RT Journal Article
T1 Cannabidiol reduces brain damage and improves functional recovery in a neonatal rat model of arterial ischemic stroke
A1 Barata, Lorena
A1 Arruza Gómez, Luis
A1 Rodríguez, María José
A1 Aleo, Eshter
A1 Vierge, Eva
A1 Criado Vega, Enrique Alberto
A1 Ceprián Costoso, María
A1 Martínez Orgado, José Antonio
AB Objective: Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection.Methods: One day-old HI (carotid clamp and FiO2 10% for 20 min) piglets were randomized to vehicle or cannabidiol 1 mg/kg i.v. u.i.d. for three doses after being submitted to normothermia or 48 h-long hypothermia with a subsequent rewarming period of 6 h. Non-manipulated piglets (naïve) served as controls. Hemodynamic or respiratory parameters as well as brain activity (aEEG amplitude) were monitored throughout the experiment. Following termination, brains were obtained for histological (TUNEL staining, apoptosis; immunohistochemistry for Iba-1, microglia), biochemical (protein carbonylation, oxidative stress; and TNFα concentration, neuroinflammation) or proton magnetic resonance spectroscopy (Lac/NAA: metabolic derangement; Glu/NAA: excitotoxicity).Results: HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated.Conclusions: cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone.
PB Elsevier
SN 0028-3908
YR 2019
FD 2019-03-01
LK https://hdl.handle.net/20.500.14352/117237
UL https://hdl.handle.net/20.500.14352/117237
LA eng
NO Barata, L., Arruza, L., Rodríguez, M. J., Aleo, E., Vierge, E., Criado, E., Sobrino, E., Vargas, C., Ceprián, M., Gutiérrez-Rodríguez, A., Hind, W., & Martínez-Orgado, J. (2019). Neuroprotection by cannabidiol and hypothermia in a piglet model of newborn hypoxic-ischemic brain damage. Neuropharmacology, 146, 1–11. https://doi.org/10.1016/j.neuropharm.2018.11.020
NO R + D + I 2008–2011Plan for Scientific and Technical Research and Innovation 2013-2016Biomedicine Program
NO Instituto de Salud Carlos III
NO Unión Europea
NO Comunidad Autónoma de Madrid
NO GW Research Ltd
DS Docta Complutense
RD 18 abr 2025