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Review
. 2023 Oct;20(6):1603-1615.
doi: 10.1007/s13311-023-01428-7. Epub 2023 Aug 31.

Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury

Todd A Verdoorn  1 , Tom J Parry  2 , Graziano Pinna  3 , Jonathan Lifshitz  4
Affiliations
Review

Neurosteroid Receptor Modulators for Treating Traumatic Brain Injury

Todd A Verdoorn et al. Neurotherapeutics. 2023 Oct.

Abstract

Traumatic brain injury (TBI) triggers wide-ranging pathology that impacts multiple biochemical and physiological systems, both inside and outside the brain. Functional recovery in patients is impeded by early onset brain edema, acute and chronic inflammation, delayed cell death, and neurovascular disruption. Drug treatments that target these deficits are under active development, but it seems likely that fully effective therapy may require interruption of the multiplicity of TBI-induced pathological processes either by a cocktail of drug treatments or a single pleiotropic drug. The complex and highly interconnected biochemical network embodied by the neurosteroid system offers multiple options for the research and development of pleiotropic drug treatments that may provide benefit for those who have suffered a TBI. This narrative review examines the neurosteroids and their signaling systems and proposes directions for their utility in the next stage of TBI drug research and development.

Keywords: Allopregnanolone; Drug therapy; Neurosteroid; Progesterone; Traumatic brain injury.

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Conflict of interest statement

This work received no direct funding from any of the author’s institutions or funders. We are aware of no conflicts of interest involving the content of this manuscript.

Figures

Fig. 1
Fig. 1
Biochemical network of neurosteroids and related molecules. Biosynthesis of neurosteroids. ACAT, acyl coenzyme A cholesterol acyltransferase; AROM, aromatase; CYP, cytochrome P450 hydroxylase; CYPscc, cytochrome P450 side-chain cleavage; HSD, hydroxysteroid oxidoreductase/dehydrogenase; nCEH, neutral cholesterol ester hydrolase; RED, reductase; SULT, sulfotransferase
See this image and copyright information in PMC

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