Experimental Study of Distant Effects of Acute Focal Brain Injury

Summary: This study examines the correlation between local CMRglc (LCMRglc) alterations and clinicopatholog ical changes in a chronic middle cerebral artery (MCA) occlusion model in the cat. The left MCA was occluded for a period of 2 h. The animals were grouped into mild, moderate, and severe ischemia based on the depression of the EEG 30 min after the MCA occlusion. Follow ing release of the clip, the animals were allowed to re cover for a week during which time daily neurological examinations were performed. On the seventh day P4C]2-deoxyglucose was injected for the determination of LCMRglc• Alternative blocks were processed for histo logical evaluation in which both neuronal and phagocytic changes were graded into four categories (0 = normal to 3 = severe). LCMRglc (J.LmollIOO glmin) in the ischemic hemisphere (all histological grades) was significantly lower than the metabolic rate in comparable regions of the sham MCA occlusion group. Regions with significant phagocytosis (grade 2 and 3) invariably exhibited acti vated glucose metabolism (57.4 ± 8.4 and 105.9 ± 6.8 J.Lmol/lOO glmin, respectively), which was significantlyThe recovery process of brain tissue after an isch emic insult may be closely related to its metabolic state. Although the recent development of positron emission tomography has offered the potential for investigating glucose metabolism of the human brain Phelps et al., 1982), few studies have been made early following a stroke (Kuhl et al., 1980;Lenzi et al., 1982;Wise et al., 1983;Baron et al., 1984;Kushner et al., 1987). These findings provided some information about Abbreviations used: 2-DG, 2-deoxyglucose; LC, lumped con stant; LCMRgl c, local CMRglc; MCA, middle cerebral artery. 535higher than in regions without phagocytosis (30.4 ± 0.8 J.LmolllOO g/min). There was a significant gradient of me tabolism in the central, peripheral, and boundary zone and the non-MCA territory in the animals with severe ischemic lesions. LCMRglc in the central MCA territory was well correlated with the EEG amplitude changes (r = 0.82, p < 0.05) and the morphological score (r = -0.89, p < 0.05). The metabolic rate was significantly depressed in both the ipsilateral and the contralateral central MCA territories in comparison with the sham occlusion ani mals. The depression in LCMRglc in the contralateral hemisphere correlated well with the concomitant depres sion in the contralateral EEG amplitude. These studies demonstrate that local heterogeneous metabolic alter ations and contralateral cortical diaschisis exist chroni cally following temporary MCA occlusion and that the increases in local cerebral glucose metabolism seen in chronic stroke may be due to phagocytotic activity.

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Local Cerebral Glucose Utilization in Chronic Middle Cerebral Artery Occlusion in the Cat

Komatsumoto

Greenberg²,

Hickey

et al. 1989

“…That this phenomenon is mediated via transcallosal fi bers is suggested by Kempinsky's early studies (Kempinsky, 1958). The suppression of regional blood flow in thalamus and basal ganglia ipsilateral to a zone of cortical infarction (Celesia et aI., 1984;Dietrich et aI., 1986b) may be a mechanistically sim ilar form of diaschisis, i.e., mediated transneuron ally.…”

Section: Discussionmentioning

confidence: 97%

Acute Thrombotic Infarction Suppresses Metabolic Activation of Ipsilateral Somatosensory Cortex: Evidence for Functional Diaschisis

Ginsberg

Castella

Dietrich

et al. 1989

Summary:To study the effects of focal infarction on the capacity for functional activation of an ipsilateral somato sensory system remote from the lesion, we produced a small thrombotic infarct in the left frontal pole of male Wi star rats by a photochemical method. Five days later, the awake, restrained rats received tactile stimulation of the large whiskers (vibrissae) of the right side of the face, while a double-label 14C-autoradiographic study of local CMRglc (lCMRgJc) and local CBF (lCBF) was performed. Unlesioned and unstimulated animals served as controls. In rats without frontal infarct, vibrissae stimulation led to activation of ICMRglc in the three synaptic relay stations of the barrel-field pathway (ipsilateral trigeminal medul lary nucleus, contralateral ventrobasal thalamus, and contralateral barrel-field cortex). The mean increment in ICMRglc was 42% in lamina IV of barrel-field cortex and 49% in ventrobasal thalamus. Normalized ICBF tended to increase in superficial cortical laminae. In unstimulated animals with frontal infarct, ICMRglc was reduced by 20-30% throughout the ipsilateral barrel-field cortex asThe concept of diaschisis-an acute or subacute suppression of neural function in intact brain re gions remote from a site of primary injury-has at tracted increasing attention as one of several factors possibly relevant to functional recovery after isch emic stroke (Feeney and Baron, 1986). Although the application of modern techniques for assessing regional brain function has contributed importantly

“…"Transcallosal diaschisis" has long been im plicated in the reductions in electrophysiological re sponses (Kempinsky, 1958), metabolic rates of glu cose and oxygen, and blood flow observed in the cerebral cortex contralateral to focal cortical dam age (for review see Feeney and Baron, 1986); in unilateral lesions of subcorticocortical projection systems (e.g., thalamo-or basalocortical), the CC was also thought to mediate the contralateral effects as a result of ipsilateral cortical hypometabolism (Girault et aI., 1985;Baron et aI., 1986;Cambon et aI., 1987;Kiyosawa et aI., 1989). In favor of this hypothesis, Yamaguchi et ai.…”

Section: Discussionmentioning

confidence: 99%

Effects of Unilateral Lesion of the Nucleus Basalis of Meynert on Brain Glucose Utilization in Callosotomized Baboons: A PET Study

Yamaguchi

Kunimoto

Pappatà

et al. 1990

Summary: Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in ba boons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides de spite persistent deficit in cortical ChAT activity. To in vestigate the role of the corpus callosum (CC) in this bi lateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion >3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by posThe nucleus basalis of Meynert (NbM) is the ma jor source of cholinergic projections to the cerebral cortex (Mesulam and Van Hoesen, 1976) and is con sistently involved in dementia of the Alzheimer type (Ezrin-Waters and Resch, 1986;Salamone, 1986;Olton and Wenk, 1987). The effects of cholin ergic deafferentation, obtained by unilateral stereo taxic NbM lesions, on the energy metabolism of the cerebral cortex are of interest because both cortical glucose utilization and oxygen consumption are re-