TY - JOUR
T1 - 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
AU - Kawase, Hirokazu
AU - Takeda, Yoshimasa
AU - Mizoue, Ryoichi
AU - Sato, Sachiko
AU - Fushimi, Miki
AU - Murai, Satoshi
AU - Morimatsu, Hiroshi
N1 - Funding Information:
Received for publication May 23, 2019; accepted October 26, 2019. From the Departments of *Anesthesiology; ‡Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; and †Department of Anesthesiology, Okayama University Medical School, Okayama, Japan. Supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (19K09351). This work has been presented at Resuscitation Science Symposium, American Heart Association, November 12-16, 2016, New Orleans, LA. The authors have no conflicts of interest to disclose. Address correspondence to: Yoshimasa Takeda, MD, PhD. E-mail: yoshit@cc.okayama-u.ac.jp. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website, www.jnsa. com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/ANA.0000000000000666
Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - brain ischemia
KW - cardiopulmonary resuscitation
KW - cerebral blood flow
KW - glutamate
KW - resuscitation
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U2 - 10.1097/ANA.0000000000000666
DO - 10.1097/ANA.0000000000000666
M3 - Article
C2 - 31834249
AN - SCOPUS:85076423444
SN - 0898-4921
VL - 33
SP - 356
EP - 362
JO - Journal of Neurosurgical Anesthesiology
JF - Journal of Neurosurgical Anesthesiology
IS - 4
ER -