Acute administration of perampanel, an AMPA receptor antagonist, reduces cognitive impairments after traumatic brain injury in rats
| Autor: | Virginia Aida, Candace L. Floyd, Jerzy P. Szaflarski, Tracy L. Niedzielko |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Elevated plus maze Traumatic brain injury Pyridones bcl-X Protein Hippocampus Morris water navigation task AMPA receptor Pharmacology Neuroprotection Rats Sprague-Dawley 03 medical and health sciences Perampanel chemistry.chemical_compound 0302 clinical medicine Cognition Developmental Neuroscience Brain Injuries Traumatic Nitriles medicine Animals Cognitive Dysfunction Receptors AMPA Maze Learning Spatial Memory bcl-2-Associated X Protein business.industry Antagonist medicine.disease Rats Disease Models Animal 030104 developmental biology Neuroprotective Agents Treatment Outcome Neurology chemistry business Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery |
| Zdroj: | Experimental neurology. 327 |
| ISSN: | 1090-2430 |
| Popis: | Traumatic brain injury (TBI) is a major cause of death and physical as well as cognitive disability for which an effective treatment option remains to be identified. Evidence in preclinical models has indicated that antagonists of the α-amino-3-hydroxy-5-methyl-4-isozazole propionate (AMPA) receptor exert neuroprotective effects after mechanical injury in vitro and in vivo. In particular, 2-(2-oxo-1-phenyl-5-pyridin-2-yl-1,2-dihydropyridin-3-yl)benzonitrile hydrate (perampanel), a selective AMPA receptor antagonist with good bioavailability, was recently shown to therapeutically protect against the sequelae of TBI in the rodent controlled cortical impact model. However, this model induces a largely focal injury and is less representative of diffuse injury components that occur in TBI resulting from acceleration/deceleration forces. Here, we investigated the neuroprotective effects of perampanel in the rodent lateral fluid percussion injury model (LFPI), which produces both focal and diffuse injury. Pre- or post-injury administration of perampanel in male adult rats attenuated the injury-induced increase in the pro-apoptotic bax/bcl-xL ratio in the hippocampus; reduced impairments in learning and memory, assessed by the Morris water maze test; and reduced impairments in reward-seeking behavior, assessed by a female encounter test. Although additional studies are needed to determine the sex-related differences in the neuroprotective effects, these results provide support for the therapeutic potential of perampanel in TBI. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect