Genetically predicted N-Acetyl-L-Alanine mediates the association between CD3 on activated and secreting Tregs and Guillain-Barre syndrome.

Objective: This study sought to explore the potential causal relationships among immune cell traits, Guillain-Barre syndrome (GBS) and metabolites. Methods: Employing a two-sample Mendelian randomization (MR) approach, the study investigated the causal associations between 731 immune cell traits, 1400 metabolite levels and GBS leveraging summary-level data from a genome-wide association study (GWAS). To ensure the reliability of our findings, we further assessed horizontal pleiotropy and heterogeneity and evaluated the stability of MR results using the Leave-one-out method. Results: This study revealed a causal relationship between CD3 on activated & secreting Tregs and GBS. Higher CD3 on activated and secreting Regulatory Tregs increased the risk of GBS (primary MR analysis odds ratio (OR) 1.31/SD increase, 95% confidence interval (CI) 1.08-1.58, p = 0.005). There was no reverse causality for GBS on CD3 on activated & secreting Tregs (p = 0.36). Plasma metabolite N-Acetyl-L-Alanine (ALA) was significantly positively correlated with GBS by using the IVW method (OR = 2.04, 95% CI, 1.26-3.30; p = 0.00038). CD3 on activated & secreting Tregs was found to be positively associated with ALA risk (IVW method, OR, 1.04; [95% CI, 1.01-1.07], p = 0.0078). Mediation MR analysis indicated the mediated proportion of CD3 on activated & secreting Tregs mediated by ALA was 10% (95%CI 2.63%, 17.4%). Conclusion: In conclusion, our study identified a causal relationship between the level of CD3 on activated & secreting Tregs and GBS by genetic means, with a considerable proportion of the effect mediated by ALA. In clinical practice, thus providing guidance for future clinical research.

Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque.

Background and purpose: Cardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients. Methods: A cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors. Results: Patients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94-7.46, p < 0.001), dyslipidemia (OR 2.36, 95% CI 1.22-4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50-5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12-4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19-0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10-9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (< 6.20 mmol/L), the patients in the third tertile (> 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85-16.66, p = 0.002). Conclusion: The findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization.

Thrombectomy Alone or Alongside Intravenous Thrombolysis in Managing Acute Ischemic Stroke Caused by Basilar Artery Occlusion: A Multicenter Observational Study.

BACKGROUND AND PURPOSE: It remains unclear whether the combination of endovascular treatment (EVT) with intravenous thrombolysis (IVT) results in a more favorable functional outcome than EVT alone in managing cases of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO). Thus, this study aimed to compare the outcomes of two approaches-direct EVT (DEVT) and bridging therapy (IVT plus EVT)-in acute BAO patients presenting within 4.5 hours of stroke onset. MATERIALS AND METHODS: This multicenter retrospective cohort study included 153 acute BAO patients presenting within 4.5 hours of stroke onset. Of these patients, 65 (42.5%) and 88 (57.5%) underwent DEVT and bridging therapy, respectively. The primary outcome was defined as good functional outcome (modified Rankin Scale, 0-3) at 90 days. Additionally, pre-operative clinical features, thrombectomy attempts, successful reperfusion rates, incidences of symptomatic intracranial hemorrhage (sICH), and mortality were compared between the two groups. RESULTS: At 90 days, the rate of good functional outcome was comparable between the DEVT (44.6%) and bridging-therapy (39.8%) groups (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 0.55-2.31; p = 0.753). The bridging-therapy group exhibited a lower percentage of patients requiring ≥ 3 attempts of stent retrieval (aOR, 0.39; 95% CI, 0.16-0.93; p = 0.034). Pre-operative clinical features, rate of successful reperfusion, sICH, and mortality were similar between the two groups. CONCLUSIONS: In patients with BAO-induced AIS, DEVT demonstrates a comparable functional outcome to bridging therapy within 4.5 hours of symptom onset, but IVT reduces the number of thrombectomy attempts. ABBREVIATIONS: AIS, acute ischemic stroke; LVO, large-vessel occlusion; EVT, endovascular treatment; IVT, intravenous thrombolysis; BAO, basilar artery occlusion; DEVT, direct endovascular treatment; sICH, symptomatic intracranial hemorrhage; RCT, randomized controlled trial; IRIS, Improving Reperfusion Strategies in Ischemic Stroke; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; mTICI, modified thrombolysis in cerebral infarction; SD, standard deviation; IQR, interquartile range; ICAS, intracranial atherosclerotic stenosis.

Comparative Effectiveness of Therapies in 2665 Elderly Patients with Ruptured Intracranial Aneurysms.

BACKGROUND: The optimal treatment strategy for elderly patients with ruptured intracranial aneurysms (IAs) remains controversial. We evaluated a national, multihospital database to compare the outcomes of aggressive treatment and medical management for those patients. METHODS: We performed a retrospective analysis of 2665 elderly patients with ruptured IAs admitted to 11 hospitals in China. Patients were divided into three age groups (60-69, 70-79, and 80 years or older). Multiple logistic regression was used to estimate the odds ratio for favorable and unfavorable outcomes. RESULTS: Patients between 60 and 69 years old undergoing endovascular treatment (EVT) had significantly decreased morbidity (13.7% versus 19.7% and 29.9%), compared to those who underwent clipping and medical management, similar mortality to patients who underwent clipping (3.6% versus 2.6%), and decreased mortality (3.6% versus 8.7%) to patients who underwent medical management. Coiled patients 70 to 79 years old had lower morbidity (21.3% versus 33.8%) and mortality (2.8% versus 11.3%) compared to patients who underwent medical management and similar mortality (21.3% versus 27.2%) and mortality (2.8% versus 4.8%) to patients who underwent clipping. Multivariate logistic regression analysis demonstrated that factors associated with discharge status were age, poor mFisher grade, poor WFNS grade, hypertension, diabetes, smoking, aneurysms 4 mm or larger, and middle cerebral artery aneurysms. CONCLUSIONS: Elderly patients treated with EVT had significantly less morbidity and mortality than those treated with clipping and medical management. A comprehensive assessment of the general state of elderly patients and IAs characteristic may help us to predict patients' prognosis.

Technical Risk Stratification Nomogram Model for 90-Day Mortality Prediction in Patients With Acute Basilar Artery Occlusion Undergoing Endovascular Thrombectomy: A Multicenter Cohort Study.

BACKGROUND: This study aimed to establish and validate a nomogram model for predicting 90-day mortality in patients with acute basilar artery occlusion receiving endovascular thrombectomy. METHODS AND RESULTS: A total of 242 patients with basilar artery occlusion undergoing endovascular thrombectomy were enrolled in our study, in which 172 patients from 3 stroke centers were assigned to the training cohort, and 70 patients from another center were assigned to the validation cohort. Univariate and multivariate logistic regression analyses were adopted to screen prognostic predictors, and those with significance were subjected to establish a nomogram model in the training cohort. The discriminative accuracy, calibration, and clinical usefulness of the nomogram model was verified in the internal and external cohorts. Six variables, including age, baseline National Institutes of Health Stroke Scale score, Posterior Circulation-Alberta Stroke Program Early CT (Computed Tomography) score, Basilar Artery on Computed Tomography Angiography score, recanalization failure, and symptomatic intracranial hemorrhage, were identified as independent predictors of 90-day mortality of patients with basilar artery occlusion and were subjected to develop a nomogram model. The nomogram model exhibited good discrimination, calibration, and clinical usefulness in both the internal and the external cohorts. Additionally, patients were divided into low-, moderate-, and high-risk groups based on the risk-stratified nomogram model. CONCLUSIONS: Our study proposed a novel nomogram model that could effectively predict 90-day mortality of patients with basilar artery occlusion after endovascular thrombectomy and stratify patients with high, moderate, or low risk, which has a potential to facilitate prognostic judgment and clinical management of stroke.

Corrigendum: Smaller baseline subcortical infarct volume predicts good outcomes in patients with a large core in early acute ischemic stroke after endovascular treatment.

[This corrects the article DOI: 10.3389/fnins.2023.1063478.].

Smaller baseline subcortical infarct volume predicts good outcomes in patients with a large core in early acute ischemic stroke after endovascular treatment.

Background: Patients with acute ischemic stroke (AIS) and a large core may benefit from endovascular treatment (EVT) in the early time window. Purpose: To examine the prognostic factors for good outcomes in patients with a large core (70-130 ml) after EVT. Materials and methods: We retrospectively reviewed 40 patients who met the criteria from October 2019 to April 2021. Based on the modified Rankin Score (mRS) at 90 days, the patients were divided into a good outcome group (mRS 0-2) and a poor outcome group (mRS 3-6). Baseline and procedural characteristics were collected for unilateral and multivariate regression analyses to explore the factors that influence good outcomes. In particular, the infarct territories were quantified as subcortical infarct volume (SIV) and cortical infarct volume (CIV). Results: Of the 40 patients included, good outcomes were observed in 11 (27.5%) patients. Younger age, smaller SIV and larger mismatch volume were noted in the good outcome group than in the poor outcome group (all P < 0.05). Multivariate logistic regression analysis showed that only a smaller SIV [odds ratio (OR) 0.801; 95% CI 0.644-0.996; P = 0.046] was an independent predictor for good outcomes. The receiver operating characteristic curve indicated a moderate value of SIV for predicting good outcomes, with an area under the receiver operating characteristic curve of 0.735 (95% CI 0.572-0.862; P = 0.007). Conclusion: Subcortical infarct volume was a potential useful predictor of good outcomes in patients with a large core after EVT in the early time window.

Direct carotid artery puncture for acute ischemic stroke: Local experience and systematic review.

BACKGROUND: To establish surgical access during endovascular treatment of ischemic stroke, femoral artery puncture is most commonly performed followed by a small number of radial artery access procedures. However, there are few reports of carotid artery puncture. METHODS: We report the case of an 87-year-old woman who was admitted to hospital with hemiplegia of the left limb and loss of consciousness for 40 min, accompanied by urinary incontinence. After complicated transfemoral and transradial attempts, the patient underwent emergency direct carotid artery puncture (DCAP) for the treatment of acute ischemic stroke. We reviewed the literature on this topic over a 7-year period (September 2014 to April 2022), including 202 patients with acute ischemic stroke who underwent emergency DCAP and endovascular surgery. RESULTS: The average age of these patients was 80.5 years. The left DCAP accounted for 52.5% (106/202) of the cases. Local anesthesia was utilized in 33.9% (64/189) of the cases. Angio-Seal was utilized for closure in 53.7% (79/147) of the patients. About half (105/199) of the patients recovered or improved their limb function after DCAP. Postoperative complications were mainly neck hematoma and one of these patients died due to a fatal neck hematoma. CONCLUSION: We describe the detailed procedure of the rare case of an emergency DCAP performed at our institution. DCAP provides an alternative treatment method in cases where thrombus removal access cannot be established through traditional methods.

Cerebral Vasospasm-Left Heart Failure-Cerebral Infarction May Be a Potential Pathophysiological Mechanism of Malignant Cerebral Vasospasm.

ABSTRACT: Cerebral vasospasm (CV) and delayed cerebral ischemia are serious complications after ruptured aneurysm with high mortality and disability rate. However, there are few reports of cardiogenic CV, the mechanism is unclear, and the treatment recommended by the guidelines is not detailed. This article describes in detail a 47-year-old woman with intracranial aneurysm rupture and hemorrhage. After interventional operation, left heart failure worsened CV and cerebral infarction. This article summarizes the diagnosis and treatment process of patients in detail, summarizes the treatment strategies of cardiogenic CV, and elaborates the pathological mechanism of CV-left heart failure-CV and cerebral infarction. increase new understanding of the clinical diagnosis and treatment strategies of cardiogenic CV.

Mechanical Embolectomy for Superior Cerebellar Artery Embolism.

ABSTRACT: Acute embolism of the superior cerebellar artery is rarely reported. The treatment is mainly medication, decompressive craniectomy is performed when necessary, and mechanical thrombus removal is not recommended. This article describes the admission of a 69-year-old man with acute superior cerebellar artery embolization. Compared with the imaging data of the patient 2 weeks before the onset of the disease, cerebral angiography revealed that there was a mural thrombus covering the opening of the superior cerebellar artery. it is also a bold attempt for this patient to undergo mechanical thrombectomy. The patient finally recovered well from neurological symptoms. This case report details the causes of the rare mural thrombosis leading to superior cerebellar artery embolism, and also has a new understanding of arterial embolism in acute stroke.

Glioma stem cell-derived exosomal miR-944 reduces glioma growth and angiogenesis by inhibiting AKT/ERK signaling.

In this study, we investigated the regulatory role of exosomal microRNA-944 (miR-944) derived from glioma stem cells (GSCs) in glioma progression and angiogenesis. Bioinformatics analysis showed that miR-944 levels were significantly lower in high-grade gliomas (HGGs) than low-grade gliomas in the Chinese Glioma Genome Atlas and The Cancer Genome Atlas datasets. The overall survival rates were significantly shorter for glioma patients expressing low miR-944 levels than high miR-944 levels. GSC-derived exosomal miR-944 significantly decreased in vitro proliferation, migration, and tube formation by human umbilical vein endothelial cells (HUVECs). Targetscan and dual luciferase reporter assays demonstrated that miR-944 directly targets the 3'UTR of VEGFC. In vivo mouse studies demonstrated that injection of agomiR-944 directly into tumors 3 weeks after xenografting glioma cells significantly reduced tumor growth and angiogenesis. GSC-derived exosomal miR-944 significantly reduced VEGFC levels and suppressed activation of AKT/ERK signaling pathways in HUVECs and xenograft glioma cell tumors. These findings demonstrate that GSC-derived exosomal miR-944 inhibits glioma growth, progression, and angiogenesis by suppressing VEGFC expression and inhibiting the AKT/ERK signaling pathway.

Management of Elevated Blood Pressure After Stroke Thrombectomy for Anterior Circulation.

Thrombectomy is superior to intravenous thrombolysis for patients with large vessel occlusion in acute ischemic stroke, but nearly half of the patients still experience poor functional outcomes. Elevated blood pressure (BP) is widely observed in acute ischemic stroke, and BP may be one of the modifiable parameters that can potentially influence the outcomes; however, only observational studies exist to support current guidelines, and the recommended range for BP after thrombectomy is too wide to meet the clinical requirement. Randomized controlled trials are therefore needed to better understand the relationship between BP and outcomes after thrombectomy. In this review, we introduce the current management of BP after thrombectomy and several aspects of postthrombectomy BP management that should be resolved in future clinical trials.

Silencing of PRDM5 increases cell proliferation and inhibits cell apoptosis in glioma.

AIM: PR-domain-containing 5 (PRDM5), a family member of PR-domain-containing zinc finger genes, has been reported to participate in modulate cellular processes, including cell growth, differentiation and apoptosis. It has also been found to function as a putative tumor suppressor in different types of cancer. The present study is the first, to the best of our knowledge, to report on the clinical significance of the expression of PRDM5 in glioma cell line. MATERIALS AND METHODS: Western blot analyse the expression of PRDM5 in glioma tissues and cells. 80 tissues microarray samples from patients with glioma were examined using immunohistochemical analysis. Glioblastoma U251 cells were transfected with PRDM5-siRNA and control-siRNA. U251cell proliferation was measured by flow cytometric analysis and plate colony formation assay. Cell apoptosis were detected using flow cytometric analysis. RESULTS: The results of western blot analysis and immunohistochemistry showed that the expression of PRDM5 was decreased in fresh glioma tissues, compared with that in normal brain tissues. Kaplan-Meier postoperative survival curves demonstrated that the low expression of PRDM5 was associated with poor prognosis in patients with glioma. In addition, suppression of PRDM5 promoted cell proliferation via regulating cell cycle progression. Finally, knocking down PRDM5 using small interfering RNA decreased the apoptosis of glioma cells. CONCLUSION: Taken together, these findings suggested that PRDM5 may be a novel therapeutic target of glioma.

Cutaneous Metastases of the Glioma.

Low grade glioma (LGG) is a very common primary brain neoplasm with a very good prognosis and the median survival of patients is approximately 8 years. With the development of current treatments such as surgery resection, radiotherapy, and chemotherapy, the recurrence rate and the distant metastasis rate of LGGs are largely decreased. Extracranial metastases are seldom happened. However, the authors present a pathologically proven patient with scalp metastasis, which was metastasized from LGG occurring site to the surgical scar 8 months following initial craniotomy and chemotherapy. The histopathologic examination of the primary site and the recurrent under the scalp are exactly similar. This grade of glioma was increased along with cutaneous metastases. A discussion of a series of the extracranial metastases of the glioma, especially for the surgical considerations, is also provided advice for the cutaneous metastases of the glioma.

Suppression of the Smurf1 Expression Inhibits Tumor Progression in Gliomas.

Glioblastoma, one of the common malignant brain tumors, results in the highly death, but its underlying molecular mechanisms remain unclear. Smurf1, a member of Nedd4 family of HECT-type ligases, has been reported to contribute to tumorigenicity through several important biological pathways. Recently, it was also found to participate in modulate cellular processes, including morphogenesis, autophagy, growth, and cell migration. In this research, we reported the clinical guiding significance of the expression of Smurf1 in human glioma tissues and cell lines. Western blotting analysis discovered that the expression of Smurf1 was increased with WHO grade. Immunohistochemistry levels discovered that high expression of Smurf1 is closely consistent with poor prognosis of glioma. In addition, suppression of Smurf1 can reduce cell invasion and increase the E-cadherin expression, which is a marker of invasion. Our study firstly demonstrated that Smurf1 may promote glioma cell invasion and suppression of the Smurf1 may provide a novel treatment strategy for glioma.

Overexpression of interleukin-33 is associated with poor prognosis of patients with glioma.

Interleukin-33 (IL-33) has shown diagnostic and prognostic values in multiple human cancers. However, there is little knowledge on the role of IL-33 in human gliomas and its association with disease prognosis. This study aimed to evaluate the value of IL-33 in the prognosis of glioma patients. The expression of IL-33 was determined and compared in surgical specimens from 86 glioma patients and 16 normal brain tissues. The associations of IL-33 expression with the clinicopathological features and prognosis of glioma patients were assessed. qRT-PCR assay showed higher IL-33 mRNA expression in glioma tissues than in normal brain tissue ( p < 0.001), and significantly higher IL-33 mRNA expression was detected in both low- and high-grade glioma tissues relative to normal brain tissues ( p < 0.001). Western blotting revealed elevated IL-33 protein levels in glioma tissues compared to those in normal brain tissues, and immunohistochemical staining showed higher IL-33 protein expression in glioma tissues than in normal brain tissues. IL-33 expression correlated with the glioma grade ( p < 0.001) and Karnofsky performance status score ( p = 0.024), and the glioma patients with high IL-33 expression had a shorter progression-free survival ( p < 0.001) and overall survival ( p < 0.001) than those with low IL-33 expression. The univariate and multivariate analyses showed that IL-33 overexpression and the glioma grade were independent factors of a poor prognosis in glioma patients. Therefore, IL-33 may be a promising biomarker for the detection of gliomas, and IL-33 expression is useful for predicting the prognosis of the disease.

Increased serum concentrations of signal peptide-Cub-Egf domain-containing protein-1 in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1), a marker for coagulation, is correlated with prognosis of some critical illnesses. The current study was designed to investigate the potential prognostic value of serum SCUBE1 concentrations in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Serum SCUBE1 concentrations of 125 patients and 125 controls were determined. Multivariate analyses were performed to identify independent risk factors for 6-month mortality, overall survival and unfavorable outcome (Glasgow Outcome Scale score of 1-3). RESULTS: Serum SCUBE1 concentrations were significantly higher in patients than in controls (17.7±7. vs. 1.2±0.4ng/ml, P<0.001) and were associated highly with World Federation of Neurological Surgeons (WFNS) scores (t=5.109, P<0.001) and modified Fisher scores (t=4.329, P<0.001). SCUBE1 emerged as an independent predictor for 6-month clinical outcomes. It had similar area under receiver operating characteristic curve (AUC) to WFNS scores and modified Fisher scores. Moreover, it could markedly improve the AUC of WFNS scores and modified Fisher scores to predict 6-month unfavorable outcome. CONCLUSION: Enhanced SCUBE1 concentrations are correlated with increasing severity and poor outcomes of aSAH patients, indicating SCUBE1 might have the potential to identify aSAH patients at risk of poor prognosis.

Visual outcome after extended endoscopic endonasal transsphenoidal surgery for tuberculum sellae meningiomas.

BACKGROUND: The purpose of this study was to evaluate the visual outcome after extended endoscopic endonasal transsphenoidal surgery in patients with tuberculum sellae meningiomas (TSM). METHODS: A retrospective analysis was performed for 12 patients (4 men and 8 women) with TSMs who underwent extended endonasal transsphenoidal surgery with pure endoscopy between 2003 and 2008. Neuro-ophthalmic evaluation was performed preoperatively and postoperatively. Visual acuity, visual fields, and funduscopy results were documented during the preoperative and follow-up periods. RESULTS: There were three patients with bilateral optic foramen invasion and four patients with unilateral optic foramen invasion on radiologic findings preoperatively. Eleven patients had total tumor resection (Simpson grade I and II), and one patient had a subtotal tumor resection with a small asymptomatic tumor regrowth seen on magnetic resonance imaging at 14 months after surgery. Patients were observed for a mean follow-up time of 2.1 years (range 6 months-5 years), and the median was 28 months. Visual acuity improved in 92% of patients and was unchanged in 8% of patients. Eleven patients with visual field problems were better in various degrees at postoperative follow-up than before operation. No patients showed worsening of vision or visual field after surgery. CONCLUSIONS: In this small, selected series with a relatively short follow-up, the extended endoscopic endonasal transsphenoidal approach to TSMs was a feasible alternative to the transcranial approach with minimal manipulation of the optic nerve. Procedures in the subchiasmatic space can be performed effectively with excellent visualization of the blood network supply to the optic apparatus while preserving the optic nerve in most cases.

The expression of NF-E2-related factor 2 in the rat brain after traumatic brain injury.

BACKGROUND: Secondary brain damage plays a critical role in the outcome of patients with traumatic brain injury (TBI). The mechanisms underlying secondary brain damage are complex. A target that can interrupt multiple mechanisms underlying secondary brain damage may represent a promising new therapeutic approach for TBI. NF-E2-related factor 2 (Nrf2) is the key regulator in reducing oxidative stress, inflammatory damage, and the accumulation of toxic metabolites, which are all involved in secondary brain damage after TBI. Therefore, Nrf2 might represent a new direction for the treatment of TBI. However, the expression pattern of Nrf2 after TBI has not yet been studied. METHODS: This study involved the detection of Nrf2 mRNA levels by reverse-transcriptase polymerase chain reaction, and its nuclear protein levels by Western blot from 3 hour to 72 hour after TBI. Nrf2 distribution in the brain after TBI was also investigated by immunohistochemistry. RESULTS: After TBI, the nuclear Nrf2 protein level is significantly increased, whereas its mRNA level remains unchanged. Increased Nrf2 immunostaining was detected not only in the vulnerable regions but also in the brain barrier system. CONCLUSION: Nrf2 might play a protective role in the brain after TBI, possibly by reducing oxidative stress and brain edema.

Role of Nrf2 in protection against traumatic brain injury in mice.

Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. The present study investigated the role of Nrf2 in modulating traumatic brain injury (TBI)-induced secondary brain injury. Wild-type Nrf2 (+/+) and Nrf2 (-/-)-deficient mice were subjected to a moderately severe weight-drop impact head injury. The absence of Nrf2 function in mice resulted in exacerbated brain injury as shown by the increased severity of neurological deficit, apoptosis, and brain edema at 24h after TBI. This exacerbation of brain injury in Nrf2-deficient mice was associated with increased mRNA and protein expression of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6), and with decreased mRNA expression and enzymatic activity of antioxidant and detoxifying enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferase alpha-1 (GST-alpha1), compared with their wild-type counterparts after TBI. In combination, these results suggest that Nrf2 plays an important role in protecting TBI-induced secondary brain injury, possibly by regulating inflammatory cytokines and inducing antioxidant and detoxifying enzymes.