Cannabidiol Administration Prevents Hypoxia-Ischemia-Induced Hypomyelination in Newborn Rats

Frontiers in Pharmacology

María Ceprián²  Federica Penna³  Laura Jiménez-Sánchez⁴  Carlos Vargas⁵  José Martínez-Orgado⁵  William Hind⁶  Laura García-Toscano⁷  M. Ruth Pazos⁸  Svein Achicallende⁹  Pedro Grandes⁹  Izaskun Elezgarai⁹ 

[1] CIBER de Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain;Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain;Department of DBSV, Laboratory of Neuropsychopharmacology, University of Insubria, Varese, Italy;Department of Experimental Medicine, Health Research Institute Puerta de Hierro Majadahonda, Madrid, Spain;Division of Neonatology, Hospital Clínico San Carlos - IdISSC, Madrid, Spain;GW Research Ltd, Cambridge, United Kingdom;Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain;Laboratorio de Apoyo a la Investigación, Hospital Universitario Fundación Alcorcón, Madrid, Spain;School of Medicine and Nursery, Universidad del País Vasco, Bilbao, Spain;

关键词: hypoxia-ischemia;    myelin;    cannabidiol;    newborn;    rat;   

DOI  :  10.3389/fphar.2019.01131

来源: DOAJ

【 摘 要 】

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 brain-derived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF) 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.

【 授权许可】

Unknown