NORMAL CEREBROVASCULAR REGULATORY MECHANISMS ARE PRESENT IN INTRACEREBRAL NEURONAL TRANSPLANTS

Local cerebral blood flow and local cerebral glucose utilization were measured using quantitative autoradiography in parallel groups of rats (n = 5-7) which 12-15 weeks previously had undergone limited unilateral ibotenate-induced lesion of the nucleus basalis magnocellularis, followed by implantation into ipsilateral neocortex of primordial basal forebrain cell suspensions. Surviving transplants were visualized by acetylcholinesterase histochemistry. Neither lesion alone nor the presence of a transplant produced significant side-to-side differences in either blood flow or glucose use in any of the 20 brain areas measured. Glucose use within the transplant was independent of the site of implantation. When sited in neocortex, glucose use in the transplant (66 +/- 4-mu-mol/100 g per min) was significantly lower than in the corresponding contralateral site (113 +/- 3-mu-mol/100 g per min), whereas when sited in subcortical white matter, glucose use (53 +/- 3-mu-mol/100 g per min) was significantly higher than in the contralateral side (29 +/- 4-mu-mol/100 g per min). In the host brain as a whole, the ratio of blood flow to glucose use ipsilateral to the transplant (m = 1.27, r = 0.88) was not significantly different from that of the contralateral side (m = 1.30, r = 0.94). This relationship was also observed within the transplanted tissue itself despite the fact that alkaline phosphatase histochemistry revealed a relative hypervascularization associated with the implantation site. The coupling of cerebral blood flow to metabolic demand in the transplant, evident under normal physiological conditions, remained intact in the face of experimentally induced hypercapnia, although the ratio of blood flow to glucose use was reset to a higher level in the host brain as a whole (m = 2.7, r = 0.96). Extrapolating these findings to the clinical situation it would appear that the therapeutic application of intracerebral transplantation techniques will not be compromised by cerebrovascular insufficiency in either the transplant or surrounding host brain.