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Cerebral ischemia/reperfusion (IR) after ischemic stroke causes deleterious microglial activation. Protein tyrosine phosphatase 1B (PTP1B) exacerbates neuroinflammation, yet the effect of the inhibition on microglial activation and cerebral IR injury is unknown. A cerebral IR rat model was induced by middle cerebral artery occlusion (MCAO) and reperfusion. The PTP1B inhibitor, sc-222227, was administered intracerebroventricularly. Neurologic deficits, infarct volume, and brain water content were examined. An in vitro oxygen glucose deprivation/reoxygenation (OGD/R) model was established in primary microglia and BV-2 cells. Microglial activation/polarization, endoplasmic reticulum (ER) stress, autophagy, and apoptosis were detected using western blot, immunohistology, ELISA, and real-time PCR. Protein interaction was assessed by a proximity ligation assay. The results showed a significant increase in microglial PTP1B expression after IR injury. Sc-222227 attenuated IR-induced microglial activation, ER stress, and autophagy and promoted M2 polarization. Upon OGD/R, sc-222227 mitigated microglial activation by inhibiting ER stress-dependent autophagy, the effect of which was abolished by PERK activation, and PERK inhibition attenuated microglial activation. The PTP1B-phosphorylated PERK protein interaction was significantly increased after OGD/R, but decreased upon sc-222227 treatment. Finally, sc-222227 mitigated neuronal damage and neurologic deficits after IR injury. Treatment targeting microglial PTP1B might be a potential therapeutic strategy for ischemic stroke treatment.

Background This meta-analysis aimed to evaluate the risk of shunt-dependent hydrocephalus among patients with ruptured intracranial aneurysms treated with either coil placement or clipping. Methods A systematic literature search of Embase, PubMed, Web of Science, and the Cochrane Library was performed to confirm relevant studies. The scientific literature was screened in accordance with the predetermined inclusion and exclusion criteria. After quality assessment and data extraction from the eligible studies, a meta-analysis was conducted using the STATA 12.0 software (Stata corporation, College Station, Texas, USA). Results Thirteen studies met all inclusion criteria and were included in the analysis. In total, these studies included 13,751 patients. Of the patients, 8444 of them underwent neurosurgical clipping, and 5307 underwent endovascular coiling. The overall result of a pooled estimate revealed there was no statistically significant risk of shunt dependency difference between the clipping and coiling groups (11.4% vs. 12.0%, respectively; relative risk [RR], 0.92; 95% confidence interval [CI], 0.84–1.01). Six prospective studies (n = 1373) reported shunt-dependent hydrocephalus revealed no significant difference between clipping and coiling (23.3% vs. 20.1%, respectively; RR, 1.12; 95% CI, 0.91–1.38). Seven retrospective studies (n = 12,378) reported shunt-dependent hydrocephalus found statistical significance between the surgical and endovascular treatment groups (10.0% vs. 11.1%, respectively; RR, 0.88; 95% CI, 0.79–0.98). Conclusions Microsurgical clipping and endovascular coiling of ruptured cerebral aneurysms are associated with similar incidences of ventricular shunt placement for hydrocephalus. The risk of shunt-dependent hydrocephalus is not higher after coiling than after clipping of ruptured intracranial aneurysms.

Background Interleukin-33 (IL-33) is an inflammatory biomarker. We elucidated the relationship between serum IL-33 concentrations, severity and prognosis in aneurysmal subarachnoid hemorrhage (aSAH). Methods We prospectively recruited 175 controls and 175 aSAH patients. Serum IL-33 concentrations were gauged using an enzyme-linked immunosorbent assay. Clinical and radiological severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale respectively. Poor outcome was defined as Glasgow Outcome Scale score of 1–3. Results Serum IL-33 concentrations were significantly higher in patients than in controls. IL-33 concentrations were significantly increased with increasing WFNS scores, modified Fisher scores and serum C-reactive protein concentrations. Serum IL-33 emerged as an independent predictor for 6-month mortality and poor outcome. Under receiver operating characteristic curve, the prognostic predictive ability of serum IL-33 was equivalent to those of WFNS scores and modified Fisher scores. Moreover, serum IL-33 significantly improved the prognostic predictive performance of WFNS scores and modified Fisher scores. Conclusions High serum IL-33 concentrations have close relation to the inflammation, severity and poor outcome in aSAH, indicating IL-33 might have the potential to be an inflammatory biomarker for assessing severity and reflecting prognosis of aSAH.

A large cranial defect combined with hydrocephalus is a frequent sequela of decompressive craniectomy (DC) performed to treat malignant intracranial hypertension. Currently, many neurosurgeons perform simultaneous cranioplasty and shunt implantation on such patients, but the safety of this combined procedure remains controversial.We retrospectively evaluated 58 patients treated via cranioplasty and shunt implantation after DC. Twenty patients underwent simultaneous procedures (simultaneous operation group) and 38 underwent staged procedures (staged operation group). We collected and analysed demographic data, information on disease histories, and clinical findings.The overall complication rate was 19%. The two groups did not significantly differ regarding the all-complication (30% vs. 13%), bleeding complication (0% vs. 5%), or treatment failure (15% vs. 3%) rates. However, the rate of surgical site infection/incision healing problems (25% vs. 3%) and the re-operation rate (20% vs. 3%) were significantly higher in the simultaneous operation group.Patients undergoing simultaneous cranioplasty/shunt implantation may be at a higher risk of infectious complications than those undergoing staged operations.

OBJECTIVEErythropoietin (EPO) exerts a neuroprotective effect in animal models of traumatic brain injury (TBI). However, its effectiveness in human patients with TBI is unclear. In this study, the authors conducted the first meta-analysis to assess the effectiveness and safety of EPO in patients with TBI.METHODSIn December 2015, a systematic search was performed of PubMed, Web of Science, MEDLINE, Embase, the Cochrane Library databases, and Google Scholar. Only English-language publications of randomized controlled trials (RCTs) using EPO in patients with TBI were selected for analysis. The assessed outcomes included mortality, favorable neurological outcome, hospital stay, and associated adverse effects. Continuous variables were presented as mean difference (MD) with a 95% confidence interval (CI). Dichotomous variables were presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Statistical heterogeneity was examined using both I2 and chi-square tests.RESULTSOf the 346 studies identified in the search, 5 RCTs involving 915 patients met the inclusion criteria. The overall results demonstrated that EPO significantly reduced mortality (RR 0.69, 95% CI 0.49–0.96, p = 0.03) and shortened the hospitalization time (MD −7.59, 95% CI −9.71 to −5.46, p < 0.0001) for patients with TBI. Pooled results of favorable outcome (RR 1.00, 95% CI 0.88–1.15, p = 0.97) and deep vein thrombosis (DVT; RD 0.00, 95% CI −0.05 to 0.05, p = 1.00) did not show a significant difference.CONCLUSIONSThe authors suggested that EPO is beneficial for patients with TBI in terms of reducing mortality and shortening hospitalization time without increasing the risk of DVT. However, its effect on improving favorable neurological outcomes did not reach statistical significance. Therefore, more well-designed RCTs are necessary to ascertain the optimum dosage and time window of EPO treatment for patients with TBI.

A large cranial defect following decompressive craniectomy (DC) is a common sequela in patients with severe traumatic brain injury (TBI). Such a defect can cause severe disturbance of cerebral blood flow (CBF) regulation. This study investigated the impact of cranioplasty on CBF in these patients.Patients who underwent DC and secondary cranioplasty were prospectively studied for a severe TBI. CT perfusion was used to measure CBF before and after cranioplasty. The basal ganglia, parietal lobe and occipital lobe on the decompressed side were chosen as zones of interest for CBF evaluation.Nine patients representing nine cranioplasty procedures were included in the study. Before cranioplasty, CBF on the decompressed side was lower than that on the contralateral side. During the early stage (10 days) after cranioplasty, CBF on the decompressed side was increased and this increase was significant in the parietal and occipital lobe. CBF was also increased on the contralateral side. In addition, the difference in CBF between the contralateral side and the decompressed side was reduced after cranioplasty. Further, the CT perfusion showed that the CBFs decreased again 3 months post-cranioplasty among four cases, but was still higher than those before cranioplasty.This study indicates that cranioplasty may increase CBF and benefit the recovery in patients with DC for TBI.

Background: The Marshall computed tomography (CT) system for classification of traumatic brain injury (TBI) includes the most important independent prognostic variables except for traumatic subarachnoid hemorrhage (tSAH). Objectives: To evaluate the prognostic effect of tSAH on different injury types based on the Marshall CT system. Methods: We performed a retrospective study. All patients with severe closed head injury admitted from February 2011 to July 2012 were included. Their scans were classified into two groups: localized injury and diffuse injury using the Marshall classification. Outcomes were compared between patients with tSAH and those without tSAH among the two groups. Results: Ninety-six patients were included in this study. Seventy-two (75%) were found to have tSAH, and outcomes significantly negatively correlated with tSAH in both localized injury and diffused injury groups. Conclusions: tSAH had an important effect on the patients’ outcome. Although the Marshall classification includes important independent prognostic variables, tSAH should also be added.

A 40-year-old man suffered severe brain injury and received left side subdural hematoma evacuation with decompressive craniectomy. Intraoperative brain swelling had occurred during the surgery. Postoperative computed tomography (CT) scan was done immediately and showed a contralateral epidural hematoma resulting in herniation. Secondary hematoma evacuation was performed and found a linear fracture near a bleeding meningeal artery. 2 days later CT scan showed cerebral infarction mainly in right posterior cerebral artery distribution. Early diagnosis by postoperative CT scan or other potential ways such as intraoperative sonography is important to prompt treatments and interrupt the pathophysiological chain of the serial attacks.

Background: Decompressing craniectomy (DC) is an important method for the management of severe traumatic brain injury (TBI). Objective: To analyze the effect of prophylactic DC within 24 hours after head trauma TBI. Methods: Seventy-two patients undergoing prophylactic DC for severe TBI were included in this retrospective study. Both of the early and late outcomes were studied and the prognostic factors were analyzed. Results: In this series, cumulative death in the first 30 days after DC was 26%, and 28 (53%) of 53 survivors in the first month had a good outcomes. The factors including Glasgow Coma Score (GCS) score at admission, whether the patient had an abnormal pupil response and whether the midline shift was greater than 5 mm were most important prognostic factors for the prediction of death in the first 30 days and the final outcome at 6 months after DC. Conclusion: Prophylactic DC plays an important role in the management of highly elevated ICP, especially when other methods of reduction of ICP are unavailable.

Contralateral haematoma is an infrequent but severe complication of decompressive craniectomy for head trauma.A retrospective study was performed of patients developing this complication after decompressive craniectomy for head trauma in the institute. Demographics, mechanism of trauma, time interval between trauma and first operation, time interval between first operation and onset of contralateral haematoma and patients' outcomes were recorded for further analysis.Fifteen patients developed this complication in the study; most had epidural haematomas, which appeared within the first 12 hours after decompressive craniectomy in 13 patients, including three haematomas that developed during surgical decompression. Contralateral cranial fracture is a major risk factor for this condition. Only one patient recovered to mild disability. All remaining patients had poor outcomes, with Glasgow coma scale scores ≤3, except for one patient who was lost to follow-up. A literature review of similar studies including 36 patients revealed similar characteristics.Contralateral haematoma secondary to surgical decompression in head trauma can lead to a poor outcome. The prompt detection and removal of the haematoma are keys to management and routine recurrent computed tomography is recommended after the first operation.

Thioredoxin (TRX), a potent anti-oxidant, is released during inflammation and oxidative stress. The purpose of this study was to establish the relationship between serum TRX concentrations and trauma severity and outcome in severe traumatic brain injury (STBI).We determined serum TRX concentrations in 112 patients and 112 controls. Multivariate analyses were performed to analyze the predictive factors of 1-week mortality, 6-month mortality and 6-month unfavorable outcome. The predictive values were investigated under receiver operating characteristic curves.Serum TRX concentrations were markedly higher in patients than in controls (19.1±7.8ng/ml vs. 8.0±2.3ng/ml, P0.001). There was a significant negative association between serum TRX concentrations and Glasgow coma scale (GCS) scores (r=-0.543, P0.001). Increased TRX was identified as an independent prognostic marker of 1-week mortality [Odds ratio (OR), 1.220; 95% confidence interval (CI), 1.101-1.367; P0.001], 6-month mortality (OR, 1.201; 95% CI, 1.097-1.324; P0.001) and 6-month unfavorable outcome (OR, 1.189; 95% CI, 1.090-1.311; P0.001). TRX concentrations improved area under curve of GCS scores for 6-month unfavorable outcome, but not for 1-week mortality and 6-month mortality.Increased serum TRX concentration, associated highly with trauma severity and poor outcome, might be a novel prognostic marker in patients with STBI.

The objective of the study was to evaluate the effectiveness of the supraorbital "keyhole" approach with endoscope assistance in surgical treatment of benign tumors around the sellar region. Thirty-five patients, including 19 pituitary tumors, 11 craniopharyngiomas and five tuberculum sellae meningiomas, were enrolled in this study. The tumors were resected through an endoscope-assisted supraorbital keyhole approach via a small skin incision within the eyebrow. Complete removal of the sellar region tumors was achieved in all 35 cases by endoscope-assisted supraorbital keyhole approach. Mean length of hospital stay after surgery was 10.2 days (range 5 - 17). There was no patient with evidence of residual or recurrent tumor during the follow-up period. There was no infection, bleeding, further vision impairment, oculomotor nerve injury or other cranial nerve injury symptom owing to surgery. Though some patients suffered from insipidus, hyperprolactinemia, subcutaneous edema or other postoperative complications, they eventually recovered with or without drug administration. The supraorbital "keyhole" approach with endoscopic assistance in the surgical treatment of benign tumors around the sellar region is an ideal pattern.

Decompressive craniectomy is an important method for managing traumatic brain injury (TBI). At present, controversies about this procedure exist, especially about the optimum operative time for patients with TBI.A prospective study was performed at the First Affiliated Hospital, College of Medicine, Zhejiang University. From January 2008 to December 2009, 25 patients who underwent early decompressive craniectomy were included in the study group, and 19 patients who underwent "late" decompressive craniectomy as a second-tier therapy for intracranial hypertension were included as a comparison group.The 30-day mortality after the operation was 16% in the study group. The overall mortality rate was 20% at the 6-month follow-up. A total of 52% of the patients (13 patients) had good outcomes, and 7 patients remained in a severely disabled or vegetative state. In the comparison group, 4 patients died, and 12 had good outcomes at the 6-month follow-up. The remaining 3 patients had poor outcomes. The study group was well matched with the comparison group. However, the outcomes in the study group were not better than those in the comparison group, as evaluated by the 6-month GOS score.Early decompressive craniectomy as a first-tier therapy for intracranial hypertension did not improve patient outcome when compared with "late" decompressive craniectomy for managing TBI.

Post-traumatic hydrocephalus (PTH) is a frequent complication secondary to traumatic brain injury (TBI) and controversy remains over whether to perform a shunt placement for patients with normal pressure hydrocephalus when the patient is too injured to display symptoms or has atypical symptoms.A hospital-based retrospective study was performed in patients who developed normal pressure hydrocephalus, without atypical symptoms, from January 2004 to June 2007. Information regarding patients' demographics, TBI, hydrocephalus and outcome was collected.A total of 31 patients were involved in this study. At the 12-month follow-up, 20 patients (64.5%) showed clear improvement. Among the 10 patients who developed PTH after decompressive craniectomy, cranioplasty was performed after shunt implantation and clinical improvement was observed in nine patients. Additionally, in this series, the patients' age and the severity of hydrocephalus, assessed by CT imaging before shunt placement, significantly correlated with improvement.Although the effect was not definitively established, many patients in the sub-group of PTH patients described here would benefit from shunt placement, especially when they simultaneously have large cranial defects after surgical decompression and underwent cranioplasties after shunt placement. Additionally, younger patients and those with less severe hydrocephalus before shunt placement may expect a better outcome after shunt placement.

Ethnopharmacological relevance ShuXueTong injection is a traditional Chinese drug designed to treat the patients of “blood stasis and stagnation (yu xue yu zhi)”, including subacute brain trauma. However, the mechanism of the therapeutic effect of ShuXueTong on traumatic brain injury is unknown yet. Aim of the study We hypothesized that ShuXueTong may promote the brain wound healing by facilitating angiogenesis. Thus this study was designed to explore this hypothesis. Materials and methods By means of microvessel count, Western blotting, immunocytochemistry, methyl thiazolyl tetrazolium assay and etc., the effect of ShuXueTong on the angiogenesis of brain wound was studied and then its influence on the VEGF/VEGFR-2 pathway were explored. Results ShuXueTong facilitates angiogenesis in the brain wound and improves the neurological function of the traumatized rats. VEGF expression in the lesion was elevated due to ShuXueTong induction. The in vitro experiment revealed VEGFR-2 and SRF expression in the endothelial cells were enhanced when exposed to ShuXueTong for merely 1 d. Moreover, ShuXueTong promoted the endothelial cell proliferation via the VEGF/VEGFR-2 pathway. Conclusions The mechanism of the therapeutic effect of ShuXueTong on traumatic brain injury lies at least partly in the enhanced angiogenesis in the lesion.

To study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI).In this study, totally 42 rabbits in 7 groups were studied. Six of the animals were identified as a control group, and the remaining 36 animals were equally divided into 6 TBI groups. TBI models were produced by the modified method of Feeney. After the impact, ICP of each subject was recorded continuously by an ICP monitor until the animal was sacrificed at scheduled time. The apoptotic brain cells were detected by an terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. Cerebral water content (CWC) was measured with a drying method and calculated according to the Elliott formula. Then, an analysis was conducted to determine the correlation between the count of apoptotic cells and the clinical pathological changes of the brain.Apoptotic cell count began to increase 2 h after the impact, and reached its maximum about 3 days after the impact. The peak value of CWC and ICP appeared 1 day and 3 days after the impact, respectively. Apoptotic cell count had a positive correlation with CWC and ICP.In TBI, occurrence of brain edema and ICP increase might lead to apoptosis of brain cells. Any therapy which can relieve brain edema and/or decrease ICP would be able to reduce neuron apoptosis, thereby to attenuate the secondary brain damage.