Abstract | OBJECTIVES: DESIGN: Experimental animal study. SETTING: Research laboratory. SUBJECTS: Adult male mice and hippocampal brain slices. INTERVENTIONS: Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ- aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM). MEASUREMENTS AND MAIN RESULTS: CONCLUSIONS: Pharmacologic inhibition of α5 subunit-containing γ- aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ- aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.
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Authors | Shahin Khodaei, Sinziana Avramescu, Dian-Shi Wang, Heping Sheng, Nathan K Chan, Irene Lecker, Alejandro Fernandez-Escobar, Gang Lei, Michael B Dewar, Paul D Whissell, Andrew J Baker, Beverley A Orser |
Journal | Critical care medicine
(Crit Care Med)
Vol. 48
Issue 4
Pg. 533-544
(04 2020)
ISSN: 1530-0293 [Electronic] United States |
PMID | 32205600
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Imidazoles
- L 655,708
- Receptors, GABA-A
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Topics |
- Animals
- Behavior, Animal
(drug effects)
- Brain Injuries, Traumatic
(drug therapy)
- Cognition
(drug effects)
- Conditioning, Classical
(drug effects)
- Dose-Response Relationship, Drug
- Hippocampus
(drug effects)
- Imidazoles
(pharmacology)
- Long-Term Potentiation
(drug effects)
- Male
- Memory
(drug effects)
- Memory, Short-Term
(drug effects)
- Mice
- Models, Animal
- Receptors, GABA-A
(drug effects)
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