Cell Death After Exposure to Subarachnoid Hemolysate Correlates Inversely With Expression of CuZn–Superoxide Dismutase

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Abstract
Background and Purpose —Subarachnoid hemolysate (SAH) has been associated with oxidative brain injury, cell death, and apoptosis. We hypothesized that over-expression of CuZn–superoxide dismutase (CuZn-SOD) would protect against injury after SAH, whereas reduction of its expression would exacerbate injury. Methods —Saline (n=16) or hemolysate (n=50) was injected into transgenic mice overexpressing CuZn-SOD (SOD1-Tg), CuZn-SOD heterozygous knockout mutants (SOD1+/−), and wild-type littermates (Wt). Mice were killed at 24 hours. Stress gene induction was evaluated by immunocytochemistry and Western blotting for hemeoxygenase-1 and heat shock protein 70. Apoptosis was evaluated by 3′-OH nick end-labeling and DNA gel electrophoresis. Cell death was quantified through histological assessment after cresyl violet staining. Results —Histological assessment demonstrated neocortical cell death in regions adjacent to the blood injection. Overall cell death was reduced 43% in SOD1-Tg mutants (n=6) compared with Wt littermates (n=6; P 40% in SOD1+/− mutants (n=6; P Conclusions —The extent of CuZn-SOD expression in the cytosol correlates with cell death after exposure to SAH in a manner separate from apoptosis. Overexpression of CuZn-SOD may potentially be an avenue for therapeutic intervention.