Evaluation of Progesterone Receptor Antagonist and Maxi-K Channel Agonist as Neuroprotective in Feeney's Weight Drop Model of TBI.

Autor:	Kumar MP; Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Rajput R; Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Ralta A; Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Quintans-Júnior LJ; Department of Physiology, Federal University of Sergipe, Sergipe, Brazil., C Gutierrez SJ; Ph.D., Coordination of Pharmacy-Federal University of Piaui, Teresina, Piaui, Brazil., Barbosa-Filho JM; Department of Pharmaceutical Sciences, Federal University of Paraíba, Brazil., Shekhawat D; Department of Anatomy, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Radotra BD; Department of Histopathology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Gupta SK; Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India., Medhi B; Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Jazyk:	angličtina
Zdroj:	Neurology India [Neurol India] 2022 Jul-Aug; Vol. 70 (4), pp. 1601-1609.
DOI:	10.4103/0028-3886.355164
Abstrakt:	Background: Neuroprotection in traumatic brain injury (TBI) is an unmet medical need. Objective: We evaluated two agents, aglepristone (progesterone receptor antagonist) and N-salicyloyltryptamine (STP) (activator of Maxi-K channel in GH3 cells), for neuroprotection in Feeney's weight drop model of TBI. Material and Methods: Forty-eight male Wistar rats were divided into six groups (n = 8 per group). A battery of six neurobehavioral tests was evaluated at the end of the first week (EO1W), second week (EO2W), and third week (EO3W). In addition, histopathological and immunohistochemistry (BAX, Bcl-2, and M30 Cytodeath) tests were performed at EO3W. Results: Aglepristone at 10 mg/kg showed significant neuroprotection compared to control as assessed by Rota-rod test at EO1W, VEFP right paw and 28-point neurobehavioral test at EO2W, MWM test at EO3W, and positive histopathological and IHC findings. Aglepristone at 20 mg/kg showed negative results as assessed by BAX expression, downregulation of Bcl-2, and positive M30 Cytodeath, thereby suggesting toxicity at higher doses. STP 100 mg/kg showed modest neuroprotective activity but failed to show a dose-response relationship at a dose of 50 mg/kg. Conclusion: The study shows that progesterone receptor antagonists have neuroprotection at lower doses and toxicity at higher doses. Competing Interests: None
Databáze:	MEDLINE
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