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Published Online: 10 May 2013

Repeated Mild Closed Head Injury Impairs Short-Term Visuospatial Memory and Complex Learning

Publication: Journal of Neurotrauma
Volume 30, Issue Number 9

Abstract

Concussive force can cause neurocognitive and neurobehavioral dysfunction by inducing functional, electrophysiological, and/or ultrastructural changes within the brain. Although concussion-triggered symptoms typically subside within days to weeks in most people, in 15%–20% of the cases, symptomology can continue beyond this time point. Problems with memory, attention, processing speed, and cognitive flexibility (e.g., problem solving, conflict resolution) are some of the prominent post-concussive cognitive symptoms. Repeated concussions (with loss or altered consciousness), which are common to many contact sports, can exacerbate these symptoms. The pathophysiology of repeated concussions is not well understood, nor is an effective treatment available. In order to facilitate drug discovery to treat post-concussive symptoms (PCSs), there is a need to determine if animal models of repeated mild closed head injury (mCHI) can mimic the neurocognitive and histopathological consequences of repeated concussions. To this end, we employed a controlled cortical impact (CCI) device to deliver a mCHI directly to the skull of mice daily for 4 days, and examined the ensuing neurological and neurocognitive functions using beam balance, foot-fault, an abbreviated Morris water maze test, context discrimination, and active place avoidance tasks. Repeated mCHI exacerbated vestibulomotor, motor, short-term memory and conflict learning impairments as compared to a single mCHI. Learning and memory impairments were still observed in repeated mCHI mice when tested 3 months post-injury. Repeated mCHI also reduced cerebral perfusion, prolonged the inflammatory response, and in some animals, caused hippocampal neuronal loss. Our results show that repeated mCHI can reproduce some of the deficits seen after repeated concussions in humans and may be suitable for drug discovery studies and translational research.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 30Issue Number 9May 1, 2013
Pages: 716 - 726
PubMed: 23489238

History

Published online: 10 May 2013
Published in print: May 1, 2013
Published ahead of production: 14 March 2013

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Michael J. Hylin
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Sara A. Orsi
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Natalia S. Rozas
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Julia L. Hill
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Jing Zhao
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
John B. Redell
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Anthony N. Moore
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
Pramod K. Dash
Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, Texas.
The Vivian L. Smith Department of Neurosurgery, The University of Texas Medical School at Houston, Houston, Texas.

Notes

Address correspondence to:Pramod K. Dash, Ph.D.Department of Neurobiology and AnatomyThe University of Texas Medical School at HoustonPO Box 20708Houston, TX 77225E-mail: [email protected]

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