Peripheral Monocyte Percentage as a Potential Indicator of Prognosis in Patients with Chronic Subdural Hematoma Receiving Conservative Therapy.

BACKGROUND: Studies have confirmed active and abnormal inflammation in the hematoma cavity of chronic subdural hematoma (CSDH). However, a relationship between the peripheral blood status and the prognosis of CSDH patients has not been demonstrated. METHODS: We retrospectively analyzed 245 CSDH patients who received conservative therapy (67 under close follow-up observation, 103 treated with atorvastatin, and 75 treated with atorvastatin combined with dexamethasone) from 2014 to 2021 to evaluate the role of major inflammation-associated cells in the prognostic assessment of patients. Univariate and multivariate analyses were performed to assess the potential factors that could indicate the prognosis among the 103 patients who underwent observation only or atorvastatin therapy. Changes in peripheral blood inflammation-associated cells at different time points were compared between patients with good and poor outcomes. Furthermore, the changes in inflammatory cells in 75 patients who received atorvastatin combined with dexamethasone were analyzed. RESULTS: The monocyte percentage was the only independent influencing factor in subsequent follow-up assessments. Patients with good outcomes had obviously lower circulating monocyte percentages in their peripheral blood counts throughout the treatment period. The monocyte percentage was also significantly decreased in the patients who responded well to atorvastatin combined with dexamethasone. The peripheral monocyte percentage was significantly higher in patients who transitioned to surgery because of a poor response to pharmacotherapy. CONCLUSIONS: The peripheral monocyte percentage may be a convenient and effective indicator for predicting the outcome of CSDH for patients receiving conservative treatment. A higher percentage of monocytes could be a risk factor for a poor response.

Soft Coagulation Monopolar Suction for Rapid Resection of Supratentorial Brain Tumors: Feasibility of a New Technique and Outcomes.

OBJECTIVES: The aims of this study were to evaluate the feasibility of a new rapid tumor resection technique using soft coagulation monopolar suction (SCMS) and to strengthen neurosurgeons' understanding, use, and attention to this new electrosurgical technique. METHODS: The rapid surgical resection technique used herein comprised monopolar suction in soft coagulation mode applied by the ERBE VIO 300s workstation and conventional microsurgical suction. We applied this technique to supratentorial tumors in 12 patients (5 with glioblastomas, 4 with astrocytomas, 2 with metastases, and one with lymphoma) as the SCMS group. The conventional bipolar electrocautery and suction method was used for another 12 patients (non-SCMS group). The surgical results and perioperative complications were retrospectively evaluated. Radiographic and histologic analyses were performed to describe the degree of thermal damage. RESULTS: The mean estimated operative time and total blood loss were 3.63 ± 0.61 hours (P = 0.0048) and 308.33 ± 172.99 mL (P = 0.0482) in the SCMS group, respectively, and these values were significantly lower than those in the non-SCMS group (4.33 ± 0.49 hours and 466.67 ± 196.95 mL, respectively). No significant differences in perioperative complications, Karnofsky Performance Status scores, perioperative area edema volumes, perioperative ischemic areas, or mean residual tumors were observed between the groups. Histological examination revealed that SCMS produced uniform coagulation and completely obstructed most small vessel structures on the tumor surface. CONCLUSIONS: This new technique involving SCMS allows for a smooth surgical procedure and appears to be safe and feasible for the rapid resection of supratentorial brain tumors. Thus, neurosurgeons should consider using this technique in the future.

Risk Factor Analysis of the Conservative Treatment in Chronic Subdural Hematomas: A Substudy of the ATOCH Trial.

INTRODUCTION: The objective of the study was to analyze the risk factors for worsening of the disease progression in patients with chronic subdural hematomas (CSDH) during wait-and-observation treatment regimen and conservative treatment with atorvastatin. METHODS: A total of 196 patients with CSDH were recruited (98 in the atorvastatin group and 98 in the blank placebo group). Receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff for the hematoma volume by testing surgical and nonsurgical outcomes. Other measures, including univariate and multivariate analyses, were performed to identify the potential significant factors indicative of the outcome of therapeutic efficacy of conservative treatment through the characteristics of the baseline indicators at enrollment. RESULTS: Over a median treatment duration of 2 months, lower total cholesterol, higher hematoma volume, and more midline shift were independent risk factors for worse outcomes of atorvastatin treatment for CSDH, and only a higher hematoma volume was an independent risk factor for spontaneous absorption in the placebo group. ROC analysis of all of the data showed that the optimal threshold of hematoma volume was 68.5 ml (sensitivity 73.5%, specificity 74%) in response to the greatest chance of switching to surgery. CONCLUSIONS: Critical independent predictors of atorvastatin monotherapy treatment success included higher total cholesterol, lower hematoma volume, and less midline shift in atorvastatin monotherapy, and higher hematoma volume was the only independent risk factor in close follow-up observation patients without any pharmacotherapy. Initial hematoma volume more than 68.5 ml may help clinicians to determine individual risk assessments and to make optimal treatment decisions. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov . Identifier NCT02024373.

Atorvastatin combined with dexamethasone promote hematoma absorption in an optimized rat model of chronic subdural hematoma.

Previous studies found that atorvastatin and dexamethasone were effective in promoting the absorption of chronic subdural hematoma. In this study, we aimed to investigate the effect of pharmacotherapy in an optimized rat model of chronic subdural hematoma. Rat model of chronic subdural hematoma via a bEnd.3 cell and Matrigel mix was established and dynamic changes in different drug treatment groups were tested. The hematoma gradually increased, peaked on the fifth day (263.8±52.85 µl), and was completely absorbed in two weeks. Notably, Kruppelle-like factor 2 expression was significantly decreased with increasing hematoma volume, and then increased in the repair period. The expression of IL-10 was increased and peaked on 7 days, and then decreased at 14 days. The dynamic trends of IL-6, IL-8, MMP-9, and VEGF were also increased first and then decreased. Both monotherapy and the combined treatment by atorvastatin and dexamethasone could counteract the inflammatory activities, decrease hematoma permeability, and improve hematoma absorption, however, most prominent in combined group. The combined treatment could more effectively increase Kruppelle-like factor 2 and ZO-1 expression, attenuate the expression of NF-κb. Most importantly, the combined treatment enhanced the neural functional prognosis and reduced the mortality of chronic subdural hematoma rats. According to our results, the combined treatment could more effectively attenuate inflammatory. And it could also enhance angiogenic activities which could promote the stability of local function and structure of the hematoma cavity, reduce the hematoma volume and improve the outcomes of rats with chronic subdural hematoma than single treatments in the optimized chronic subdural hematoma model.

Expression and Tumor-Promoting Effect of Tyrosine Phosphatase Receptor Type N (PTPRN) in Human Glioma.

Tyrosine phosphatase receptor type N (PTPRN) plays an important role in the regulation of the secretion pathways of various neuroendocrine cells. Moreover, PTPRN was demonstrated to play a crucial role in the initiation and progression of the signalling cascade regulating cell function. In this study, fifty-seven glioma patients were enrolled for clinical and prognostic analyses. The cell phenotype was determined by cell proliferation and migration assays. RNA-seq, co-IP and mass spectrometry were used to study the molecular mechanism of the effects of PTPRN on cell proliferation and metastasis. The result showed that High expression of PTPRN indicated a poor prognosis of high-grade glioma. PTPRN downregulation reduced the proliferation and migration of glioma cells, and PTPRN overexpression induced the proliferation and migration of glioma cells. PTPRN knockdown decreased tumor growth in a mouse xenograft model. Effect of PTPRN knockdown on the transcriptome was studied in U87 glioma cells. PTPRN activated the PI3K/AKT pathway by interacting with HSP90AA1. In conclusion, PTPRN is an important proliferation- and metastasis-promoting factor. Reducing the expression of PTPRN in glioma cells can be used as a potential therapeutic strategy.

A novel rat model of chronic subdural hematoma: Induction of inflammation and angiogenesis in the subdural space mimicking human-like features of progressively expanding hematoma.

Pathophysiological mechanisms of chronic subdural hematoma (CSDH) involve localized inflammation, angiogenesis, and dysregulated coagulation and fibrinolysis. The scarcity of reproducible and clinically relevant animal models of CSDH hinders further understanding the underlying pathophysiology and improving new treatment strategies. Here, we developed a novel rat model of CSDH using extracellular matrices (Matrigel) and brain microvascular endothelial cell line (bEnd.3 cells). One hundred-microliter of Matrigel-bEnd.3 cell (106 cells per milliliter) mixtures were injected into the virtual subdural space of elderly male Sprague-Dawley rats. This approach for the first time led to a spontaneous and expanding subdural hematoma, encapsulated by internal and external neomembranes, formed as early as 3 d, reached its peak at 7 d, and lasted for more than 14 d, mimicking the progressive hemorrhage observed in patients with CSDH. The external neomembrane and hematoma fluid involved numerous inflammatory cells, fibroblasts, and highly fragile neovessels. Furthermore, a localized pathophysiological process was validated as evidenced by the increased expressions of inflammatory and angiogenic mediators in external neomembrane and hematoma fluid rather than in peripheral blood. Notably, the specific expression profiles of these mediators were closely associated with the dynamic changes in hematoma volume and neurological outcome. In summary, the CSDH model described here replicated the characteristics of human CSDH, and might serve as an ideal translational platform for preclinical studies. Meanwhile, the crucial roles of angiogenesis and inflammation in CSDH formation were reaffirmed.

Uncovering sex differences of rodent microglia.

There are inherent structural and functional differences in the central nervous systems (CNS) of females and males. It has been gradually established that these sex-specific differences are due to a spectrum of genetic, epigenetic, and hormonal factors which actively contribute to the differential incidences, disease courses, and even outcomes of CNS diseases between sexes. Microglia, as principle resident macrophages in the CNS, play a crucial role in both CNS physiology and pathology. However, sex differences of microglia have been relatively unexplored until recently. Emerging data has convincingly demonstrated the existence of sex-dependent structural and functional differences of rodent microglia, consequently changing our current understanding of these versatile cells. In this review, we attempt to comprehensively outline the current advances revealing microglial sex differences in rodent and their potential implications for specific CNS diseases with a stark sex difference. A detailed understanding of molecular processes underlying microglial sex differences is of major importance in design of translational sex- and microglia-specific therapeutic approaches.

Atorvastatin combined with low-dose dexamethasone for vascular endothelial cell dysfunction induced by chronic subdural hematoma.

Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma. However, treatment with atorvastatin is not effective in some patients, who must undergo further surgical treatment. Dexamethasone has anti-inflammatory and immunomodulatory effects, and low dosages are safe and effective for the treatment of many diseases, such as ankylosing spondylitis and community-acquired pneumonia. However, the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood. Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group. Atorvastatin, dexamethasone, or their combination was added to the culture medium. The main results were as follows: hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1 µM atorvastatin and 0.1 µM dexamethasone. Atorvastatin, dexamethasone, or their combination could markedly improve the recovery of injured endothelial cells. Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin, dexamethasone, or their combination exhibited varying levels of rescue of endothelial cell function. Hopping probe ion conductance microscopy, western blot assay, and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin, dexamethasone, or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid. Moreover, the curative effect of the combined treatment was significantly better than that of either single treatment. Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased, as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group. Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells. However, atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury. The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone. Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma. The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31, 2016 (approval No. IRB2016-YX-036). The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31, 2018 (approval No. IRB2018-088-01).

Underestimated Peripheral Effects Following Pharmacological and Conditional Genetic Microglial Depletion.

Microglia, predominant parenchymal resident macrophages in the central nervous system (CNS), are crucial players in neurodevelopment and CNS homeostasis. In disease conditions, pro-inflammatory microglia predominate over their regulatory counterparts, and are thus a potential immunotherapeutic target. It has been well documented that microglia can be effectively depleted using both conditional genetic Cx3cr1Cre-diphtheria toxin receptor (DTR)/diphtheria toxin subunit A (DTA) animal models and pharmacological colony-stimulating factor 1 receptor (CSF1R) inhibitors. Recent advances using these approaches have expanded our knowledge of the multitude of tasks conducted by microglia in both homeostasis and diseases. Importantly, experimental microglial depletion has been proven to exert neuroprotective effects in an increasing number of disease models, mostly explained by reduced neuroinflammation. However, the comprehensive effects of additional targets such as circulating monocytes and peripheral tissue macrophages during microglial depletion periods have not been investigated widely, and for those studies addressing the issue the conclusions are mixed. In this study, we demonstrate that experimental microglial depletion using both Cx3cr1CreER/+Rosa26DTA/+ mice and different doses of CSF1R inhibitor PLX3397 exert crucial influences on circulating monocytes and peripheral tissue macrophages. Our results suggest that effects on peripheral immunity should be considered both in interpretation of microglial depletion studies, and especially in the potential translation of microglial depletion and replacement therapies.

Atorvastatin Combined with Low-Dose Dexamethasone Treatment Protects Endothelial Function Impaired by Chronic Subdural Hematoma via the Transcription Factor KLF-2.

OBJECTIVE: Our previous study showed that the combination therapy with atorvastatin and low-dose dexamethasone protected endothelial cell function in chronic subdural hematoma (CSDH) injury. In this study, we aimed to investigate the mechanism underlying the effects of this combination therapy on CSDH-induced cell dysfunction. METHODS: Monocytes and endothelial cells were cocultured with CSDH patient hematoma samples to mimic the pathological microenvironment of CSDH. Monocytes (THP-1 cells) and endothelial cells (hCMEC/D3 cells) were cocultured in a transwell system for 24 h before stimulation with hematoma samples diluted in endothelial cell medium (ECM) at a 1:1 ratio. Tight junction markers were detected by Western blotting, PCR and immunofluorescence. hCMEC/D3 cells were collected for Western blot and PCR analyses to detect changes in the expression levels of vascular cell adhesion molecule (VCAM-1), intercellular adhesion molecule (ICAM-1), and Kruppel-like factor 2 (KLF-2). The IL-6, IL-10 and VEGF levels in the supernatant were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: KLF-2 expression in endothelial cells was decreased after stimulation with CSDH patient hematoma samples, but combination therapy with atorvastatin and low-dose dexamethasone reversed this trend. KLF-2 protected injured cells by increasing the expression of VE-cadherin and ZO-1; attenuating the expression of VCAM-1, ICAM-1, IL-6 and VEGF; and enhancing the expression of IL-10, all of which play pivotal roles in endothelial inflammation. Moreover, the effect of combination therapy with atorvastatin and low-dose dexamethasone was obviously reduced in endothelial cells with KLF-2 knockdown compared with normal cells. CONCLUSION: Coculture with hematoma samples decreased KLF-2 expression in human cerebral endothelial cells. Combination therapy with atorvastatin and low-dose dexamethasone counteracted hematoma-induced KLF-2 suppression in human cerebral endothelial cells to attenuate robust endothelial inflammation and permeability. KLF-2 plays an important role in drug therapy for CSDH and may become the key factor in treatment and prognosis.

Dexmedetomidine attenuates endoplasmic reticulum stress-induced apoptosis and improves neuronal function after traumatic brain injury in mice.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide. Emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Dexmedetomidine (Dex), a highly selective α2-adrenoreceptor agonist, has been shown to attenuate ER stress. However, there is no relevant research in the field of TBI. To study the effects of dexmedetomidine on TBI, we subjected mice to TBI with a controlled cortical impact (CCI) device. The expression levels of ER stress marker proteins and apoptosis-related proteins were evaluated by western blotting and immunofluorescence. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labelling (TUNEL) assay. Neurological and motor deficits were assessed by modified neurological severity scores (mNSSs) and beam balance and beam walking tests. Brain water content and EB leakage were also assessed. Our group found that ER stress was significantly activated 72 h after TBI. Dexmedetomidine significantly reduced ER stress and ER stress-related neuronal apoptosis induced by experimental TBI. In addition, dexmedetomidine significantly improved neurological function and alleviated brain oedema. These findings indicate that dexmedetomidine alleviates severe, post-traumatic ER stress and attenuates secondary brain damage.

Semaphorin 3A Contributes to Secondary Blood-Brain Barrier Damage After Traumatic Brain Injury.

Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To investigate the effects of SEMA3A, we used a mouse TBI model with a controlled cortical impact (CCI) device and a blood-brain barrier (BBB) injury model in vitro with oxygen-glucose deprivation (OGD). We tested post-TBI changes in SEMA3A, and its related receptors (Nrp-1 and plexin-A1) expression and distribution through western blotting and double-immunofluorescence staining, respectively. Neurological outcomes were evaluated by modified neurological severity scores (mNSSs) and beam-walking test. We examined BBB damage through Evans Blue dye extravasation, brain water content, and western blotting for VE-cadherin and p-VE-cadherin in vivo, and we examined the endothelial cell barrier through hopping probe ion conductance microscopy (HPICM), transwell leakage, and western blotting for VE-cadherin and p-VE-cadherin in vitro. Changes in miR-30b-5p were assessed by RT-PCR. Finally, the neuroprotective function of miR-30b-5p is measured by brain water content, mNSSs and beam-walking test. SEMA3A expression varied following TBI and peaked on the third day which expressed approximate fourfold increase compared with sham group, with the protein concentrated at the lesion boundary. SEMA3A contributed to neurological function deficits and secondary BBB damage in vivo. Our results demonstrated that SEMA3A level following OGD injury almost doubled than control group, and the negative effects of OGD injury can be improved by blocking SEMA3A expression. Furthermore, the expression of miR-30b-5p decreased approximate 40% at the third day and 60% at the seventh day post-CCI. OGD injury also exhibited an effect to approximately decrease 50% of miR-30b-5p expression. Additionally, the expression of SEMA3A post-TBI is regulated by miR-30b-5p, and miR-30b-5p could improve neurological outcomes post-TBI efficiently. Our results demonstrate that SEMA3A is a significant factor in secondary BBB damage after TBI and can be abolished by miR-30b-5p, which represents a potential therapeutic target.

Significance of TERT and ATRX mutations in glioma.

Mutations of telomerase reverse transcriptase (TERT) and the α thalassemia/mental retardation syndrome X-linked (ATRX) genes have been the subject of numerous studies on the classification and prognosis of glioma. However, the association between TERT and ATRX in World Health Organization (WHO) grade II to IV glioma remains unclear. The present study utilized Sanger sequencing and immunohistochemical methods to detect the expression of the TERT promoter region, ATRX mutations and proliferation marker protein Ki-67 (Ki-67) protein expression in 179 cases of glioma. The current study analyzed these variables and their association with clinicopathological characteristics to further basic research and provide a theoretical basis for the clinical diagnosis and treatment of this type of tumor (1). The results demonstrated that TERT promoter mutations were negatively associated with ATRX. Additionally, Ki-67 protein expression in TERT wild-type samples was higher compared with samples with ATRX deletion. Overall, the results demonstrated, for the first time to the best of the authors' knowledge, that TERT promoter mutations are negatively associated with ATRX expression in WHO grade II to IV gliomas. These findings provide a theoretical basis for further basic research and may improve clinical diagnosis and treatment of glioma in the future.

Management of Dumbbell and Paraspinal Tumors of the Thoracic Spine Using a Single-stage Posterolateral Approach: Case Series.

This study investigated the surgical results of a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy for the management of dumbbell tumors and paraspinal tumors of the thoracic spine. From January 2010 to March 2017, 14 patients with dumbbell tumors or paraspinal tumors of the thoracic spine who underwent resection with single-stage posterolateral approach were followed up and analyzed retrospectively. The operations were performed using a single-stage posterolateral approach with arc incision, unilateral laminectomy, and costotransversectomy without any instrumentation. We reviewed the scores of clinical symptoms and imaging results, including postoperative MRI and reconstructed 3D-CT images. Gross total removal was achieved in 13 patients, and subtotal removal was achieved in 1 case. Histopathology revealed schwannoma in 9 patients, angiolipoma in 1 patient, and paraganglioma and mixed hemangioma in 2 patients each. No significant operative or postoperative complications occurred in any patient. The 14 patients were followed up for 14-68 months (mean 39.4 months). At the final follow-up, no obvious spinal deformity or tumor recurrence was found in any patient except one with paraganglioma. Single-stage posterolateral approach is a good alternative surgical method for removing dumbbell tumors and paraspinal tumors of the thoracic spine without necessitating a subsequent anterior operation.

Cognitive impairment after traumatic brain injury is associated with reduced long-term depression of excitatory postsynaptic potential in the rat hippocampal dentate gyrus.

Traumatic brain injury can cause loss of neuronal tissue, remote symptomatic epilepsy, and cognitive deficits. However, the mechanisms underlying the effects of traumatic brain injury are not yet clear. Hippocampal excitability is strongly correlated with cognitive dysfunction and remote symptomatic epilepsy. In this study, we examined the relationship between traumatic brain injury-induced neuronal loss and subsequent hippocampal regional excitability. We used hydraulic percussion to generate a rat model of traumatic brain injury. At 7 days after injury, the mean modified neurological severity score was 9.5, suggesting that the neurological function of the rats was remarkably impaired. Electrophysiology and immunocytochemical staining revealed increases in the slope of excitatory postsynaptic potentials and long-term depression (indicating weakened long-term inhibition), and the numbers of cholecystokinin and parvalbumin immunoreactive cells were clearly reduced in the rat hippocampal dentate gyrus. These results indicate that interneuronal loss and changes in excitability occurred in the hippocampal dentate gyrus. Thus, traumatic brain injury-induced loss of interneurons appears to be associated with reduced long-term depression in the hippocampal dentate gyrus.

Brain-derived microparticles activate microglia/macrophages and induce neuroinflammation.

Microparticles are cell fragments derived from damaged cells that are able to present an antigen from the parent cells to other cells to activate intracellular signaling pathways. Microparticles are closely related to the inflammatory response. Brain-derived microparticles (BDMPs) play an important role in brain injury. However, the inflammatory effect of BDMPs on microglia/macrophages remains unclear. The BDMPs were consumed by microglia/macrophages in vivo and in vitro. The BDMPs activated microglia/macrophages and changed their morphology in vitro. The BDMPs dysregulate the production of pro-inflammatory factors, suggesting that the effect of the BDMPs on microglia/macrophages is pro-inflammatory. In this study, we used flow cytometry, hopping probe ion conductance microscopy, immunofluorescence and other techniques to study the effect of brain-derived microparticle activation on microglia/macrophages that leads to neuroinflammation. BDMPs might be possible targets for the treatment of traumatic brain injury (TBI) changes after secondary nerve inflammation.

Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation.

Traumatic brain injury (TBI) is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER) stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI) device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS) and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.