Changes in arginase isoforms in a murine model of neonatal brain hypoxia-ischemia.

Abstract

Background:Arginases (ARG-isoforms, ARG-1/ARG-2) are key regulatory enzymes of inflammation and tissue repair, however their role after neonatal brain hypoxia (H) and hypoxia-ischemia (HI) remains unknown.Methods:C57BL/6-mice subjected to the Vannucci procedure on postnatal day 9 were sacrificed at different timepoints. The degree of brain damage was assessed histologically. ARG spatiotemporal localization was determined via immunohistochemistry. ARG expression was measured by Western blot and activity spectrophotometrically.Results:ARG-isoforms expression increased during neurodevelopment (P9-P17) in the cortex and hippocampus. This was suppressed with H and HI only in the hippocampus. In the cortex, both isoforms increased with H alone and only ARG-2 increased with HI at 3 d. ARG activity during neurodevelopment remained unchanged but increased at 1 d with H and not HI. ARG-1 localized with microglia at the injury site as early as 4 h after injury, while ARG-2 localized with neurons.Conclusions:ARG-isoforms expression increases with age from P9-P17 but is suppressed by injury specifically in the hippocampus and not in the cortex. Both, levels and activity of ARG-isoforms increase with H while ARG-1 immunolabelling is upregulated in the HI cortex. Evidently, ARG-isoforms in brain differ in spatiotemporal localization, expression and activity during neurodevelopment and after injury.