The Change Of Insulin-like Growth Factor-1 And The Affection On Neurogenesis After Ischemic Brain Injury

Insulin-like growth factor- l(IGF-l) is one important part of insulin-like growth factor system. IGFs regulate the metabolism of the blood glucose and play an important role in proliferation,differentiation and maturation of tissues. 1GF-1 is a polypetide hormone that has demonstrated effects on these neural progenitor cells. Neural stem cell (NSC) is regard as clone cell cluster which has a function of renewing and differentiation.After ischemic brain injury in adult rats ,the level of IGF-1 changes, and it takes part in stimulateing proliferation, migration and differentiation of NSC. These two parts elucidate the changes of insulin-like growth factor -l(IGF-l) and the affection on neurogenesis after ischemic brain injury.We hope it might provide a new way to prevent from cerebral ischemic damage.Part I The research of the changes of Glu,Insulin and IGF-1 in serum of newborn infants with HIEHypoxic-ischemic encephalopathy (HIE) is one kind of severe complication after asphyxia of the newborn infants. It is serious and its mortality and morbidity are very high. It can turn out permanent neural dysfunction .Recent research results have showed that both IGF-1 and Ins play an important role in CNS and they are connected with pathological process of HIE. Animal test showed that IGF-1 prevent neuron from damage after HIE.and it anticipates in the repairing procedure after HIE . Thisexperiment is to illuminate the changes and relations of the Glu Ins , IGF-1 after hypixic ischemic encephalopathy (HIE) and the protective role which Ins , IGF-1 worked on neuron.MethodsHIE 50cases, among them,the serious group 15 cases, the moderate group 17 cases, the light group 18 cases. Normal Control group 20 cases. 2ml blood was drown in the vein of each newborn infant in acute and rehabilitated period individually, the quantity of IGF-1 in serum is detected by radioimmunoassay (RIA), the quantity of Ins in serum is detected by chemiluminescence immunoassay (CLIA), the quantity of glucose in serum is detected by the instrument with type of Rokangquan TM accutive. The umbilical vein blood 2ml were drawn from 20 cases of controls after birtl .The indexes were detected by the same methods.Results1 In acute period ,the level of IGF-1 reduced obviously in serum of the newborn infants with HIE,and Glu increased obviously. There is a negative correlation between IGF-1 and Glu. The changes related with newborn infants' complications. In rehabilited period ,the Glu get to normal, the IGF-1 was a little higher than that of in acute period . but it still lower than that of control group. There was negative correlation between IGF-1 and Glu.2 The level of Ins in serum of the newborn infants with HIE had no obvious changes compairing with the control group in acute period and rehabilited period. It has no relations with Glu Ins.Conclusion1 It approved that IGF-land Glu in serum of the newborn infants with HIE had obvious ly changed. There is a negative correlation between IGF-1 and Glu.2 IGF-1 anticipates in the repairing procedure after HIE.Part II Effects of IGF-1 on neurogenesis after Ischemic brain injury in adult ratsIschemic brain injury can stimulate the proliferation of NSC which is regulated by changes of microcircumstance. The microcircumstance inculde some growth factors which is excreted by partial cells. Growth factors is a big family , IGF-1 is one important part of Growth factor system. This experiment is to elucidate effects of IGF-1 on neurogenesis after ischemic brain injury in adult rats. MethodsCerebral middle artery occlusion operations(MCAO) rats using health male SD rats were set up, then IGF-1 (5uJ/l|ig) was infused into the lateral ventricular. To evalute neurogenesis, bromodeoxyuridine (BrdU), high polysialylated neural cell adhesion molecular (PSA-NCAM), microtubule-associated protein (MAP2) were choosed as the makers of proliferation and migration, respectively. BrdU-labeled cells. PSA-NCAM-labeled cells, BrdU-labeled cells with PSA-NCAM expression (BrdU-PSA-NCAM-labeled cells) BrdU-labeled cells with MAP2 expression (BrdU-MAP2-labeled cells) were identified with immunohistochemistry staining and double immunohistochemistry staining.ResultsBrdU-ladeled cells and PSA-NCAM-labeled cells increased approximately by 4.0-fold and 1.8-fold (compared with the MCAO control groups) respectiely, and 9.9-fold and 5.4-fold(compared with the sham-operated groups respectively. They all reached the peak at 7d after MCAO. BrdU-labeled cells with PSA-NCAM expression (BrdU-PSA-NCAM-labeled cells) were first detected both in the SVZ and DG 4d after MCAO with a peak of 7d after ischemia and gradually decreased after that. But BrdU-labeled cells with MAP2 gradually increased from 14d after ischemia.Conclusion1 The study verified that NSC exist in the CNS of adult brain.2 The study verified that neurogenesis exists after focal ischemia in CNS of adult brain.3 The study proved that IGF-1 induced the neurogenesis after ischemia cerebral injury.