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.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Animals, Newborn
  • Benzoxazines / pharmacology*
  • Brain* / anatomy & histology
  • Brain* / drug effects
  • Brain* / pathology
  • Cannabinoids / agonists*
  • Cannabinoids / metabolism
  • Hypoxia-Ischemia, Brain / pathology*
  • Magnetic Resonance Imaging
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Wistar

Substances

  • Analgesics
  • Benzoxazines
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Neuroprotective Agents
  • Win 55212-2