Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxicischemic brain injury

Abstract One of the most important causes of brain injury in the neonatal period is a perinatal hypoxicischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death. Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes. Among them, the endocannabinoid system emerges as a natural system of neuroprotection. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury. Research Highlights (1) A perinatal hypoxic-ischemic event is one of the most important causes of brain injury in the neonatal period. (2) Hypoxia/ischemia leads to brain cell damage, finally resulting in brain cell death. (3) The complex molecular mechanisms underlying hypoxic-ischemic brain injury cause unsatisfactory efficacy of treatments for this condition. (4) A thorough understanding of the mechanisms underlying hypoxic-ischemic brain injury will provide new insights for the development of novel neuroprotective agents for this condition. (5) The endocannabinoid system, which is naturally neuroprotective, is likely to play an important role in the prevention and treatment of hypoxic-ischemic brain injury.