The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia

Brain damage after hypoxia-ischemia (HI) occurs in an age-dependent manner. Neuroprotective strategies assumed to be effective in adults might have deleterious effects in the immature brain. In order to create effective therapies, the complex pathophysiology of HI in the developing brain requires exploring new mechanisms. Critical determinants of neuronal survival after HI are the extent of vascular dysfunction, inflammation, and oxidative stress, followed later by tissue repair. The key enzyme of these processes in the human body is arginase (ARG) that acts via the bioavailability of nitric oxide, and the synthesis of polyamines and proline. ARG is expressed throughout the brain in different cells. However, little is known about the effect of ARG in pathophysiological states of the brain, especially hypoxia-ischemia. Here, we summarize the role of ARG during neurodevelopment as well as in various brain pathologies.