Title:Na+/HCO3− Co-transporters Inhibitor S0859 Attenuates Global Cerebral
Ischemia-reperfusion Injury of the CA1 Neurons in the Gerbil’s Hippocampus
Volume: 22
Issue: 7
Author(s): Meng Jia, Qian Zhang, Xi Guo, Ru Liu, Sha Liu, Nanyu Chen, Yunfu Wang, Qun Wang, Jianping Wu*Susan L. Campbell
Affiliation:
- Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for
Neurological Diseases, Beijing, China
- Advanced Innovation Center for Human Brain Protection, Capital Medical
University, Beijing, China
- School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology,
Wuhan, China
Keywords:
Cerebral I/R, Na+/HCO3 − co-transporter, delayed neuronal death, S0859, hippocampus, whole-cell patch clamp.
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.
