Effect of Clemastine on Neurophysiological Outcomes in an Ovine Model of Neonatal Hypoxic-Ischemic Encephalopathy

Author:

Mike Jana Krystofova1,White Yasmine1,Hutchings Rachel S.1ORCID,Vento Christian1,Ha Janica1,Iranmahboub Ariana1,Manzoor Hadiya1,Gunewardena Anya1ORCID,Cheah Cheryl1,Wang Aijun2ORCID,Goudy Brian D.3,Lakshminrusimha Satyan3ORCID,Long-Boyle Janel45,Fineman Jeffrey R.15ORCID,Ferriero Donna M.16,Maltepe Emin157

Affiliation:

1. Department of Pediatrics, University of California San Francisco, San Francisco, CA 94158, USA

2. Department of Biomedical Engineering, University of California Davis, Davis, CA 95817, USA

3. Department of Pediatrics, University of California Davis, Davis, CA 95817, USA

4. School of Pharmacy, University of California San Francisco, San Francisco, CA 94143, USA

5. Initiative for Pediatric Drug and Device Development, San Francisco, CA 94143, USA

6. Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94158, USA

7. Department of Biomedical Sciences, University of California San Francisco, San Francisco, CA 94143, USA

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.

Funder

Bill & Melinda Gates Foundation

Publisher

MDPI AG

Subject

Pediatrics, Perinatology and Child Health

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