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Evaluation of Progesterone Receptor Antagonist and Maxi-K Channel Agonist as Neuroprotective in Feeney's Weight Drop Model of TBI.
- Source :
- Neurology India; Jul/Aug2022, Vol. 70 Issue 4, p1601-1609, 18p
- Publication Year :
- 2022
-
Abstract
- <bold>Background: </bold>Neuroprotection in traumatic brain injury (TBI) is an unmet medical need.<bold>Objective: </bold>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.<bold>Material and Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>The study shows that progesterone receptor antagonists have neuroprotection at lower doses and toxicity at higher doses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00283886
- Volume :
- 70
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Neurology India
- Publication Type :
- Academic Journal
- Accession number :
- 159889976
- Full Text :
- https://doi.org/10.4103/0028-3886.355164