Amantadine Improves Cognitive Outcome and Increases Neuronal Survival after Fluid Percussion Traumatic Brain Injury in Rats
| Autor: | Jack Nguyen, Ken C. Van, Tao Wang, Gregory T. Went, Bruce G. Lyeth, Xian Jian Huang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cell Survival Traumatic brain injury Dopamine Agents CA2 Region Hippocampal Morris water navigation task Cell Count Reuptake Rats Sprague-Dawley Cognition Pharmacokinetics Memory Dopamine Amantadine medicine Animals Learning Maze Learning Neurons Analysis of Variance Dose-Response Relationship Drug Body Weight Glutamate receptor medicine.disease CA3 Region Hippocampal Rats Treatment Outcome Brain Injuries Anesthesia Neurology (clinical) Psychology medicine.drug Blood drawing |
| Zdroj: | Journal of Neurotrauma. 31:370-377 |
| ISSN: | 1557-9042 0897-7151 |
| Popis: | This study evaluated the effects of clinically relevant concentrations of amantadine (AMT) on cognitive outcome and hippocampal cell survival in adult rats after lateral fluid percussion traumatic brain injury (TBI). AMT is an antagonist of the N-methyl-D-aspartate-type glutamate receptor, increases dopamine release, blocks dopamine reuptake, and has an inhibitory effect on microglial activation and neuroinflammation. Currently, AMT is clinically used as an antiparkinsonian drug. Amantadine or saline control was administered intraperitoneally, starting at 1 h after TBI followed by dosing three times daily for 16 consecutive days at 15, 45, and 135 mg/kg/day. Terminal blood draws were obtained from TBI rats at the time of euthanasia at varying time points after the last amantadine dose. Pharmacokinetics analysis confirmed that the doses of AMT achieved serum concentrations similar to those observed in humans receiving therapeutic doses (100-400 mg/day). Acquisition of spatial learning and memory retention was assessed using the Morris water maze (MWM) on days 12-16 after TBI. Brain tissues were collected and stained with Cresyl-violet for long-term cell survival analysis. Treatment with 135mg/kg/day of AMT improved acquisition of learning and terminal cognitive performance on MWM. The 135-mg/kg/day dosing of AMT increased the numbers of surviving CA2-CA3 pyramidal neurons at day 16 post-TBI. Overall, the data showed that clinically relevant dosing schedules of AMT affords neuroprotection and significantly improves cognitive outcome after experimental TBI, suggesting that it has the potential to be developed as a novel treatment of human TBI. |
| Databáze: | OpenAIRE |
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