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

Kumar-M, Praveen; Rajput, Rohit; Ralta, Arti; Quintans-Júnior, Lucindo J.; Gutierrez, Stanley J. C.; Barbosa-Filho, Jose Maria; Shekhawat, Devendra; Radotra, B. D.; Gupta, S. K.; Medhi, Bikash; Kumar, M Praveen; C Gutierrez, Stanley J

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.

PROTEIN metabolism; BIOLOGICAL models; ANIMAL experimentation; CELL receptors; RATS; NEUROPROTECTIVE agents; BRAIN injuries; MEMBRANE proteins; MOLECULAR structure; ANIMALS; CARRIER proteins; PHARMACODYNAMICS

Neurology India, 2022, Vol 70, Issue 4, p1601

0028-3886

Academic Journal

10.4103/0028-3886.355164