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- W2801806511 abstract "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 beta synthase (CBS) deficiency, we investigated whether mild to severe elevation in plasma total homocysteine (tHcy) increases susceptibility to cerebral infarction and if this phenotype is associated with loss of blood brain barrier (BBB) integrity. 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. Experimental stroke was induced with middle cerebral artery occlusion for one hour followed by 24 hours of reperfusion. TTC stained coronal sections were used to quantify the infarcted area. BBB integrity was assessed prior to injury using a standard Evan’s blue (EB) infusion method. Leakage of EB was quantified in brain homogenates and normalized to brain weight. Mild to severe increases in plasma 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, P<0.01). Both Cbs +/- and Cbs -/- mice exhibited significant increases in infarct size following ischemia-reperfusion injury as compared to Cbs+/+ mice (12.2±3% in Cbs+/+ mice vs. 35.1±7.7% in Cbs+/- and 27.7±7.8% in Cbs-/- mice, P<0.05). A significant increase in EB extravasation was observed in Cbs+/- and Cbs -/- mice (3.8±0.8 and 4.8±0.2 μg/g, respectively) compared to Cbs+/+ mice (1.7±0.4 μg/g, P<0.05). The similarity in extent of cerebral infarction observed in Cbs+/- and Cbs-/- mice suggests a threshold effect and that a mild increase in tHcy is enough to disrupt BBB integrity and produce a severe stroke phenotype in experimental murine models." @default.
- W2801806511 created "2018-05-17" @default.
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- W2801806511 date "2017-05-01" @default.
- W2801806511 modified "2023-09-26" @default.
- W2801806511 title "Abstract 146: Deficiency of Cystathionine beta Synthase Alters Blood Brain Barrier Integrity and Exacerbates Cerebral Ischemia Reperfusion Injury in Mice" @default.
- W2801806511 doi "https://doi.org/10.1161/atvb.37.suppl_1.146" @default.
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