title: The development of glucose intolerance after focal cerebral ischemia participates in subsequent neuronal damage.
abstract: Hyperglycemia is a known exacerbating factor in ischemic stroke; however, most information is limited to pre-ischemic hyperglycemia, while little is known about post-ischemic hyperglycemia. In addition, it has been clinically reported that hyperglycemia can develop after stroke, but the detailed mechanisms underlying this are unknown. Here, we focused on the relationship between post-ischemic hyperglycemia and the development of neuronal damage. In particular, we investigated the time course of alterations in fasting blood glucose levels (FBG) and the development of neuronal damage, including neuronal death (the development of infarction), behavioral abnormality and memory disturbance, using middle cerebral artery occlusion (MCAO) model mice. The neuronal death was observed from 6 h, reaching a maximum on day 3 and was gradually aggravated up to day 5 after MCAO. Interestingly, 12 h and 1 day after MCAO, FBG was significantly increased and insulin sensitivity and insulin secretory capacity were decreased on 1 day after MCAO. In addition, we found that the basal plasma insulin levels were significantly higher and adiponectin levels were significantly lower on day 1 in the MCAO group compared with the sham group. These results indicate that the development of glucose intolerance was observed on day 1. Importantly, the neuronal damage observed on day 3 was completely suppressed by continuous administration of insulin during the first 48 h after MCAO. These results suggest that the post-ischemic hyperglycemia in the early phase of ischemic stress may be involved in the development of neuronal damage.
authors.affiliation: Department of Clinical Pharmacy, Kobe Gakuin University, Faculty of Pharmaceutical Sciences, Chuo-ku, Kobe, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Harada
authors.forename: Wakako Hamabe
authors.initials: WH
authors.lastname: Fujita
authors.forename: Kanako
authors.initials: K
authors.lastname: Shichi
authors.forename: Shogo
authors.initials: S
authors.lastname: Tokuyama
mesh_terms: D052242:Adiponectin / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D005215:Fasting / Q000378:metabolism; D018149:Glucose Intolerance / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D013997:Time Factors
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D007328:Insulin