1. Evaluation of Progesterone Receptor Antagonist and Maxi-K Channel Agonist as Neuroprotective in Feeney's Weight Drop Model of TBI.
- Author
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Kumar MP, Rajput R, Ralta A, Quintans-Júnior LJ, C Gutierrez SJ, Barbosa-Filho JM, Shekhawat D, Radotra BD, Gupta SK, and Medhi B
- Subjects
- Animals, Carrier Proteins, Disease Models, Animal, Male, Neuroprotection drug effects, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Rats, Sprague-Dawley, Rats, Wistar, bcl-2-Associated X Protein metabolism, Brain Injuries pathology, Brain Injuries, Traumatic drug therapy, Large-Conductance Calcium-Activated Potassium Channels agonists, Neuroprotective Agents pharmacology, Neuroprotective Agents therapeutic use, Receptors, Progesterone antagonists & inhibitors
- Abstract
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
- Published
- 2022
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