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Article

Celecoxib in a Preclinical Model of Repetitive Mild Traumatic Brain Injury: Hippocampal Learning Deficits Persist with Inflammatory and Excitotoxic Neuroprotection

School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton 4701, Australia
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Received: 9 February 2021 / Revised: 1 March 2021 / Accepted: 12 March 2021 / Published: 26 March 2021
Repetitive mild traumatic brain injuries (mTBIs) contribute to inflammation-induced neurodegeneration. Cycloxygenase (COX) enzymes produce inflammatory cytokines that influence the microglia response to neurotrauma. Celecoxib is a selective COX-2 inhibitor that is prescribed in some conditions of mTBI to alleviate symptoms of concussion, and has shown benefits in neurodegenerative conditions. We investigated molecular pathways of neuroinflammation in response to celecoxib treatment in a mouse model of repetetive mTBI. Fifteen mTBIs were delivered over 23 days in adult male C57BL/6J mice in one of four groups (control, celecoxib without impact, celecoxib with impact, and vehicle with impact). Cognitive function was assessed at 48 h and three months following the final mTBI. Morris Water Maze testing revealed impaired hippocampal spatial learning performance in the celecoxib treatment with the impact group compared to the vehicle with impact control in the acute phase, with celecoxib treatment providing no improvement compared with the control at chronic testing; mRNA analysis of the cerebral cortex and hippocampus revealed expression change, indicating significant improvement in microglial activation, inflammation, excitotoxicity, and neurodegeneration at chronic measurement. These data suggest that, in the acute phase following injury, celecoxib protected against neuroinflammation, but exacerbated clinical cognitive disturbance. Moreover, while there was evidence of neuroprotective alleviation of mTBI pathophysiology at chronic measurement, there remained no change in clinical features. View Full-Text
Keywords: concussion; animal models; neurobehavioral; rehabilitation concussion; animal models; neurobehavioral; rehabilitation
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MDPI and ACS Style

Hiskens, M.; Vella, R.; Schneiders, A.; Fenning, A. Celecoxib in a Preclinical Model of Repetitive Mild Traumatic Brain Injury: Hippocampal Learning Deficits Persist with Inflammatory and Excitotoxic Neuroprotection. Trauma Care 2021, 1, 23-37. https://0-doi-org.brum.beds.ac.uk/10.3390/traumacare1010003

AMA Style

Hiskens M, Vella R, Schneiders A, Fenning A. Celecoxib in a Preclinical Model of Repetitive Mild Traumatic Brain Injury: Hippocampal Learning Deficits Persist with Inflammatory and Excitotoxic Neuroprotection. Trauma Care. 2021; 1(1):23-37. https://0-doi-org.brum.beds.ac.uk/10.3390/traumacare1010003

Chicago/Turabian Style

Hiskens, Matthew, Rebecca Vella, Anthony Schneiders, and Andrew Fenning. 2021. "Celecoxib in a Preclinical Model of Repetitive Mild Traumatic Brain Injury: Hippocampal Learning Deficits Persist with Inflammatory and Excitotoxic Neuroprotection" Trauma Care 1, no. 1: 23-37. https://0-doi-org.brum.beds.ac.uk/10.3390/traumacare1010003

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