Protective effects of remote ischemic preconditioning against spinal cord ischemia-reperfusion injury in rats

Akira Mukai; Koichi Suehiro; Aya Kimura; Yohei Fujimoto; Tomoharu Funao; Takashi Mori; Kiyonobu Nishikawa

doi:10.1016/j.jtcvs.2020.03.094

Protective effects of remote ischemic preconditioning against spinal cord ischemia-reperfusion injury in rats

J Thorac Cardiovasc Surg. 2022 Feb;163(2):e137-e156. doi: 10.1016/j.jtcvs.2020.03.094. Epub 2020 Apr 11.

Authors

Akira Mukai¹, Koichi Suehiro², Aya Kimura¹, Yohei Fujimoto¹, Tomoharu Funao¹, Takashi Mori¹, Kiyonobu Nishikawa¹

Affiliations

¹ Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
² Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka, Japan. Electronic address: suehirokoichi@yahoo.co.jp.

PMID: 32414598
DOI: 10.1016/j.jtcvs.2020.03.094

Abstract

Objectives: We aimed to investigate the protective effect of remote ischemic preconditioning against spinal cord ischemia and find a clue to its mechanism by measuring glutamate concentrations in the spinal ventral horn.

Methods: Male Sprague-Dawley rats were divided into 5 groups (n = 6 in each group) as follows: sham; SCI (only spinal cord ischemia); RIPC/SCI (perform remote ischemic preconditioning before spinal cord ischemia); MK-801/RIPC/SCI (administer MK-801, N-methyl-D-aspartate receptor antagonist, before remote ischemic preconditioning); and MK-801/SCI (administer MK-801 without remote ischemic preconditioning). Remote ischemic preconditioning was achieved by brief limb ischemia 80 minutes before spinal cord ischemia. MK-801 (1 mg/kg, intravenous) was administered 60 minutes before remote ischemic preconditioning. The glutamate concentration in the ventral horn was measured by microdialysis for 130 minutes after spinal cord ischemia. Immunofluorescence was also performed to evaluate the expression of N-methyl-D-aspartate receptor 2B subunit in the ventral horn 130 minutes after spinal cord ischemia.

Results: The glutamate concentrations in the spinal cord ischemia group were significantly higher than in the sham group at all time points (P < .01). Remote ischemic preconditioning attenuated the spinal cord ischemia-induced glutamate increase. When MK-801 was preadministered before remote ischemic preconditioning, glutamate concentration was increased after spinal cord ischemia (P < .01). Immunofluorescence showed that remote ischemic preconditioning prevented the increase in the expression of N-methyl-D-aspartate receptor 2B subunit on the surface of motor neurons (P = .047).

Conclusions: Our results showed that remote ischemic preconditioning prevented spinal cord ischemia-induced extracellular glutamate increase in ventral horn and suppressed N-methyl-D-aspartate receptor 2B subunit expression.

Keywords: N-methyl-D-aspartate receptor; glutamate; microdialysis; remote ischemic preconditioning; spinal cord ischemia.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anterior Horn Cells / metabolism
Dizocilpine Maleate / pharmacology*
Glutamic Acid / analysis*
Ischemic Preconditioning / methods*
Neuroprotective Agents / pharmacology
Rats
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
Reperfusion Injury* / metabolism
Reperfusion Injury* / prevention & control
Spinal Cord / blood supply*
Spinal Cord Ischemia* / metabolism
Spinal Cord Ischemia* / prevention & control
Treatment Outcome

Substances

Neuroprotective Agents
Receptors, N-Methyl-D-Aspartate
Glutamic Acid
Dizocilpine Maleate