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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Research Article

Na+/HCO3− Co-transporters Inhibitor S0859 Attenuates Global Cerebral Ischemia-reperfusion Injury of the CA1 Neurons in the Gerbil’s Hippocampus

Author(s): Meng Jia, Qian Zhang, Xi Guo, Ru Liu, Sha Liu, Nanyu Chen, Yunfu Wang, Qun Wang, Jianping Wu* and Susan L. Campbell

Volume 22, Issue 7, 2023

Published on: 22 July, 2022

Page: [1109 - 1119] Pages: 11

DOI: 10.2174/1871527321666220517121135

open access plus

Abstract

Background: Metabolic acidosis plays a key role in transient global cerebral ischemiareperfusion (I/R) induced delayed neuronal death (DND) of the hippocampal CA1 region of gerbils. Na+ coupled HCO3 - transporters (NBCs) mediated Na+/HCO3− - co-transportation can be activated by the pH gradient of intracellular and extracellular environments induced by acidosis. However, whether NBCs are activated and involved in I/R-induced neuronal injury is unknown.

Objective: In this work, we studied neuronal apoptosis, astrocyte activation, and hippocampusdependent memory task using a well-established transient global cerebral I/R model of gerbils and investigated whether the specific NBCs inhibitor S0859 could reverse this injury.

Methods: To explore the role of S0859 in I/R-induced DND, we established a transient global cerebral I/R model of Mongolian gerbils and studied neuronal apoptosis by using Nissl stain and TUNEL assay. The excitability and NBCs current were analyzed by whole-cell patch-clamp, while the cognitive function was evaluated by Barnes maze.

Results: We found that I/R increased the NBCs current, inhibited the excitability of CA1 neurons, and led to apoptosis in CA1 neurons. Selective NBCs inhibitor S0859 protected CA1 neurons from I/R induced neuronal cell death, astrocyte accumulation, and spatial memory impairment.

Conclusion: These findings indicate that NBCs mediate transient global cerebral I/R induced DND of CA1 neurons, and NBCs inhibitors could be a promising target to protect neuronal functions after I/R.

Keywords: Cerebral I/R, Na+/HCO3 − co-transporter, delayed neuronal death, S0859, hippocampus, whole-cell patch clamp.

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