Cerebrovascular innervation: adaptation to changes in metabolic demand and flow fluctuations in rats

Abstract

The heterogeneous nature of the basal cerebral arteries is well illustrated by the differences in the extent of innervation as found in different species as well as the variation in the degree of innervation during ageing and disease. To explain these differences, we postulated a coupling between variation in metabolic demand and corresponding flow fluctuations in the afferent arteries leading to adaptation of the nerve fibers in these arteries. This hypothesis was tested by inducing an experimental olfactory deficit or anosmia through intranasal application of zinc sulfate. It was shown that anosmia leads to a decrease in cholinergic- and nitrergic nerve fibers in the anterior cerebral artery, which coincides with a decreased metabolic activity in the olfactory bulb. Also, flow measurements revealed no changes in flow in the olfactory bulb after presenting a mixture of odorants into the nasal cavity in the anosmic rat. These facts support the above-mentioned postulation. The question remains how signaling from flow changes to the vessel wall and as a consequence alterations in nerve fiber densities take place. We propose a role for the parasympathetic neurotrophic factor neurturin in adaptation of the cholinergic- and nitrergic nerve fiber density in the anterior cerebral artery in the anosmic rat. Neurturin was infused during 14 days into the lateral ventricles, by using osmotic minipumps. Subsequently, immunohistochemical techniques were used to localize the parasympathetic nerves containing vesicular acetylcholine transporter and nitric oxide synthase in the basal cerebral arteries and the nerve fiber densities were quantified by image analysis. This analysis showed that neurturin infusion is able to prevent the decrease of nitrergic nerve fibers but not cholinergic nerve fibers in the anosmic rat. It is speculated that cholinergic fibers are supported by a different growth factor. It may be summarized that according to the results presented in the thesis, the following factors may cohere in determining local patterns of nerve fiber densities in the cerebral arteries: (1) metabolic demand, (2) flow changes, (3) availability of neurotrophic factors.