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

Abstract

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-

Selective Antibody-Induced Cholinergic Cell and Synapse Loss Produce Sustained Hippocampal and Cortical Hypometabolism with Correlated Cognitive Deficits

“…Typically, glucose use was depressed 3-4 days postexcitotoxin-lesion, but recovered to basal levels within 4 weeks after unilateral lesions, and 4 months following bilateral lesions despite sustained ChAT deficits (9,37,44,47,60,61,80). This functional recovery most likely reflects the lack of cholinergic selectivity of these lesion paradigms, leading to incomplete cholinergic denervation.…”

“…Hence glucose use changes seen 18 weeks postcholinergic neuronal loss reflect alterations in well organized, functional pathways associated with the basal forebrain cholinergic system. Several previous studies in both rats and baboons used different lesion paradigms to assess glucose utilization after disrupting BF cholinergic projections (9,37,44,47,60,61,80). However, these investigations were compromised by the lack of a discrete, selective cholinotoxin.…”

Transhemispheric diaschisis. A review and comment.

“…We limit this discussion to transhemispheric diaschisis, the terms "transhemispheric" or "interhemispheric" 11 being preferable to "transcallosal" because the contralateral effects of a unilateral insult may be mediated by neural pathways other than, or in addition to, the corpus callosum. 12 3 noted the importance of recovery of the deficits, or reversibility of the alterations, in diaschisis. Von Monakow wrote that "the effect of diaschisis, just as the effect of any type of shock, is in principle confined to a longer or shorter limited period (in its individual elements) and undergoes gradual regression in well-defined phases."…”

“…A decrease in CMRglu bilaterally, ipsilateral greater than contralateral, was noted at day 4, with no significant resolution through day 39 and only a trend for recovery of the hemispheric asymmetry. 12 The authors, commenting on such a unilateral lesion, noted that the contralateral metabolic effects operate through extracallosal mechanisms and that an intact corpus callosum is important for recovery of CMRglu after insult, at least for recovery as rapidly as with an intact corpus callosum. However, Meyer et al 13 found in baboons 24-48 hours after corpus callosum section that bilateral CBF was not decreased by the corpus callosum section alone.…”

“…Kempinsky performed most of his insults and electrical activity recordings weeks after callosal section. 3 Recent work by Yamaguchi et al, 12 -14 summarized in the "Review," measured glucose utilization with positron emission tomography in baboons after section of the anterior corpus callosum 14 and after section of the anterior corpus callosum plus unilateral lesioning of the nucleus basalis of Meynert several months later. 12 They performed the measurements days after the lesions were made; thus, these studies do not provide information regarding diaschisis in the very early period after insult.…”