Extracellular Glutamate Concentration Increases Linearly in Proportion to Decreases in Residual Cerebral Blood Flow after the Loss of Membrane Potential in a Rat Model of Ischemia

Hirokazu Kawase, Yoshimasa Takeda, Ryoichi Mizoue, Sachiko Sato, Miki Fushimi, Satoshi Murai, Hiroshi Morimatsu

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Background: Brain ischemia due to disruption of cerebral blood flow (CBF) results in increases in extracellular glutamate concentration and neuronal cell damage. However, the impact of CBF on glutamate dynamics after the loss of the membrane potential remains unknown. Materials and Methods: To determine this impact, we measured extracellular potential, CBF, and extracellular glutamate concentration in the parietal cortex in male Sprague-Dawley rats (n=21). CBF was reduced by bilateral occlusion of the common carotid arteries and exsanguination until loss of extracellular membrane potential was observed (low-flow group), or until CBF was further reduced by 5% to 10% of preischemia levels (severe-low-flow group). CBF was promptly restored 10 minutes after the loss of membrane potential. Histologic outcomes were evaluated 5 days later. Results: Extracellular glutamate concentration in the low-flow group was significantly lower than that in the severe-low-flow group. Moreover, increases in extracellular glutamate concentration exhibited a linear relationship with decreases in CBF after the loss of membrane potential in the severe-low-flow group, and the percentage of damaged neurons exhibited a dose-response relationship with the extracellular glutamate concentration. The extracellular glutamate concentration required to cause 50% neuronal damage was estimated to be 387 μmol/L, at 8.7% of preischemia CBF. Regression analyses revealed that extracellular glutamate concentration increased by 21 μmol/L with each 1% decrease in residual CBF and that the percentage of damaged neurons increased by 2.6%. Conclusion: Our results indicate that residual CBF is an important factor that determines the extracellular glutamate concentration after the loss of membrane potential, and residual CBF would be one of the important determinants of neuronal cell prognosis.

Original languageEnglish
JournalJournal of Neurosurgical Anesthesiology
Publication statusAccepted/In press - Jan 1 2019



  • brain ischemia
  • cardiopulmonary resuscitation
  • cerebral blood flow
  • glutamate
  • resuscitation

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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