Dose-dependent neurorestorative effects of amantadine after cortical impact injury.

Neurosci Lett

Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Psychology, University of Pittsburgh, Pittsburgh, PA, 15213, United States. Electronic address:

Published: February 2019

AI Article Synopsis

  • The study investigates the effectiveness of different doses of amantadine (AMT) for treating motor and cognitive impairment after traumatic brain injury (TBI).
  • Findings suggest that a dosage of 20 mg/kg of AMT significantly improved beam-balance recovery and spatial learning compared to controls, while other doses were not effective.
  • The research emphasizes the importance of optimizing drug dosing in clinical trials to accurately assess potential benefits following TBI.

Article Abstract

Numerous pharmacotherapies have been evaluated after experimental traumatic brain injury (TBI). While amantadine (AMT) has shown potential for clinical efficacy, the few studies on its effectiveness have been mixed. It is possible that suboptimal dosing, due to the evaluation of only one dose, may be causing the discrepancies in outcomes. Hence, the goal of the current study was to conduct a dose response of AMT after TBI to determine an optimal behavioral benefit. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to receive once daily intraperitoneally injections of AMT (10, 20, or 40 mg/kg) or saline vehicle (VEH, 1 mL/kg) commencing 24 h after injury for 19 days. Motor and cognitive function were assessed on post-operative days 1-5 and 14-19, respectively. There were no statistical differences among the sham groups treated with AMT or VEH so the data were pooled. AMT (20 mg/kg) facilitated beam-balance recovery and spatial learning relative to VEH-treated controls (p < 0.05). No other doses of AMT were effective. These results indicate that dosing should be carefully considered when assessing the effects of pharmacotherapies after TBI so that potential benefits are not inadvertently missed.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6369006PMC
http://dx.doi.org/10.1016/j.neulet.2018.11.030DOI Listing

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