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Time and Brain Region-Dependent Excitatory Neurochemical Alterations in Bilateral Common Carotid Artery Occlusion Global Ischemia Model

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Abstract

Strict metabolic regulation in discrete brain regions leads to neurochemical changes in cerebral ischemia. Accumulation of extracellular glutamate is one of the early neurochemical changes that take place during cerebral ischemia. Understanding the sequential neurochemical processes involved in cerebral ischemia-mediated excitotoxicity before the clinical intervention of revascularization and reperfusion may greatly influence future therapeutic strategies for clinical stroke recovery. This study investigated the influence of time and brain regions on excitatory neurochemical indices in the bilateral common carotid artery occlusion (BCCAO) model of global ischemia. Male Wistar rats were subjected to BCCAO for 15 and 60 min to evaluate the effect of ischemia duration on excitatory neurochemical indices (dopamine level, glutamine synthetase, glutaminase, glutamate dehydrogenase, aspartate aminotransferase, monoamine oxidase, acetylcholinesterase, and Na+ K+ ATPase activities) in the discrete brain regions (cortex, striatum, cerebellum, and hippocampus). BCCAO without reperfusion caused marked time and brain region-dependent alterations in glutamatergic, glutaminergic, dopaminergic, monoaminergic, cholinergic, and electrogenic homeostasis. Prolonged BCCAO decreased cortical, striatal, and cerebellar glutamatergic, glutaminergic, dopaminergic, cholinergic, and electrogenic activities; increased hippocampal glutamatergic, glutaminergic, dopaminergic, and cholinergic activities, increased cortical and striatal monoaminergic activity; decreased cerebellar and hippocampal monoaminergic activity; and decreased hippocampal electrogenic activity. This suggests that excitatory neurotransmitters play a major role in the tissue-specific metabolic plasticity and reprogramming that takes place between the onset of cardiac arrest-mediated global ischemia and clinical intervention of recanalization. These tissue-specific neurochemical indices may serve as diagnostic and therapeutic strategies for mitigating the progression of ischemic damage before revascularization.

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Data Availability

Enquiries about data availability should be directed to the authors.

Abbreviations

BCCAO:

Bilateral common carotid artery occlusion

GS:

Glutamine synthetase activity

GA:

Glutaminase activity

GDH:

Glutamate dehydrogenase activity

AST:

Aspartate aminotransferase activity

DA:

Dopamine level

MAO:

Monoamine oxidase activity

AChE:

Acetylcholinesterase activity

NKA:

Na+ K+ ATPase activity

TCA:

Tricarboxylic acid

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Acknowledgements

We thank the Department of Biotechnology, Government of India (DBT), and The World Academy of Science (TWAS) for the award of the DBT-TWAS Sandwich Postgraduate Fellowship to OOB (FR Number: 3240306353).

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No specific grant from funding agencies in public, commercial, or non-profit organizations was received by this research.

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Authors and Affiliations

  1. Biochemical and Molecular Pharmacology and Toxicology Laboratories, Department of Biochemistry, School of Life Sciences, The Federal University of Technology, PMB 704, 340110, Akure, Nigeria

    Olubukola Benedicta Ojo, Zainab Abiola Amoo, Mary Tolulope Olaleye & Afolabi Clement Akinmoladun

  2. Sleep Research Laboratory, School of Life Sciences, Jawaharlal Nehru University, 110067, New Delhi, India

    Olubukola Benedicta Ojo & Sushil Kumar Jha

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  1. Olubukola Benedicta Ojo
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Contributions

OBO and ACA contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by OBO, ZAA, and ACA. Research supervision and data validation were performed by ACA, SKJ and MTO. The first draft of the manuscript was written by OBO and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Olubukola Benedicta Ojo or Afolabi Clement Akinmoladun.

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Ojo, O.B., Amoo, Z.A., Olaleye, M.T. et al. Time and Brain Region-Dependent Excitatory Neurochemical Alterations in Bilateral Common Carotid Artery Occlusion Global Ischemia Model. Neurochem Res 48, 96–116 (2023). https://doi.org/10.1007/s11064-022-03732-8

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