title: Cerebral blood flow, glucose metabolism and tunel-positive cells in the development of ischemia.
abstract: Few in vivo studies were available about the relation between cerebral blood flow, glucose metabolism and the appearance of apoptotic cells in the development of cerebral infarct. To investigate this, we measured local cerebral blood flow (lCBF), local cerebral metabolic rate in glucose (lCMRglc), and histopathology in transient focal cerebral ischemia in the rat. A unilateral middle cerebral artery occlusion (MCAO) was induced for 2 h in Wistar-ST rats (n = 42). A histopathological study with hematoxylin-eosin staining and the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method was performed. lCBF was measured by means of the (14)C-iodoantipyrine autoradiography technique during MCAO (n = 6), and 1, 22 and 70 h after reperfusion. lCMRglc was also measured by autoradiography with (14)C-2-deoxyglucose in the animals 22 h after reperfusion. These parameters were assessed in each region of interest: the ischemic core, boundary zones (BZ-I and BZ-II) and remote area. The boundary zones were defined as the area based on TUNEL positivity (more than 5/field) at 22 h after reperfusion (BZ-I) and at 70 h after reperfusion (BZ-II). In the BZ-I, lCBF was decreased to 18% of the control during MCAO, and lCBF and lCMRglc showed 44 and 62% of the control, respectively, 22 h after reperfusion. In this area, TUNEL-positive cells increased at 22 h, then markedly decreased 70 h after reperfusion. In the BZ-II, lCBF decreased to 39% of the control during MCAO, then returned to about 90% of the control 22 h after reperfusion. lCMRglc was maintained near its normal range (82% of the control) 22 h after reperfusion. Histopathology of BZ-II was normal 22 h after reperfusion. The TUNEL positivity of neurons in our study was assumed to be a marker of apoptotic cells. Our data suggested that the apoptotic process plays an important role in the maturation of a cerebral infarct. Both lCBF and lCMRglc were maintained with only a mild reduction in the predisposing phase of apoptosis, suggesting that sufficient blood supply and glucose metabolism are required to promote the process of apoptosis.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan. terada33@ipc-tokai.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Terada
authors.forename: S
authors.initials: S
authors.lastname: Inao
authors.forename: N
authors.initials: N
authors.lastname: Mizutani
authors.forename: H
authors.initials: H
authors.lastname: Tsukada
authors.forename: J
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D005947:Glucose / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005947:Glucose