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Sedative And Neurotoxic Properties Of Brexanolone Compared To Midazolam In The Developing Rodent Brain, Jacob Huffman

Dissertations

The developing brain is susceptible to extensive neurotoxicity following exposure to sedative/anesthetic drugs (SADs). Every year hundreds of thousands of children around the world are exposed to SADs with no viable non-neurotoxic agents approved for clinical use. Allopregnanolone (AlloP) has well-established sedative effects in adults and neonates. AlloP and many SADs produce sedation/anesthesia through allosteric modulation of GABA_A receptors, which is one of two principal mechanisms behind SAD-induced neurotoxicity. Evidence suggests AlloP has the unique capacity to regulate key apoptotic factors in adults and is widely involved with critical stages of neurodevelopment, indicating this neurosteroid might serve as a …