Abstract WMP80: Cystathionine β Synthase Deficiency Exacerbates Cerebral Ischemia Reperfusion Injury Through Activation of the NMDA Receptor and Loss of Blood Brain Barrier Integrity in Mice

Hyperhomocysteinemia is a risk factor for stroke; however the mechanisms by which elevated homocysteine leads to stroke are poorly defined. In a murine model of cystathionine β synthase (CBS) deficiency, we tested the hypothesis that mild to severe elevation in plasma total homocysteine (tHcy) increases susceptibility to cerebral infarction through N-methyl-D-aspartate (NMDA) receptor activation and is associated with altered permeability of the blood brain barrier. We studied male Cbs-/- mice conditionally expressing a zinc-inducible mutated human CBS(I278T) transgene along with Cbs+/- and Cbs+/+ littermates at 10-14 weeks of age. The human transgene was allowed to express only until weaning to overcome the early mortality of Cbs-/- mice. A mild to severe increase in plasma total homocysteine levels (tHcy) were observed in Cbs+/- and Cbs-/- mice (6.1±0.3 and 309±18 μM respectively) compared with Cbs+/+ littermates (3.1±0.6 μM, Pu003c0.01). Experimental stroke was induced with middle cerebral artery occlusion...