vs. 29.0%, P = 0.048) and a relatively lower post-traumatic cerebral infarction rate (15.0 vs. 22.4%, P = 0.127) than those in the rapid decompression group.Conclusions: Our data suggest that controlled decompression surgery significantly improves sTBI outcomes and decreases the rates of sTBI-related complications. However, this was a single-hospital study, and well-designed multicenter randomized controlled trials are needed to evaluate the effects of controlled decompression surgery for the management of patients with sTBI.Clinical Trial Registration: Chinese Clinical Trial Registry; Date: 14/Dec/2013; Number: ChiCTR-TCC-13004002.

Previous studies have indicated that 2,2′-dipyridyl, a lipid-soluble ferrous iron chelator, can reduce brain injury after cerebral ischemia and reduce cerebral vasospasm after subarachnoid hemorrhage. In this study, we examined the efficacy of 2,2′-dipyridyl after intracerebral hemorrhage (ICH) in 12-month-old mice. ICH was modeled by intrastriatal injection of collagenase or autologous whole blood. 2,2′-Dipyridyl or vehicle was administered intraperitoneally 2 h before ICH (pretreatment) or 6 h after ICH (post-treatment) and then once daily for up to 3 days. Mice in the pretreatment group were sacrificed 1 or 3 days after ICH and examined for iron deposition, neuronal death, oxidative stress, microglial/astrocyte activation, neutrophil infiltration, and white matter damage. Mice in the post-treatment group were examined for brain lesion volume and edema on day 3 and for neurologic deficits on days 1, 3, and 28 after ICH. Pretreatment with 2,2′-dipyridyl decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, reduced microglial activation without affecting astrocytes or neutrophil infiltration, and attenuated white matter damage. Post-treatment reduced brain lesion volume and edema and improved neurologic function. These results indicate that the lipid-soluble ferrous iron chelator 2,2′-dipyridyl can reduce brain injury and improve functional outcome after ICH.

Tissue plasminogen activator (tPA) remains the only approved thrombolytic agent for the early treatment of ischemic stroke. However, treatment with tPA may lead to disruption of the blood–brain barrier and hemorrhagic transformation. 17β-estradiol (E2) has demonstrated efficacy in reduction of infarct volume in ischemic stroke models. The effects of acute administration of E2 on permeability of the blood–brain barrier and its ability to prevent hemorrhagic transformation in ischemic rats treated with tPA have not previously been studied. Here, we show that neurological deficits, brain water content, and Evan's blue extravasation were increased in ovariectomized female Wistar rats treated with tPA and attenuated in rats receiving E2+tPA. We also show that intracerebral hemoglobin and matrix metalloproteinase-9 activity were elevated with tPA treatment, and these increases were reduced by E2 treatment. Taken together, these data demonstrate that acute administration of E2 is capable of ameliorating some of the adverse effects of tPA administration, including the increase of matrix metalloproteinase-9 activity, blood–brain barrier permeability, and hemorrhagic transformation. These findings suggest a potential role for estrogen in thrombolytic treatment for ischemic stroke.