Effects of insulin on vascular diameter of the peri-infarct region and infarct volume after cerebral infarction in mice

Abstract

Objective To investigate the effects of insulin on vascular diameter of the peri-infarct region and infarct volume after cerebral infarction in mice. Methods Forty male C57/BL6j mice were randomly divided into a control group (n=5), a cerebral infarction group (n=15), a cerebral insulin resistance group (n=5), and a cerebral insulin resistance infarction group (n=15). A model of cerebral infarction was induced by the photochemical method. A model of cerebral insulin resistance was induced by intracerebroventricular injection of streptozocin. Two-photon confocal microscope was used to in vivo evaluate the changes of vascular diameter in the peri-infarct region at 20 min after insulin injection into the cerebellomedullary cistern. After modeling of cerebral infarction, artificial cerebrospinal fluid or insulin (10 ng/ml) was immediately injected into the cerebellomedullary cistern, and the effect of insulin on cerebral infarct volume was evaluated at 24 h after infarction. Results Insulin did not have significant effect on various types of cerebral vascular diameters in the normal control group, but it significantly contracted cerebral arteries (-23.16%±6.86% and -23.32%±6.40%, respectively; all P<0.001) and penetrating arteries (-15.20%±5.51% and -16.40%±4.27%, respectively; all P<0.001) in the cerebral insulin resistance group and the cerebral insulin resistance infarction group, but it did not have any effect on the diameters of the cerebral veins. There were no significant differences in the vasoactive effects of insulin between the cerebral infarction group and the normal control group, as well as between the cerebral insulin resistance group and the cerebral insulin resistance infarction group. Insulin significantly reduced the volume of cerebral infarction in the cerebral infarction group (9.0±1.0 mm3vs. 6.0±1.2 mm3;t=4.294, P=0.002), and it did not have significant effect on the volume of cerebral infarction in the cerebral insulin resistance infarction group (12.6±2.3 mm3vs. 11.6±1.7 mm3;t=0.782, P=0.456). Conclusions Insulin can reduce ischemic brain injury in normal mice and can not affect the cerebrovascular diameter of the peri-infarct region. The neuroprotective effect of insulin is not significant in cerebral insulin resistance in mice, and it may be associated with the vasoconstrictor effects of insulin in the peri-infarct region. Key words: Cerebral Infarction; Brain Ischemia; Insulin; Insulin Resistance; Microcirculation; Vasodilation; Mice