Anti-apoptotic and Immunomodulatory Effect of CB2 Agonist, JWH133, in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy
In Summary
Hypoxic ischemic encephalopathy (HIE) is the brain damage caused by lack of blood flow, which delivers oxygen to the brain for an extended period of time. Neonatal HIE is associated with high risks of permanent disability or even death in infants. Therapeutic hypothermia is the current standard-of-care for newborns who have experienced oxygen deprivation leading to HIE. Unfortunately, not all Neonatal Intensive Care Units (NICUs) are equipped to provide therapeutic hypothermia and furthermore, over 40% of newborns receiving hypothermia still develop adverse neurological conditions. Therefore, current research is focused on developing alternative or adjuvant treatments to hypothermia for HIE.
One of the key cellular pathways leading to neuronal injuries in HIE is inflammation. The endocannabinoid system is a signalling pathway in the human body that has been shown to reduce inflammation-activating agents and decrease cellular responses to inflammation in adult mice with obstructed blood flow to the brain. More particularly, the cannabinoid receptor type 2 (CB2) is known to be highly expressed in immune cells in the central nervous system.
Most recently, scientists found evidence that in mice with brain oxygen deprivation, the expression of CB2 in neurons increases drastically - 2 fold after 8 hours and 5 fold after injury. Furthermore, activation of CB2, either alone or in combination with hyperthermia treatment, reduces inflammatory agents and therefore protects neurons against HIE-related damages. These findings suggested that pharmaceutical compounds that activate CB2 serve as potential alternative or adjuvant therapy to hypothermia in treatment of neonatal HIE.
One of the key cellular pathways leading to neuronal injuries in HIE is inflammation. The endocannabinoid system is a signalling pathway in the human body that has been shown to reduce inflammation-activating agents and decrease cellular responses to inflammation in adult mice with obstructed blood flow to the brain. More particularly, the cannabinoid receptor type 2 (CB2) is known to be highly expressed in immune cells in the central nervous system.
Most recently, scientists found evidence that in mice with brain oxygen deprivation, the expression of CB2 in neurons increases drastically - 2 fold after 8 hours and 5 fold after injury. Furthermore, activation of CB2, either alone or in combination with hyperthermia treatment, reduces inflammatory agents and therefore protects neurons against HIE-related damages. These findings suggested that pharmaceutical compounds that activate CB2 serve as potential alternative or adjuvant therapy to hypothermia in treatment of neonatal HIE.