Background and Purpose—The endocannabinoid system has been involved in the modulation of neural stem cells
proliferation, survival and differentiation as well as in the generation of new oligodendrocyte progenitors in the postnatal
brain. The present work aims to test the effect of the synthetic Type 1 and Type 2 cannabinoid receptor agonist
WIN55212-2 on these processes in the context of neonatal rat brain hypoxia–ischemia (HI).
Methods—P7 Wistar rats were subjected to HI and treated either with WIN55212-2 (1 mg/kg) or vehicle twice daily for
7 days after HI and euthanized at 1, 2, 7, 14, or 28 days to explore white matter injury progression and the neurogenic
response in the subventricular zone after HI.
Results—Our findings reveal that WIN55212-2 promotes remyelination of the injured external capsule, increasing the
number of NG2 early oligodendrocyte progenitors 7 days after HI in this area and the number of APC mature
oligodendrocytes in the injured striatum 14 and 28 days after HI. WIN55212-2 also increases cell proliferation and
protein expression of the neuroblast marker doublecortin in the subventricular zone 7 days after neonatal HI as well as
the number of newly generated neuroblasts (5-bromodeoxyuridine/doublecortin cells) in the ipsilateral striatum 14
days after HI.
Conclusions—Our results suggest that the activation of the endocannabinoid system promotes white and gray matter
recovery after neonatal HI injury.