Ameliorating effect of hypothalamic brain-derived neurotrophic factor against impaired glucose metabolism after cerebral ischemic stress in mice

Brain-derived neurotrophic factor (bdnf),a member of the neurotrophin family,has potent neuroprotective effects against brain injury. we recently reported that glucose intolerance/ hyperglycemia could be induced by ischemic stress (i.e.,post-ischemic glucose intolerance) following ischemic neuronal damage. therefore,the aim of this study was to determine the effects of bdnf on the development of post-ischemic glucose intolerance and ischemic neuronal damage. male ddy mice were subjected to middle cerebral artery occlusion (mcao) for 2 h. on day 1,the expression levels of bdnf were significantly decreased in the cortex,hypothalamus,liver,skeletal muscle,and pancreas. the expression levels of tyrosine kinase b receptor,a bdnf receptor,decreased in the hypothalamus and liver and increased in the skeletal muscle and pancreas,but remained unchanged in the cortex. intrahypothalamic administration of bdnf (50 ng/mouse) suppressed the development of post-ischemic glucose intolerance on day 1 and neuronal damage on day 3 after mcao. in the liver and skeletal muscle,the expression levels of insulin receptors decreased,while gluconeogenic enzyme levels increased on day 1 after mcao. these changes completely recovered to normal levels in the presence of bdnf. these results indicate that regulation of post-ischemic glucose intolerance by bdnf may suppress ischemic neuronal damage. © the japanese pharmacological society.