Genetic deletion of CD36 enhances injury after acute neonatal stroke.

Abstract

The scavenger receptor CD36 is injurious in acute experimental focal stroke and neurodegenerative diseases in the adult. We investigated the effects of genetic deletion of CD36 (CD36ko) on acute injury, and oxidative and inflammatory signaling after neonatal stroke. Postnatal day 9 CD36ko and wild-type (WT) mice were subjected to a transient middle cerebral artery occlusion (MCAO). Injury, phagocytosis of dying cells, and CD36 inflammatory signaling were determined. While the volume of tissue at risk by diffusion-weighted magnetic resonance imaging during MCAO was similar in neonatal CD36ko and WT mice, by 24 hours after reperfusion, injury was more severe in CD36ko and was associated with increased caspase-3 cleavage and reduced engulfment of neurons expressing cleaved caspase-3 by activated microglia. No significant superoxide generation was observed in activated microglia in injured WT, whereas increased superoxide production in vessels and nuclear factor (NF)-κB activation induced by MCAO were unaffected by lack of CD36. Lyn expression was higher in injured CD36ko, and cell type-specific patterns of Lyn expression were altered; Lyn was expressed in endothelial cells and microglia in WT but predominantly in dying neurons in CD36ko. Lack of CD36 results in poorer short-term outcome from neonatal focal stroke due to lack of attenuation of NF-κB-mediated inflammation and diminished removal of apoptotic neuronal debris. Although inhibition of CD36 does not seem to be a good therapeutic target for protection after acute neonatal stroke, as it is after adult stroke, seeking better understanding of CD36 signaling in particular cell populations may reveal important therapeutic targets for neonatal stroke.