Neurotoxicity Research

, Volume 35, Issue 2, pp 360–372 | Cite as

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

  • Dainan Zhang
  • Meng Xiao
  • Long Wang
  • Wang JiaEmail author


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 4 days 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.


Traumatic brain injury Hippocampus Glutamate-oxaloacetate transaminase Synaptic plasticity Long-term potentiation 



Cornu ammonis


Cerebral spinal fluid


Dimethyl sulfoxide


Field excitatory post-synaptic potential


Glutamate oxaloacetate transaminase


High-frequency stimulation






Interstitial fluid


Long-term depression


Long-term potentiation


Metabotropic glutamate








Standard error of the mean


Traumatic brain injury


Author’s Contributions

D.Z. performed experiments, interpreted data, and drafted the manuscript. M.X. and L.W. performed experiments. W.J. designed and supervised this study and edited the manuscript.

Funding Information

This study was supported by the National Natural Science Foundation of China (no. 81701085), Henan Key Laboratory of Neural Regeneration and Repairment (no. HNSJXF-2018-020), China Postdoctoral Science Foundation (no. 2017M620833 and no. 2018T110121), and Beijing Postdoctoral Research Foundation (no. 2017-zz-121).

Compliance with Ethical Standards

The animal care and experimental protocol were performed according to the guidelines of the Guidance for Animal Experimentation of the Capital Medical University, and the protocol was approved by the Experimental Animal Ethics Committee of the Beijing Tiantan Hospital, Capital Medical University.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Dainan Zhang
    • 1
    • 2
  • Meng Xiao
    • 2
  • Long Wang
    • 2
  • Wang Jia
    • 1
    • 3
    Email author
  1. 1.Department of Neurosurgery, Beijing Tiantan HospitalCapital Medical UniversityBeijingChina
  2. 2.Henan Key Laboratory of Neural Regeneration and RepairmentThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiChina
  3. 3.China National Clinical Research Center for Neurological Diseases (NCRC-ND)BeijingChina

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