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Front. Pharmacol. | doi: 10.3389/fphar.2019.01131

CANNABIDIOL ADMINISTRATION PREVENTS HYPOXIA-ISCHEMIA-INDUCED HYPOMYELINATION IN NEWBORN RATS

 Maria Ceprian1, Carlos Vargas2, Laura García-Toscano1,  Federica Penna3, Laura Jiménez-Sánchez4,  Svein Achicallende5, Izaskun Elezgarai5, Pedro Grandes5, William Hind6,  M Ruth Pazos7 and  Jose Martínez-Orgado8*
  • 1Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, Spain
  • 2Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Spain
  • 3University of Insubria, Italy
  • 4Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana, Hospital Universitario Puerta de Hierro Majadahonda, Spain
  • 5Faculty of Medicine and Nursing, University of the Basque Country, Spain
  • 6GW Pharmaceuticals, United Kingdom
  • 7Hospital Universitario Fundación Alcorcón, Spain
  • 8San Carlos University Clinical Hospital, Spain

Neonatal hypoxia-ischemia (HI) is a risk factor for myelination disturbances, a key factor for cerebral palsy. Cannabidiol (CBD) protects neurons and glial cells after HI insult in newborn animals. We hereby aimed to study CBD’s effects on long-lasting HI-induced myelination deficits in newborn rats. Thus, P7 Wistar rats received s.c. vehicle (HV) or cannabidiol (HC) after HI brain damage (left carotid artery electrocoagulation plus 10% O2 for 112 min). Controls were non-HI pups. At P37 neurobehavioral tests were performed and immunohistochemistry (quantifying mature oligodendrocyte [mOL] populations and myelin basic protein [MBP] density) and electron microscopy (determining axon number, size and myelin thickness) studies were conducted in cortex (CX) and white matter (WM). Expression of BDNF (brain derived neurotrophic factor) and GDNF (glial derived neurotrophic factor) were analyzed by western blot at P14. HI reduced mOL or MBP in CX but not in WM. In both CX and WM axon density and myelin thickness were reduced. MBP impairment correlated with functional deficits. CBD administration resulted in normal function associated with normal mOL and MBP, as well as normal axon density and myelin thickness in all areas. CBD’s effects were not associated with increased BDNF or GDNF expression. In conclusion, HI injury in newborn rats resulted in long-lasting myelination disturbance, associated with functional impairment. CBD treatment preserved function and myelination, likely as a part of a general neuroprotective effect.

Keywords: Hypoxia-ischemia (HI), myelin alteration, Cannabidiol, Newborn, Rat - brain

Received: 01 Apr 2019; Accepted: 30 Aug 2019.

Copyright: © 2019 Ceprian, Vargas, García-Toscano, Penna, Jiménez-Sánchez, Achicallende, Elezgarai, Grandes, Hind, Pazos and Martínez-Orgado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jose Martínez-Orgado, San Carlos University Clinical Hospital, Madrid, Spain, jose.martinezo@salud.madrid.org