The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury


“The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases. This overview, therefore, gives a current description of the main components of the EC system (including cannabinoid receptors, ligands, and related enzymes), to later analyze the EC system as a target for neonatal neuroprotection with a special focus on its neurogenic potential after hypoxic-ischemic brain injury.”

“The ubiquitous lipid signaling-based EC system is involved in outstanding regulatory functions throughout the human body, including neural development under physiological conditions and neuroprotection, and repair after pathophysiological processes.In the context of neonatal brain injury, the administration of endogenous or exogenous CBs, or the blockage of EC degradation, has revealed a strong neuroprotective response in different preclinical models after HI. Similarly, the possibility of tissue repair in the developing brain by enhancing the proliferative potential of the SVZ and SGZ neurogenic niches is currently under active investigation. Selective modulation of the EC system in the sites of damage by targeting the enzymes responsible for EC degradation may represent an important therapeutic approach in order to avoid non-desired widespread effects.Despite the clinical use of CB-related drugs that must be taken with caution, the modulation of the EC system to ameliorate the neurological consequences after neonatal HI is currently an exciting field of research with enormous possibilities for clinical translation.”

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