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

Autor: Okigbo AA; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Helkowski MS; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Royes BJ; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Bleimeister IH; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Lam TR; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Bao GC; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Cheng JP; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Bondi CO; Physical Medicine & Rehabilitation, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Safar Center for Resuscitation Research, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Neurobiology, University of Pittsburgh, Pittsburgh, PA, 15213, United States; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15213, United States., Kline AE; 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: klineae@upmc.edu.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2019 Feb 16; Vol. 694, pp. 69-73. Date of Electronic Publication: 2018 Nov 22.
DOI: 10.1016/j.neulet.2018.11.030
Abstrakt: 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.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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