RT Journal Article T1 The cannabinoid agonist WIN55212 reduces brain damage in an in vivo model of hypoxic-ischemic encephalopathy in newborn A1 Fernandez-Lopez, David A1 Pazos, M. Ruth A1 Tolón, Rosa M. A1 Romero, Julián A1 Martínez Orgado, José Antonio A1 Moro Sánchez, María Ángeles A1 Lizasoaín Hernández, Ignacio AB Neonatal hypoxic-ischemic encephalopathy (NHIE) is a devastating condition for which effective therapeutic treatments are still unavailable. Cannabinoids emerge as neuroprotective substances in adult animal studies; therefore, we aimed herein to test whether cannabinoids might reduce brain damage induced by hypoxiaischemia (HI) in newborn rats. Thus, 7-d-old Wistar rats (P7) were exposed to 8% O2 for 120 min after left carotid artery ligature, then received s.c. vehicle (VEH) (HI+VEH), the cannabinoid agonist WIN55212 (WIN) (0.1 mg/kg), or WIN with the CB1 or CB2 receptor antagonist SR141617 (SR1) (3 mg/kg) or SR141588 (SR2) (2 mg/kg). Brain damage was assessed by magnetic resonance imaging (MRI) at 1, 3, and 7 d after the insult. At the end of the experiment, MRI findings were corroborated by histology (Nissl staining). HI+VEH showed an area of cytotoxic and vasogenic edema at 24 h after the insult, then evolving to necrosis. HI+WIN showed a similar damaged area at 24 h after the insult, but the final necrotic area was reduced by 66%. Coadministration of either SR1 or SR2 reversed the effects of WIN. In conclusion, likely by activating CB1 and CB2 receptors, WIN afforded robust neuroprotection in newborn rats after HI. PB Nature YR 2007 FD 2007 LK https://hdl.handle.net/20.500.14352/117009 UL https://hdl.handle.net/20.500.14352/117009 LA eng NO Fernández-López D, Pazos MR, Tolón RM, Moro MA, Romero J, Lizasoain I, Martínez-Orgado J. The cannabinoid agonist WIN55212 reduces brain damage in an in vivo model of hypoxic-ischemic encephalopathy in newborn rats. Pediatr Res. 2007 Sep;62(3):255-60. doi: 10.1203/PDR.0b013e318123fbb8. PMID: 17622949. DS Docta Complutense RD 22 abr 2025