The role of SPI1/VSIG4/THBS1 on glioblastoma progression through modulation of the PI3K/AKT pathway.

INTRODUCTION: Glioblastoma multiforme (GBM) poses a significant challenge in terms of treatment due to its high malignancy, necessitating the identification of additional molecular targets. VSIG4, an oncogenic gene participates in tumor growth and migration in various cancer types. Nevertheless, the precise process through which VSIG4 facilitates the malignant progression of glioma remains to be elucidated. OBJECTIVES: This research aims to explore the function and molecular mechanism involving VSIG4 in the malignant progression of glioma. METHODS: The amount of VSIG4 was measured using qPCR, western blotting, and immunohistochemistry. Lentivirus infections were applied for upregulating or downregulating molecules within glioma cells. The incorporation of 5-ethynyl-20-deoxyuridine, Transwell, cell counting kit-8, and clone formation experiments, were applied to assess the biological functions of molecules on glioma cells. Dual luciferase reporter gene, RNA immunoprecipitation, and chromatin immunoprecipitation assays were used to explore the functional relationship among relevant molecules. RESULTS: The upregulation of VSIG4 was observed in GBM tissues, indicating an adverse prognosis. Silencing VSIG4 in glioma cells resulted in a decrease in cell viability, invasion, proliferation, and tumorigenesis, an increase in cell apoptosis, and a stagnation in the cell cycle progression at the G0/G1 phase. Mechanistically, SPI1-mediated upregulation of VSIG4 expression led to binding between VSIG4 and THBS1 protein, ultimately facilitating the malignant progression of glioma cells through the activation of the PI3K/AKT pathway. The inhibited proliferative and invasive capabilities of glioma cells were reversed by overexpressing THBS1 following the knockdown of VSIG4. CONCLUSION: Our findings provide evidence for the role of VSIG4 as an oncogene and reveal the previously unidentified contribution of the SPI1/VSIG4/THBS1 axis in the malignant progression of glioma. This signaling cascade enhances tumor growth and invasion by modulating the PI3K/AKT pathway. VSIG4 as a potential biomarker may be a viable strategy in the development of tailored molecular therapies for GBM.

Transcriptomics and metabolomics reveal hypothalamic metabolic characteristics and key genes after subarachnoid hemorrhage in rats.

Subarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.

Scoring model to predict postoperative neurological deterioration in spinal schwannoma.

Background: Spinal schwannomas (SSs) are benign tumors affecting the nerve sheath, accounting for 25% of spinal nerve root tumors. Surgery represents the mainstay of treatment for SS patients. Following surgery, approximately 30% of patients experienced developed new or worsening neurological deterioration, which probably represented an inevitable complication of nerve sheath tumor surgery. The objective of this study was to identify the rates of new or worsening neurological deterioration in our center and accurately predict the neurological outcomes of patients with SS by developing a new scoring model. Methods: A total of 203 patients were retrospectively enrolled at our center. Risk factors associated with postoperative neurological deterioration were identified by multivariate logistic regression analysis. ß-coefficients for independent risk factors were used to define a numerical score to generate a scoring model. The validation cohort at our center was used to verify the accuracy and reliability of the scoring model. Receiver operating characteristic (ROC) curve analysis was used to evaluate the performance of the scoring model. Results: In this study, five measured variables were selected for the scoring model: duration of preoperative symptoms (1 point), radiating pain (2 points), tumor size (2 points), tumor site (1 point), and dumbbell tumor (1 point). The scoring model divided the spinal schwannoma patients into three categories: low risk (0-2 points), intermediate risk (3-5 points), and high risk (6-7 points), with predicted risks of neurological deterioration of 8.7%, 36%, and 87.5%, respectively. And the validation cohort confirmed the model with the predicted risks of 8.6%, 46.4%, and 66.6%, respectively. Conclusion: The new scoring model might intuitively and individually predict the risk of neurological deterioration and may aid individualized treatment decision-making for SS patients.

Analysis of the efficacy and related factors of ventriculoperitoneal shunt for AIDS with cryptococcal meningitis.

Background: Cryptococcus neoformans is an opportunistic pathogen, which is more common in patients with AIDS. Increased intracranial pressure (ICP) is an important complication of cryptococcal meningitis (CM) and affects the therapeutic effect of CM. Objective: To evaluate the effect and treatment for the management of ventriculoperitoneal shunt (VPS) in the treatment of AIDS complicated with CM and to analyze the factors associated with VPS and the indices affecting the outcome of CM patients. Methods: A retrospective case study was conducted on patients with CM treated in the First Affiliated Hospital of Zhejiang University School of Medicine from 2011 to 2019. The Chi-square test was used for categorical variables and the Student's t-test was used for continuous variables. Multivariable analysis of baseline factors related to VPS placement was performed with stepwise logistic regression analysis, factors associated with the outcome of these patients were studied by Cox regression analysis, and Kaplan-Meier survival curves were constructed to assess the outcome of patients. Results: There were 96 patients with AIDS complicated with CM. VPS had a great effect on the patients, especially those with ICP > 350 mmH2O. The outcome, including the mortality rate and modified Rankin scale (MRS) score of these patients, significantly improved after the placement of VPS. The karnofsky performance status (KPS) scores of patients whose ICP > 350 mmH2O improved from 39.3 ± 21.3 at baseline to 88.7 ± 26.9 at 3 months after VPS, better than those without VPS. Multivariable analysis showed that visual impairment (OR, 0.026; 95% CI, 0.001, 0.567; P = 0.021) and ICP > 350 mmH2O (OR, 0.026; 95% CI, 0.002, 0.293; P = 0.003) were related elements with the placement of shunt, and KPS score (HR, 0.968; 95% CI, 0.943, 0.993; P = 0.013) and ICP > 350 mmH2O (HR, 2.801; 95% CI, 1.035, 7.580; P = 0.043) were indices of the outcome of AIDS patients with CM. For patients with ICP > 350 mmHg, Kaplan-Meier analysis showed that the 3-year outcome of patients with VPS was better than that of patients without VPS (P = 0.0067). Conclusion: VPS was associated with better 3-year survival rates, and postshunt placement complications like infections were rare. The identification of factors related to VPS in the initial diagnosis of CM can contribute to more active management and improve the outcome.

PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia.

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.

Inhibition of miR-19a-3p decreases cerebral ischemia/reperfusion injury by targeting IGFBP3 in vivo and in vitro.

BACKGROUND: Inflammation and apoptosis are considered to be two main factors affecting ischemic brain injury and the subsequent reperfusion damage. MiR-19a-3p has been reported to be a possible novel biomarker in ischemic stroke. However, the function and molecular mechanisms of miR-19a-3p remain unclear in cerebral ischemia/reperfusion (I/R) injury. METHODS: The I/R injury model was established in vivo by middle cerebral artery occlusion/reperfusion (MCAO/R) in rats and in vitro by oxygen-glucose deprivation and reperfusion (OGD/R) induced SH-SY5Y cells. The expression of miR-19a-3p was determined by reverse transcription quantitative PCR. The infarction volumes, Neurological deficit scores, apoptosis, cell viability, pro-inflammatory cytokines and apoptosis were evaluated using Longa score, Bederson score, TTC, TUNEL staining, CCK-8, ELISA, flow cytometry assays. Luciferase reporter assay was utilized to validate the target gene of miR-19a-3p. RESULTS: We first found miR-19a-3p was significantly up-regulated in rat I/R brain tissues and OGD/R induced SH-SY5Y cells. Using the in vivo and in vitro I/R injury model, we further demonstrated that miR-19a-3p inhibitor exerted protective role against injury to cerebral I/R, which was reflected by reduced infarct volume, improved neurological outcomes, increased cell viability, inhibited inflammation and apoptosis. Mechanistically, miR-19a-3p binds to 3'UTR region of IGFBP3 mRNA. Inhibition of miR-19a-3p caused the increased expression of IGFBP3 in OGD/R induced SH-SY5Y cells. Furthermore, we showed that IGFBP3 overexpression imitated, while knockdown reversed the protective effects of miR-19a-3p inhibitor against OGD/R-induced injury. CONCLUSIONS: In summary, our findings showed miR-19a-3p regulated I/R-induced inflammation and apoptosis through targeting IGFBP3, which might provide a potential therapeutic target for cerebral I/R injury.

Comparing the Risk of Shunt-Dependent Hydrocephalus in Patients with Ruptured Intracranial Aneurysms Treated by Endovascular Coiling or Surgical Clipping: An Updated Meta-Analysis.

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.

Increased serum interleukin-33 concentrations predict worse prognosis of aneurysmal subarachnoid hemorrhage.

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.

The safety of simultaneous cranioplasty and shunt implantation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Patients undergoing simultaneous cranioplasty/shunt implantation may be at a higher risk of infectious complications than those undergoing staged operations.

Therapeutic effect of erythropoietin in patients with traumatic brain injury: a meta-analysis of randomized controlled trials.

OBJECTIVE Erythropoietin (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. METHODS In 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. RESULTS Of 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. CONCLUSIONS The 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.

Serial Attacks: Contralateral Hematoma Secondary to Decompressive Craniectomy for Traumatic Brain Injury Led to Posttraumatic Cerebral Infarction.

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.

Change of serum levels of thioredoxin in patients with severe traumatic brain injury.

BACKGROUND: 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). METHODS: 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. RESULTS: Serum TRX concentrations were markedly higher in patients than in controls (19.1±7.8ng/ml vs. 8.0±2.3ng/ml, P<0.001). There was a significant negative association between serum TRX concentrations and Glasgow coma scale (GCS) scores (r=-0.543, P<0.001). 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; P<0.001], 6-month mortality (OR, 1.201; 95% CI, 1.097-1.324; P<0.001) and 6-month unfavorable outcome (OR, 1.189; 95% CI, 1.090-1.311; P<0.001). TRX concentrations improved area under curve of GCS scores for 6-month unfavorable outcome, but not for 1-week mortality and 6-month mortality. CONCLUSIONS: Increased serum TRX concentration, associated highly with trauma severity and poor outcome, might be a novel prognostic marker in patients with STBI.

The impact of cranioplasty on cerebral blood perfusion in patients treated with decompressive craniectomy for severe traumatic brain injury.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: This study indicates that cranioplasty may increase CBF and benefit the recovery in patients with DC for TBI.

Contralateral haematoma secondary to decompressive craniectomy performed for severe head trauma: a descriptive study of 15 cases.

BACKGROUND: Contralateral haematoma is an infrequent but severe complication of decompressive craniectomy for head trauma. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Traditional Chinese drug ShuXueTong facilitates angiogenesis during wound healing following traumatic brain injury.

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 1d. 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.

Endoscope-assisted supraorbital keyhole approach for the resection of benign tumors of the sellar region.

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.

Correlation of cell apoptosis with brain edema and elevated intracranial pressure in traumatic brain injury.

OBJECTIVE: To study the correlation between brain edema, elevated intracranial pressure (ICP) and cell apoptosis in traumatic brain injury (TBI). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.