OVEREXPRESSION OF HUMAN DOWN SYNDROME CANDIDATE REGION 1 (DSCR1) GENE IS PROTECTIVE IN STROKE

Abstract

The Down syndrome candidate region 1 (DSCR1) gene is found on chromosome 21. DSCR1 protein is highly expressed in the brain, and following middle cerebral artery occlusion (MCAO) in mice DSCR1 mRNA and protein increases in the peri‐infarct region. We examined the effect of overexpression of DSCR1 on outcome following stroke. DSCR1 transgenic (Tg) mice were produced by the overexpression of the human DSCR1 gene, only in cells that normally express DSCR1, on a C57Bl6/J X CBA background. Cerebral ischemia was induced by MCAO for 0.5 h followed by reperfusion for 23.5 h (ischemia‐reperfusion; I‐R) in 8–14 week old male DSCR1 Tg (n=14) and wild‐type (Wt; n=9) mice. After 24 h, neurological impairment was assessed (neurological score and hanging wire test). Brain infarct and edema volume were then measured in thionin‐stained coronal sections. After I‐R, Tg mice had less neurological impairment than Wt, with a lower neurological score (2.4±0.3 vs 3.9±0.1; P<0.05) and a longer hanging‐wire time (38±5 vs 9±3 s; P<0.01). After I‐R, Tg mice had a significantly smaller subcortical infarct volume than Wt mice (15±2 vs 32±5 mm3; P<0.01). In addition, total infarct volume tended to be smaller in Tg than Wt mice (26±5 vs. 36±6 mm3; P=0.26). Furthermore, edema volume was smaller in Tg than Wt mice (17±3 vs 31±6 mm3; P<0.05). Thus, overexpression of DSCR1 improves outcome following stroke.