Blood-Based Glutamate Scavengers Reverse Traumatic Brain Injury-Induced Synaptic Plasticity Disruption by Decreasing Glutamate Level in Hippocampus Interstitial Fluid, but Not Cerebral Spinal Fluid, In Vivo
机构：[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[2]Henan Key Laboratory of Neural Regeneration and Repairment, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China[3]China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China
Excessive glutamate release has been implicated as a major contributor to multiple post-traumatic brain injury (TBI) deficits, including neurodegeneration and cognitive impairment. Prior to the presence of behavior change, synaptic plasticity is rapidly and potently disrupted by TBI, which is believed to be relevant to inappropriately increased extracellular glutamate concentration and glutamatergic receptor activation. Acutely promoting brain glutamate clearance with a blood-based scavenging system, glutamate oxaloacetate transaminase (GOT), prevents the delayed inhibition of LTP post-TBI. Here, we report that repeated dosing of recombinant GOT type 1, with the glutamate co-substrate oxaloacetate, could induce a persistent enhancement of serum level of GOT and reverse the disruption of synaptic plasticity 4days after the induction of TBI in rats. Moreover, the change of glutamate level post-TBI presents a different timeframe in ventricular CSF and hippocampus interstitial fluid (ISF), and the application of rGOT may reverse the inhibition of LTP by decreasing the glutamate level in hippocampus ISF, but not ventricular CSF. Lastly, we found that the intervention did not significantly affect the total level of glutamate in the hippocampus as well as the expression of major glutamate transporters, EAAT1 and EAAT2. Overall, the present findings support the importance of clearance of glutamate post-TBI and provide new evidence of the mechanism of glutamate-induced LTP inhibition which leads to a development of evaluations, intervention, and reversion for post-TBI cognitive deficit.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81701085]; Henan Key Laboratory of Neural Regeneration [HNSJXF-2018-020]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M620833, 2018T110121]; Beijing Postdoctoral Research FoundationChina Postdoctoral Science Foundation [2017-zz-121]
第一作者机构：[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[2]Henan Key Laboratory of Neural Regeneration and Repairment, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China
通讯作者：
通讯机构：[1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[3]China National Clinical Research Center for Neurological Diseases (NCRC-ND), Beijing, China
推荐引用方式(GB/T 7714)：
Dainan Zhang,Meng Xiao,Long Wang,et al.Blood-Based Glutamate Scavengers Reverse Traumatic Brain Injury-Induced Synaptic Plasticity Disruption by Decreasing Glutamate Level in Hippocampus Interstitial Fluid, but Not Cerebral Spinal Fluid, In Vivo[J].NEUROTOXICITY RESEARCH.2019,35(2):360-372.doi:10.1007/s12640-018-9961-8.
APA：
Dainan Zhang,Meng Xiao,Long Wang&Wang Jia.(2019).Blood-Based Glutamate Scavengers Reverse Traumatic Brain Injury-Induced Synaptic Plasticity Disruption by Decreasing Glutamate Level in Hippocampus Interstitial Fluid, but Not Cerebral Spinal Fluid, In Vivo.NEUROTOXICITY RESEARCH,35,(2)
MLA：
Dainan Zhang,et al."Blood-Based Glutamate Scavengers Reverse Traumatic Brain Injury-Induced Synaptic Plasticity Disruption by Decreasing Glutamate Level in Hippocampus Interstitial Fluid, but Not Cerebral Spinal Fluid, In Vivo".NEUROTOXICITY RESEARCH 35..2(2019):360-372
