Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.

Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Mechanisms of hepatocellular carcinoma and challenges and opportunities for molecular targeted therapy

The incidence and mortality of hepatocellular carcinoma(HCC) have fallen dramatically in China and elsewhere over the past several decades. Nonetheless, HCC remains a major public health issue as one of the most common malignant tumors worldwide and one of the leading causes of death caused by cancer in China. Hepatocarcinogenesis is a very complex biological process associated with many environmental risk factors and factors in heredity, including abnormal activation of cellular and molecular signaling pathways such as Wnt/β-catenin, hedgehog, MAPK, AKT, and ERK signaling pathways, and the balance between the activation and inactivation of the proto-oncogenes and anti-oncogenes, and the differentiation of liver cancer stem cells. Molecule-targeted therapy, a new approach for the treatment of liver cancer, blocks the growth of cancer cells by interfering with the molecules required for carcinogenesis and tumor growth, making it both specific and selective. However, there is no one drug completely designed for liver cancer, and further development in the research of liver cancer targeted drugs is now almost stagnant. The purpose of this review is to discuss recent advances in our understanding of the molecular mechanisms underlying the development of HCC and in the development of novel strategies for cancer therapeutics.

Regulatory mechanisms,prophylaxis and treatment of vascular leakage following severe trauma and shock

Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS), and has become one of the most important causes of death for intensive care units(ICU) patients. Currently, although there has been some progress in knowledge of the pathogenesis of these vascular disorders, the detailed mechanisms remain unclear, and effective prophylaxis and treatment are still lacking. In this study, we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock, which could be beneficial for the overall clinical treatment of vascular leakage disorders.

Differentiation and tumorigenicity of neural stem cells from human cord blood mesenchymal stem cells

BACKGROUND： Mesenchymal stem cells （MSCs） are capable of differentiating into a variety of tissues and exhibit low immunogenicity. OBJECTIVE： To investigate isolation and in vitro cultivation methods of human cord blood MSCs, to observe expression of neural stem cell （NSC） marker mRNA under induction, and to detect tumorigenicity in animals. DESIGN, TIME AND SETTING： A cell biological, in vitro trial and a randomized, controlled, in vivo experiment were performed at the Department of Neurology, Daping Hospital at the Third Military Medical University of Chinese PLA from August 2006 to May 2008. MATERIALS： Umbilical cord blood was collected from full-term-delivery fetus at the Department of Gynecology and Obstetrics of Daping Hospital, China. Eighteen BALB/C nu/nu nude mice were randomly assigned to three groups： back subcutaneous, cervical subcutaneous, and control, with 6 mice in each group. METHODS： Monocytes were isolated from heparinized human cord blood samples by density gradient centrifugation and then adherent cultivated in vitro to obtain MSC clones. After the cord blood MSCs were cultured for 7 days with nerve growth factor and retinoic acid to induce differentiation into NSCs, the cells （adjusted density of 1 × 10^7/mL） were prepared into cell suspension. In the back subcutaneous and cervical subcutaneous groups, nude mice were hypodermically injected with a 0.5-mL cell suspension into the back and cervical regions, respectively. In the control group, nude mice received a subcutaneous injection of 0.5 mL physiological saline into the back or cervical regions, respectively. MAIN OUTCOME MEASURES： Cellular morphology was observed by inverted microscopy, cultured cord blood MSCs were examined by flow cytometry, expression of nestin and musashi-1 mRNA was detected by reverse-transcriptase polymerase chain reaction prior to and after induction, and tumorigenicity following cord blood MSC transplantation was assayed by hematoxylin-eosin staining. RESULTS： Following adherent cultivation, the majority of cord blood monocytes became rhombic and strongly expressed CD29, but not CD34, CD1 la, or CD11 b. These results supported previously known characteristics of cord blood MSCs. Following differentiation induction, nestin and musashi-1 were expressed on the surface of NSCs, exhibiting strongest expression at 48 hours, and subsequently reducing expression. Cultured cord blood MSCs were not tumorigenic in the nude mice. Cellular morphology displayed no malignant changes between the control and subcutaneous groups. CONCLUSION： MSCs can be isolated from human cord blood, efficiently expanded under culture conditions, differentiated into NSCs following induction, and display no tumorigenicity in nude mice.

Incidence, casualties and risk characteristics of civilian explosion blast injury in China: 2000-2017 data from the State Administration of Work Safety

Background: Civilian explosion blast injury is more frequent in developing countries, including China. However, the incidence, casualties, and characteristics of such incidents in China are unknown.Methods: This is a retrospective analysis of the State Administration of Work Safety database. Incidents during a period from January 1, 2000 to April 30, 2017 were included in the analysis. The explosions were classified based on the number of deaths into extraordinarily major, major, serious and ordinary type. Descriptive statistics was used to analyze the incidence and characteristics of the explosions. Correlation analysis was performed to examine the potential correlations among various variables.Results: Data base search identified a total of 2098 explosions from 2000 to 2017, with 29,579 casualties: 15,788 deaths(53.4%), 12,637 injured(42.7%) and 1154 missing(3.9%). Majority of the explosions were serious type(65.4%). The number of deaths(39.5%) was also highest with the serious type(P=0.006). The highest incidence was observed in the fourth quarter of the year(October to December), and at 9:00–11:00 am and 4:00–6:00 pm of the day. The explosions were most frequent in coal-producing provinces(Guizhou and Shanxi Province). Coal mine gas explosions resulted majority of the deaths(9620, 60.9%). The number of explosion accidents closely correlated with economic output(regional economy and national GDP growth rate)(r=–0.372, P=0.040;r=0.629, P=0.028).Conclusions: The incidence and civilian casualties due to explosions remain unacceptable in developing China. Measures that mitigate the risk factors are of urgently required.

Effect of valproic acid on endogenous neural stem cell proliferation in a rat model of spinal cord injury

BACKGROUND： Valproic acid has been reported to decrease apoptosis, promote neuronal differentiation of brain-derived neural stem cells, and inhibit glial differentiation of brain-derived neural stem cells. OBJECTIVE： To investigate the effects of valproic acid on proliferation of endogenous neural stem cells in a rat model of spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, neuropathological study was performed at Key Laboratory of Trauma, Buming, and Combined Injury, Research Institute of Surgery, Daping Hospital, the Third Military Medical University of Chinese PLA between November 2005 and February 2007. MATERIALS： A total of 45 adult, Wistar rats were randomly divided into sham surgery （n = 5）, injury （n = 20）, and valproic acid （n = 20） groups. Valproic acid was provided by Sigma, USA. METHODS： Injury was induced to the T10 segment in the injury and valproic acid groups using the metal weight-dropping method. The spinal cord was exposed without contusion in the sham surgery group. Rats in the valproic acid group were intraperitoneally injected with 150 mg/kg valproic acid every 12 hours （twice in total）.MAIN OUTCOME MEASURES： Nestin expression （5 mm from injured center） was detected using immunohistochemistry at 1,3 days, 1, 4, and 8 weeks post-injury. RESULTS： Low expression of nestin was observed in the cytoplasm, but rarely in the white matter of the spinal cord in the sham surgery group. In the injury group, nestin expression was observed in the ependyma and pia mater one day after injury, and expression reached a peak at 1 week （P 〈 0.05）. Expression was primarily observed in the ependymal cells, which expanded towards the white and gray matter of the spinal cord. Nestin expression rapidly decreased by 4 weeks post-injury, and had almost completely disappeared by 8 weeks. At 24 hours after spinal cord injury, there was no significant difference in nestin expression between the valproic acid and injury groups. At 1 week, there was a significant increase in the number of nestin-positive cells surrounding the central canal in valproic acid group compared with the injury group （P 〈 0.05）. Expression reached a peak by 4 weeks, and it was still present at 8 weeks. CONCLUSION： Valproic acid promoted endogenous neural stem cell proliferation following spinal cord injury in rats.

Exploration of the glutamate-mediated retinal excitotoxic damage: a rat model of retinal neurodegeneration

AIM： To explore the more suitable concentration of glutamate or N-methyl-D-aspartic acid（NMDA） for intravitreal injection to establish a rat model of retinal neurodegeneration. METHODS： We injected different doses of glutamate（20 or 50 nmol） or NMDA（40 nmol） into the vitreous chambers of rats, then measured the concentration of glutamate and retinal thickness, quantified apoptotic cells and determined the degree of tau hyperphosphorylation at different time points. T-test was used for comparison of two groups. One-way ANOVA and Turkey＇s multiple comparisons test were used for comparisons of different groups, and P values below 0.05 were considered statistically significant.RESULTS： The glutamate level in the rats treated with 50 nmol of glutamate was twice that of the control group and persisted two weeks. Seven days after intravitreal injection of 50 nmol of glutamate, three parameters [inner retinal thickness（IRT）, retinal thickness（RT） and ganglion cell layer（GCL） cell number] were reduced significantly. Furthermore, numerous TUNEL-positive cells were observed in the GCL one day after intravitreal injection of 50 nmol of glutamate, the expression of the apoptosisrelated factor cleaved casepase-3 was markedly increased compared with the expression levels in the other treatment groups, and the expression levels of tau s396 and tau s404 were significantly increased compared with those in the control group.CONCLUSION： This study demonstrates that the intravitreal injection of 50 nmol of glutamate can establish the more effective retinal neurodegeneration animal model relative to other treatment groups.

Logistic regression analysis on risk factors for vascular dementia following cerebral infarction in 403 patients from Chongqing City Hospital and family follow-up studies

BACKGROUND： Studies have demonstrated that the risk factors of vascular dementia following stroke are greatly different in region, race and other aspects. OBJECTIVE： To analyze the conditions and incidental risk factors of vascular dementia in patients with acute cerebral infarction from Chongqing City. DESIGN： Case analysis. SETTING： Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA. PARTICIPANTS： Altogether 546 inpatients with acute ischemic stroke admitted to Department of Neurology, Daping Hospital, Third Military Medical University of Chinese PLA between May 1999 and December 2002 were involved in this study. The involved patients, including 295 males and 251 females, aged 55 - 94 years, dwelled in Chongqing over 5 years. They were admitted to hospital within 48 hours of attack of acute ischemic stroke, and survived for over 3 months. Informed consents were obtained from all the involved subjects. METHODS： ① Following the same standard, cognitive and social function evaluations were conducted by one physician on admission and 3 months after admission, Unified questionnaire, consisting of general characteristics, vascular risk factors, stroke characteristics, neurological physical sign, and other 28 factors of involved subjects, was used in all the patients. According to the investigation results, the patients were assigned into 2 groups： dementia group and non-dementia group. ②Ischemic stroke was diagnosed according to acute ischemic brain disorder 〉 24 hours and CT or MRI imageology.③ Neurophysiological examination was conducted in all the patients at 7 to l0 days after stroke （score was two SD less than or equaled to normal level was considered as abnormal）. ④Diagnosis and statistics of dementia were carried out with Mini-Mental State Examination and The Diagnostic and Statistical Manual of Mental Disorders-Ⅳ （published by American Psychiatric Association） on admission and 3 months after admission. Neurologic deficit scoring was carried out with the National Institutes of Health Stroke Scale. ⑤ Chi-square test was used for categorical variable, and t test for quantitative variable between dementia group and non-dementia group. Dementia-related factors were performed multiple-factor Logistic regression model analysis. MAIN OUTCOME MEASURES： Incidence of dementia and dementia-related risk factors of patients. RESULTS： Altogether 546 patients with stroke were involved in this study, 403 of them participated in the final analysis, and 143 dropped out. A total of 342 were followed-up in the hospital and 61 at home. At 3 months after cerebral infarction, vascular dementia occurred in 87 （21.6%） of 403 patients. The main risk factors were age （OR 1.179; 95%CI 1.130 - 1.230）, low education level （OR 1.806; 95%CI 1.024 - 3.186）, daily alcohol drinking （OR 3.447; 95%（1/ 1.591 - 7.468）, stroke history （OR 2.531; 95%CI 1.419 - 4.512）, atrial fibrilation（OR 3.475; 95%CI 1.712 - 7.057）, dysphonia （OR 5.873; 95%6/2.620 - 13.163） and left carotid artery infarction （OR 1.975; 95%（1/1.152 - 3.388）. CONCLUSION： The incidence of vascular dementia is determined by synthetic action of multiple risk factors. Dysphonia is the most important influencing factor.

Inhibition of aberrant Hif1αactivation delays intervertebral disc degeneration in adult mice

The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

Early prevention of trauma-related infection/sepsis

Trauma still represents one of the major causes of death worldwide. Despite the reduction of post-traumatic sepsis over the past two decades, the mortality of septic trauma inpatients is still high(19.5%–23.0%). Early prevention of sepsis development can aid in the subsequent treatment of patients and help improve their outcomes. To date, the prevention of trauma-related infection/sepsis has mainly included infection prevention(e.g., surgical management, prophylactic antibiotics, tetanus vaccination, immunomodulatory interventions) and organ dysfunction prevention(e.g., pharmaceuticals, temporary intravascular shunts, lung-protective strategies, enteral immunonutrition, acupuncture). Overall, more efficient ways should be developed to prevent trauma-related infection/sepsis.

Chinese expert consensus on echelons treatment of pelvic fractures in modern war

The characteristics and treatment of pelvic fractures vary between general conditions and modern war. An expert consensus has been reached based on pelvic injury epidemiology and the concepts of battlefield treatment combined with the existing levels of military medical care in modern warfare. According to this consensus, first aid, emergency treatment and early treatment of pelvic fractures are introduced in three separate levels. In Level Ⅰ facilities, simple triage and rapid treatment following the principles of advanced trauma life support are recommended to evaluate combat casualties during the first-aid stage. Re-evaluation, further immobilization and fixation, and hemostasis are recommended at Level Ⅱ facilities. At Level Ⅲ facilities, the main components of damage control surgery are recommended, including comprehensive hemostasis, a proper resuscitation strategy, the treatment of concurrent visceral and blood vessel damage, and battlefield intensive care. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.

Effects of high dose glucocorticoid on expression and mRNA transcription of corticotropin releasing hormone in hypothalamus paraventricular nucleus of rats

Objective： To explore the effect of high dose of glucocorticoid （GC） on the synthesis of corticotropin releasing hormone （CRH） and transcription of its mRNA in hypothalamus paraventricular nuclei （PVN） in order to investigate its difference with that of traditional GC effects and to add a new possible explanation to the mechanism of clinical applications of high dose of GC. Methods： A total of 60 rats were divided into 5 groups： blank control, 10^-6 mol/L dexamethasone （DEX） group, 10^-9 mol/L DEX group, 0.9% saline group and GR blocking group （10^-2mol/L RU486）. All agents were administrated through the femoral vein. CRH protein expression was measured by immunohistochemistry and laser confocal scanning microscopy （LCSM）; CRH mRNA level was explored by in situ hybridization. Results： 10^-6 mol/L DEX made CRH mRNA transcripted after 20 min and its protein expressed in PVN after 30 min, while normal level of DEX and 0.9% saline could not. If GR was blocked in advance, the effect of high dose of DEX disappeared. Conclusion ： High dose of GC can have CRH increased in PVN, which differs to the effect of traditional GC. And mGRH may play an important role in the effect of high dose of GC but not classic iGR.

Overview of Wound Features and Treatment in Wenchuan Earthquake Victims

Objective: “5.12” Wenchuan Earthquake killed 70,000 people and left more than 90,000 people injured seriously. This study was to analyze the wound features and early treatments in Wenchuan earthquake victims and investigate treatment strategies in major disasters, to provide a reference to future disaster rescue. Methods: Total of 1420 earthquake patients who were admitted to Deyang People’s Hospital, Sichuan Province from May 12-30, 2008 were enrolled in the study. The wound features and early treatment were retrospectively analyzed. Results: Among 1420 patients, there were total 1821 injuries. In which, there were 1089 cases with single site injury (76.69%) and 331 cases with multiple injury (23.31%);injuries of limb, body surface and soft tissue were more than that of other sites;injury of single site was larger than that of multi-site (P < 0.01);most of the earthquake patients were admitted to hospital within 2 days after earthquake (68.80%), whose number was more than those at other times (P < 0.01);the number of the earthquake patients in 19 - 45 age group was more than that of other groups (P < 0.01);most of patients were treated within 12 hours after injury (P < 0.01). Conclusion: In disaster rescue, rescue speed is the key point. And the “golden time” and emphases of rescue should be within 2 days after earthquake;the principle of damage control surgery should be followed in the rescue. Enhancing mutual and self help practice and first-aid training at usual times may save more lives.

Radiotherapy for Lowly Malignant Cranial Inflammatory Myofibroblastic Tumor Accompanied with Intracranial Invasion:Case Report and Literature Review

Inflammatory myofibroblastic tumor(IMT) is rare in clinical practice.As its treatment mainly involves surgery,radiotherapy alone is seldom reported in literature.Here we report a case of lowly malignant cranial IMT with intracranial invasion in a female patient. As surgery was not suitable,intensity modulated radiation therapy(IMRT) was administered.After radiotherapy,the cranial lesions tended to show efficacy.

Comparative Study on the Trans-Province Transfer of the Multiple Trauma Patients after Sichuan Earthquake

Background: Trans-province transfer of the patients has been successfully carried out and has greatly relieved the burden of the hospitals in Sichuan Province after Sichuan earthquake. The aim of the study was to retrospectively analyze the efficacy and feasibility of the trans-province transfer of the multiple trauma patients after Sichuan earthquake. Methods: A retrospective and descriptive analysis was conducted based on the medical records of the multiple trauma patients (ISS ≥ 16) transferred to the Grade 3A hospitals outside Sichuan province. The patients were divided into two groups based on the distance to Sichuan province, i.e., Group A (the seismic patients transferred to Chongqing) and Group B (the seismic patients transferred to the other provinces/ municipalities). A comparison was done in aspects of distance of transfer, time from injury to transfer, vital signs, the infection rates (at transfer and on discharge), injury severity and prognostic indices (cure rate, disability rate and mortality). Results: The distance between Chengdu and the other places was at a wide range of 313 - 1653 km, whereas the time from injury to transfer showed no statistical difference between groups (P > 0.05). There were no significant differences between both groups with respects to patient demographics, injury mechanism, time from injury to transfer, vital signs, infection rate and injury severity. The prognostic indices showed no significant difference, except for FIM scores (P < 0.05). Conclusions: The results of the study indicate that the different distance of the transfer of the multiple trauma patients does not aggravate the severity or deteriorate the prognosis, which proves that the medical supportive transfer system is acceptable, effective and worthy of further implementation in China, which may be ascribed to the advanced transportation system and high level of therapeutic capacity of the hospitals. In the meantime, attention should be paid to psychological intervention and functional rehabilitation during the treatment of the transferred seismic patients.

Exosomes: roles and therapeutic potential in osteoarthritis

Exosomes participate in many physiological and pathological processes by regulating cell–cell communication, which are involved in numerous diseases, including osteoarthritis(OA). Exosomes are detectable in the human articular cavity and were observed to change with OA progression. Several joint cells, including chondrocytes, synovial fibroblasts, osteoblasts, and tenocytes, can produce and secrete exosomes that influence the biological effects of targeted cells. In addition, exosomes from stem cells can protect the OA joint from damage by promoting cartilage repair, inhibiting synovitis, and mediating subchondral bone remodeling.This review summarizes the roles and therapeutic potential of exosomes in OA and discusses the perspectives and challenges related to exosome-based treatment for OA patients in the future.

An open air research study of blast-induced traumatic brain injury to goats

Purpose： we once reported blast-induced traumatic brain injury （bTBI） in confined space. Here, bTBI was studied again on goats in the open air using 3.0 kg trinitrotoluene. Methods： The goats were placed at 2, 4, 6 and 8 m far from explosion center. Trinitrotoluene （TNT） was used as the source of the blast wave and the pressure at each distance was recorded. The systemic physiology, electroencephalogram, serum level of S-100beta, and neuron specific enolase （NSE） were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 h after the exposure. Results： Simple blast waveforms were recorded with parameters of 702.8 kPa-0.442 ms, 148.4 kPa- 2.503 ms, 73.9 kPa-3.233 ms, and 41.9 kPa-5.898 ms at 2, 4, 6 and 8 m respectively. Encephalic blast overpressure was on the first time recorded in the literature by us at 104.2 kPa-0.60 ms at 2 m, where mortality and burn rate were 44% and 44%. Gross examination showed that bTBI was mainly manifested as congestive expansion of blood vessels and subarachnoid hemorrhage, which had a total incidence of 25% and 19% in 36 goats. Microscopical observation found that the main pathohistological changes were enlarged perivascular space （21/36, 58%）, small hemorrhages （9/36, 25%）, vascular dilatation and congestion （8/36, 22%）, and less subarachnoid hemorrhage （2[36, 6%）. After explosion, serum levels of S- 10013 and NSE were elevated, and EEG changed into slow frequency with declined amplitude. The results indicated that severity and incidence of bTBI is related to the intensity of blast overpressure. Conclusion： Blast wave can pass through the skull to directly injure brain tissue.