Immunohistochemical evidence for the absence of central neuron projection to pial blood vessels and dura mater.

The present work shows that, in rat pial vessels and dura mater, all the nerve fibres observable by confocal fluorescence microscopy belong to the peripheral nervous system. It has been postulated that central nervous structures such as the raphe nuclei and the locus coeruleus could send direct projections to meningeal blood vessels. Mature neurons, whose perikaryons and axons are entirely located within the central nervous system, express the low molecular mass neurofilament protein and not the 57,000 mol. wt intermediate filament protein called "peripherin". This is the case for both raphe nuclei and locus coeruleus neurons [Leonard et al. (1988) J. Cell Biol. 106, 181-193]. Neurons which send axons outside the central nervous system or ganglionic neurons of the peripheral nervous system systematically express both proteins [Portier et al. (1984) Devl Neurosci. 6, 335-344]. Double labelling of pial vessels and meningeal tissue with antibodies directed against low molecular mass neurofilament and peripherin revealed nerve fibres immunoreactive to both antibodies and no nerve fibres reactive only to the low molecular mass neurofilament antibody. Conversely, cortical nerve fibres were immunoreactive only to the low molecular mass neurofilament antibody. It is thus concluded that the raphe nuclei and the locus coeruleus do not directly innervate meningeal tissues and, therefore, that these nuclei cannot directly intervene in cerebrovascular pathologies such as migraine headache or vasospasm. Secondarily, the present work also allowed for the first time the accurate observation of the spatial organization of the complete cerebrovascular innervation. Three main types of nerves can be defined on a morphological basis. A high proportion of these nerve fibres, either isolated or grouped in bundles, are varicose nerve fibres. Contacts between adjacent varicosities of the same type, which have been occasionally observed by electron microscopy, appear to be a very frequent feature.