Cerebral blood flow, glucose metabolism and TUNEL-positive cells in the development of ischemia

Few in vivo studies were available about the relation between cerebral bloo d flow, glucose metabolism and the appearance of apoptotic cells in the dev elopment of cerebral infarct. To investigate this, we measured local cerebr al blood flow (ICBF), local cerebral metabolic rate in glucose (ICMRglc), a nd histopathology in transient focal cerebral ischemia in the rat. A unilat eral 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 perf ormed. ICBF was measured by means of the C-14-iodoantipyrine autoradiograph y technique during MCAO (n = 6), and 1,22 and 70 h after reperfusion. ICMRg lc was also measured by autoradiography with C-14-2-deoxyglucose in the ani mals 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 rep erfusion (BZ-II). In the BZ-I, ICBF was decreased to 18% of the control dur ing MCAO, and ICBF and ICMRglc showed 44 and 62% of the control, respective ly, 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, ICBF d ecreased to 39% of the control during MCAO, then returned to about 90% of t he control 22 h after reperfusion. ICMRglc was maintained near its normal r ange (82% of the control) 22 h after reperfusion. Histopathology of BZ-II w as normal 22 h after reperfusion. The TUNEL positivity of neurons in our st udy 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 cerebr al infarct. Both ICBF and ICMRglc were maintained with only a mild reductio n in the predisposing phase of apoptosis, suggesting that sufficient blood supply and glucose metabolism are required to promote the process of apopto sis. Copyright (C) 2001 S. Karger AG, Basel.