Hemorrhagic transformation induced by acute hyperglycemia in a rat model of transient focal ischemia.

Hemorrhagic transformation (HT) is a major factor limiting the use of tissue plasminogen activator for stroke. HT has been found in animals undergoing transient focal cerebral ischemia with hyperglycemia. This study examined the incidence rate, location and content of HT.Rats were divided into two groups: the hyperglycemic group and normoglycemic group. Rats received an injection of 50% glucose (6 ml/kg, i.p.) or an equivalent volume of saline 15 min before 2-h transient middle cerebral artery occlusion (tMCAO) with reperfusion. Rats were killed 4, 8 or 24 h later and used for blood-brain barrier permeability, hemoglobin content, brain edema, and infarct volume measurements. Mortality and HT incidence rates were also evaluated. We found that all hyperglycemic rats had HT, and two out of six normoglycemic rats had HT 24 h after tMCAO. Hyperglycemic rats had more severe Evans blue leakage (p<0.05) and brain edema (p<0.05) in the ipsilateral hemisphere. However, infarct volumes were the same in hyperglycemic and normoglycemic rats. In conclusion, acute hyperglycemia reliably and consistently resulted in hemorrhagic transformation in a rat model of transient focal cerebral ischemia. The model is useful for experimental assessment of new therapies for HT.