Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Wenjun Li; Renqi Huang; Ritu A. Shetty; Nopporn Thangthaeng; Ran Liu; Zhenglan Chen; Nathalie Sumien; Margaret Rutledge; Glenn H. Dillon; Fang Yuan; Michael J. Forster; James W. Simpkins; Shao-Hua Yang

Neurobiology of Disease (Nov 2013)

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model

Wenjun Li,
Renqi Huang,
Ritu A. Shetty,
Nopporn Thangthaeng,
Ran Liu,
Zhenglan Chen,
Nathalie Sumien,
Margaret Rutledge,
Glenn H. Dillon,
Fang Yuan,
Michael J. Forster,
James W. Simpkins,
Shao-Hua Yang

Affiliations

Wenjun Li: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Renqi Huang: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Ritu A. Shetty: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Nopporn Thangthaeng: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Ran Liu: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Zhenglan Chen: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Nathalie Sumien: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Margaret Rutledge: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
Glenn H. Dillon: Department of Physiology and Pharmacology, Center for Neuroscience, Health Science Center, West Virginia University, Medical Center Drive, Morgantown, WV 26506, USA
Fang Yuan: Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China
Michael J. Forster: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
James W. Simpkins: Department of Physiology and Pharmacology, Center for Neuroscience, Health Science Center, West Virginia University, Medical Center Drive, Morgantown, WV 26506, USA
Shao-Hua Yang: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; Beijing Neurosurgical Institute, Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Corresponding author at: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2699, USA. Fax: +1 817 735 2091.

Journal volume & issue: Vol. 59
pp. 18 – 25

Abstract

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Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague–Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30 days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30 days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30 days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both hippocampi was reduced at 30 days after stroke. This LTP impairment was prevented by blocking GABAA receptors. In addition, ERK activity was significantly reduced in both hippocampi. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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Abstract

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