Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets.
To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia). Nonhypoxic-ischemic sham-operated piglets remained as controls. Brain damage was studied by near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) and by histologic assessment (Nissl and FluoroJadeB staining). In HI+vehicle, HI led to severe cerebral hemodynamic and metabolic impairment, as reflected in NIRS by an increase in total Hb index (THI) and a decrease in the fractional tissue oxygenation extraction (FTOE); in HI+CBD the increase of THI was blunted and FTOE remained similar to SHAM. HI profoundly decreased EEG amplitude, which was not recovered in HI+vehicle, indicating cerebral hypofunction; seizures were observed in all HI+vehicle. In HI+CBD, however, EEG amplitude recovered to 46.4 7.8% baseline and seizures appeared only in 4/8 piglets (both p < 0.05). The number of viable neurons decreased and that of degenerating neurons increased in HI+vehicle; CBD reduced both effects by more than 50%. CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects. In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits.
Alvarez
Francisco J
FJ
Laboratorio de Fisiopatología Perinatal Experimental, Gurutzetako Ospitalea, Bilbo, Bizkaia, Spain.
Lafuente
Hector
H
Rey-Santano
M Carmen
MC
Mielgo
Victoria E
VE
Gastiasoro
Elena
E
Rueda
Miguel
M
Pertwee
Roger G
RG
Castillo
Ana I
AI
Romero
Julián
J
Martínez-Orgado
José
J
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D002185:Cannabidiol / Q000494:pharmacology*; D004569:Electroencephalography; D006439:Hemodynamics / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013552:Swine
D018696:Neuroprotective Agents; D002185:Cannabidiol