Research Article: Effect of Clemastine on Neurophysiological Outcomes in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy
Abstract:
Originally approved by the U.S. Food and Drug Administration (FDA) for its antihistamine properties, clemastine can also promote white matter integrity and has shown promise in the treatment of demyelinating diseases such as multiple sclerosis. Here, we conducted an in-depth analysis of the feasibility, safety, and neuroprotective efficacy of clemastine administration in near-term lambs (n = 25, 141–143 days) following a global ischemic insult induced via an umbilical cord occlusion (UCO) model. Lambs were randomly assigned to receive clemastine or placebo postnatally, and outcomes were assessed over a six-day period. Clemastine administration was well tolerated. While treated lambs demonstrated improvements in inflammatory scores, their neurodevelopmental outcomes were unchanged.
Introduction:
Clemastine is an FDA-approved antihistamine that also exhibits anti-muscarinic activity. Via H1-receptor (H1R) antagonism, clemastine impacts mast cell function to limit allergic responses [1]. Following brain ischemia, mast cells proliferate at the injury site, and their number rapidly and persistently increases for days and weeks, contributing to inflammation [2]. Interestingly, the H1-receptor is also expressed in the hypothalamus, hippocampus, brainstem, thalamus, and cortex of the central nervous system…
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