Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the im...Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.展开更多
Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ...Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.展开更多
Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellul...Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.展开更多
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of...Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.展开更多
Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell p...Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.展开更多
AIM: To detect the expression of sal-like protein 4 (SALL4) and to explore its relationship with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC).METHODS: One hundred and twenty-six ...AIM: To detect the expression of sal-like protein 4 (SALL4) and to explore its relationship with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC).METHODS: One hundred and twenty-six samples of HCC tissue, 44 of adjacent noncancerous cirrhotic tissue and 10 of liver hemangioma tissue, were obtained from patients who underwent hepatectomy for HCC at the Fourth Hospital of Hebei Medical University. None of the patients had received any form of treatment before the operation. After resection, all the tissues were fixed in 10% neutral formaldehyde and embedded in paraffin. Expression of SALL4 was detected by immunohistochemistry. Patients were followed up for postoperative survival until February 2014. The relationships between SALL4 expression level and clinicopathological data and prognosis of HCC were analyzed.RESULTS: SALL4 expression was negative in the 10 samples of tissue from liver hemangioma, was weakly positive in the two samples from adjacent noncancerous cirrhotic tissue, and positive in 58 samples of HCC tissues. The differences were statistically significant (P < 0.05). Expression of SALL4 was higher in patients with higher α-fetoprotein (AFP) levels, portal vein tumor thrombus, and later clinical stage based on the Barcelona Clinic Liver Cancer classification (P < 0.05). Among patients with negative expression, weakly positive expression, positive expression, and strongly positive expression of SALL4, the median survival time was 39, 25, 23, and 9 mo, respectively (P < 0.001). When both AFP and SALL4 were detected, patients who were negative for both AFP and SALL4, SALL4-positive only, AFP-positive only, and positive for both AFP and SALL4, had a median survival time of 41, 38, 31, and 12 mo, respectively (P < 0.001).CONCLUSION: Expression of SALL4 is relevant to the prognosis of HCC patients. Patients with higher expression levels of SALL4 and AFP have worse prognosis.展开更多
Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferr...Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferroptosis,a novel form of regulated cell death characterized by iron-driven lipid peroxidation,was comprehensively activated in liver tissues from MAFLD patients.The canonical-GPX4(cGPX4),which is the most important negative controller of ferroptosis,is downregulated at protein but not mRNA level.Interestingly,a non-canonical GPX4 transcript-variant is induced(inducible-GPX4,iGPX4)in MAFLD condition.The high fat-fructose/sucrose diet(HFFD)and methionine/choline-deficient diet(MCD)-induced MAFLD pathologies,including hepatocellular ballooning,steatohepatitis andfibrosis,were attenuated and aggravated,respectively,in cGPX4-and iGPX4-knockin mice.cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes.Knockdown of iGPX4 by siRNA alleviated lipid stress,ferroptosis and cell injury.Mechanistically,the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress,and thus promotes ferroptosis.Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4.Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis,and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.展开更多
Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE ...Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE remains unclear.The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury(TBI),as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.Methods:The adult male Wistar rats we divided into a sham group and a TBI group,the latter of which was further divided into 1,3,6,12,24 and 72 hours(h)and 15 days(d)post injury subgroups.A proper TBI model was established,and brain edema was assessed in each group by water content.We measured the abundance of various proteins,including hypoxia inducible factor-1α(HIF-1α),AQP4,microtubule-associated protein 2(MAP2),tau-5 protein,phosphorylated level of TAU,synaptophysin,cyclic adenosine monophosphate response element binding protein(CREB),phosphorylated CREB and general control nonrepressed 2,in each group.Hippocampal neurons and spatial memory test were analyzed in different time points.Results:Compared with that in the sham group,the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI.During this time frame,AQP4 level peaked at 12 and 72 h,and these peaks were closely correlated with high brain water content.HIF-1αdisplayed a similar trend.Conversely,levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI.In addition,the most severe brain edema in rats was found at 24 h post TBI,with neuronal loss and hippocampal dendritic spine injury.Compared to those in the sham group,rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.Conclusions:AQP4 level was closely correlated with severity of brain edema,and abnormal levels thereof aggravated such severity after TBI.展开更多
文摘Different approaches for treating lung cancer have been developed over time, including chemotherapy, radiotherapy and targeted therapies against activating mutations. Lately, better understanding of the role of the immunological system in tumor control has opened multiple doors to implement different strategies to enhance immune response against cancer cells. It is known that tumor cells elude immune response by several mechanisms. The development of monoclonal antibodies against the checkpoint inhibitor programmed cell death protein 1 （PD-1） and its ligand （PD-L1）, on T cells, has led to high activity in cancer patients with long lasting responses. Nivolumab, an anti PD-1 inhibitor, has been recently approved for the treatment of squamous cell lung cancer patients, given the survival advantage demonstrated in a phase III trial. Pembrolizumab~ another anti PD-1 antibod）5 has received FDA breakthrough therapy designation for treatment of non-small cell lung cancer （NSCLC）, supported by data from a phase I trial. Clinical trials with anti PD-1/PD-L1 antibodies in NSCLC have demonstrated very good tolerability and activity, with response rates around 20% and a median duration of response of 18 months.
基金supported by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science(grant number:17K10825)to HS
文摘Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China(Nos.81430072,81421003,81602641,81572929).
文摘Background:Gastric cancer(GC)is one of the most common malignancies worldwide,particularly in China.DNA damage-inducible transcript 4(DDIT4)is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses;however,its critical role in GC remains poorly understood.The present study aimed to investigate the poten-tial relationship and the underlying mechanism between DDIT4 and GC development.Methods:We used western blotting,real-time polymerase chain reaction,and immunohistochemical or immunoflu-orescence to determine DDIT4 expression in GC cells and tissues.High-content screening,cell counting kit-8 assays,colony formation,and in vivo tumorigenesis assays were performed to evaluate cell proliferation.Flow cytometry was used to investigate cell apoptosis and cell cycle distribution.Results:DDIT4 was upregulated in GC cells and tissue.Furthermore,downregulating DDIT4 in GC cells inhibited proliferation both in vitro and in vivo and increased 5-fluorouracil-induced apoptosis and cell cycle arrest.In contrast,ectopic expression of DDIT4 in normal gastric epithelial cells promoted proliferation and attenuated chemosensitivity.Further analysis indicated that the mitogen-activated protein kinase and p53 signaling pathways were involved in the suppression of proliferation,and increased chemosensitivity upon DDIT4 downregulation.Conclusion:DDIT4 promotes GC proliferation and tumorigenesis,providing new insights into the role of DDIT4 in the tumorigenesis of human GC.
基金Supported by "Instituto de Salud Carlos Ⅲ",Spain& "European Regional Development Fund(ERDF)a way of making Europe",No.PI12/00130 and No.PI15/00074and"Gilead Spain&Instituto de Salud Carlos Ⅲ",No.GLD14_00217
文摘Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8<sup>+</sup> T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8<sup>+</sup> T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.
基金National Nature Science Foundation for Distinguished Young Scholar of China (No.39525022)National Basic Research Program(No.2004CB518703) National Nature Science Foundation of China (No.30570085).
文摘Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
基金Supported by the National Natural Science Foundation of China,No.81072966/H2902the Natural Science Foundation of Hebei Province,China,No.C2011206134
文摘AIM: To detect the expression of sal-like protein 4 (SALL4) and to explore its relationship with clinicopathological characteristics and prognosis of hepatocellular carcinoma (HCC).METHODS: One hundred and twenty-six samples of HCC tissue, 44 of adjacent noncancerous cirrhotic tissue and 10 of liver hemangioma tissue, were obtained from patients who underwent hepatectomy for HCC at the Fourth Hospital of Hebei Medical University. None of the patients had received any form of treatment before the operation. After resection, all the tissues were fixed in 10% neutral formaldehyde and embedded in paraffin. Expression of SALL4 was detected by immunohistochemistry. Patients were followed up for postoperative survival until February 2014. The relationships between SALL4 expression level and clinicopathological data and prognosis of HCC were analyzed.RESULTS: SALL4 expression was negative in the 10 samples of tissue from liver hemangioma, was weakly positive in the two samples from adjacent noncancerous cirrhotic tissue, and positive in 58 samples of HCC tissues. The differences were statistically significant (P < 0.05). Expression of SALL4 was higher in patients with higher α-fetoprotein (AFP) levels, portal vein tumor thrombus, and later clinical stage based on the Barcelona Clinic Liver Cancer classification (P < 0.05). Among patients with negative expression, weakly positive expression, positive expression, and strongly positive expression of SALL4, the median survival time was 39, 25, 23, and 9 mo, respectively (P < 0.001). When both AFP and SALL4 were detected, patients who were negative for both AFP and SALL4, SALL4-positive only, AFP-positive only, and positive for both AFP and SALL4, had a median survival time of 41, 38, 31, and 12 mo, respectively (P < 0.001).CONCLUSION: Expression of SALL4 is relevant to the prognosis of HCC patients. Patients with higher expression levels of SALL4 and AFP have worse prognosis.
基金supported by the grants from National Natural Science Foundation of China (82073915, 91849135, 81673485, 81773719, 81973312 and 81971306)National Key Research and Development Project (2018YFA0108301, China)+2 种基金Shanghai Science and Technology Commission Experimental Animal Grants (21XD1424900, 19140904700, 19140904900 and 21S11901200, China)Shanghai Shuguang Program (19SG32, China)Shanghai “Rising Stars of Medical Talent” Youth Development ProgramYouth Medical Talents-Clinical Pharmacist Program [SHWRS(2020)_087, China]
文摘Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferroptosis,a novel form of regulated cell death characterized by iron-driven lipid peroxidation,was comprehensively activated in liver tissues from MAFLD patients.The canonical-GPX4(cGPX4),which is the most important negative controller of ferroptosis,is downregulated at protein but not mRNA level.Interestingly,a non-canonical GPX4 transcript-variant is induced(inducible-GPX4,iGPX4)in MAFLD condition.The high fat-fructose/sucrose diet(HFFD)and methionine/choline-deficient diet(MCD)-induced MAFLD pathologies,including hepatocellular ballooning,steatohepatitis andfibrosis,were attenuated and aggravated,respectively,in cGPX4-and iGPX4-knockin mice.cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes.Knockdown of iGPX4 by siRNA alleviated lipid stress,ferroptosis and cell injury.Mechanistically,the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress,and thus promotes ferroptosis.Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4.Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis,and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.
文摘Background:Traumatic brain edema(TBE)is caused by a specific water channel mediated by membrane aquaporins.Aquaporin-4(AQP4)plays an especially important role in this process,but the relationship between AQP4 and TBE remains unclear.The purpose of this study was to explore expression of AQP4 in the hippocampus after traumatic brain injury(TBI),as well as the effect of brain edema on skeletal protein and its function in hippocampal neurons.Methods:The adult male Wistar rats we divided into a sham group and a TBI group,the latter of which was further divided into 1,3,6,12,24 and 72 hours(h)and 15 days(d)post injury subgroups.A proper TBI model was established,and brain edema was assessed in each group by water content.We measured the abundance of various proteins,including hypoxia inducible factor-1α(HIF-1α),AQP4,microtubule-associated protein 2(MAP2),tau-5 protein,phosphorylated level of TAU,synaptophysin,cyclic adenosine monophosphate response element binding protein(CREB),phosphorylated CREB and general control nonrepressed 2,in each group.Hippocampal neurons and spatial memory test were analyzed in different time points.Results:Compared with that in the sham group,the level of AQP4 in hippocampal neurons began to significantly increase at 1 h post TBI and then decreased at 15 d post TBI.During this time frame,AQP4 level peaked at 12 and 72 h,and these peaks were closely correlated with high brain water content.HIF-1αdisplayed a similar trend.Conversely,levels of MAP2 began to decrease at 1 h post TBI and then increase at 15 d post TBI.In addition,the most severe brain edema in rats was found at 24 h post TBI,with neuronal loss and hippocampal dendritic spine injury.Compared to those in the sham group,rats in the TBI groups had significantly prolonged latency and significantly shortened exploration time.Conclusions:AQP4 level was closely correlated with severity of brain edema,and abnormal levels thereof aggravated such severity after TBI.
