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Evaluation of Progesterone Receptor Antagonist and Maxi-K Channel Agonist as Neuroprotective in Feeney's Weight Drop Model of TBI
journal contribution
posted on 2023-02-14, 04:15 authored by MP Kumar, R Rajput, A Ralta, LJ Quintans-Júnior, SJ C Gutierrez, JM Barbosa-Filho, D Shekhawat, BD Radotra, Sunil GuptaSunil Gupta, B MedhiBackground: 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.
History
Journal
Neurology IndiaVolume
70Pagination
1601-1609Location
IndiaPublisher DOI
ISSN
0028-3886eISSN
1998-4022Language
enPublication classification
C1.1 Refereed article in a scholarly journalIssue
4Publisher
MedknowUsage metrics
Keywords
Anti-progesteroneMaxi-K channelcraniotomyneuroprotectiveprogesteronetraumatic brain injuryweight drop apparatusAnimalsBrain InjuriesBrain Injuries, TraumaticCarrier ProteinsDisease Models, AnimalLarge-Conductance Calcium-Activated Potassium ChannelsMaleNeuroprotectionNeuroprotective AgentsProto-Oncogene Proteins c-bcl-2RatsRats, Sprague-DawleyRats, WistarReceptors, Progesteronebcl-2-Associated X ProteinInjury (total) Accidents/Adverse EffectsInjury - Traumatic brain injuryInjury - Trauma - (Head and Spine)NeurosciencesBrain DisordersCognitive SciencesClinical Sciences not elsewhere classifiedNeurosciences not elsewhere classified
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