In order to clarify the origins and pathways of vasoactive intestinal polypeptide (VIP)-containing nerve fibers in cerebral blood vessels of rat, denervation experiments and retrograde axonal tracing methods (true blue) were used. Numerous VIP-positive nerve cells were recognized in the sphenopalatine ganglion and in a mini-ganglion (internal carotid mini-ganglion) located on the internal carotid artery in the carotid canal, where the parasympathetic greater superficial petrosal nerve is joined by the sympathetic fibers from the internal carotid nerve, to form the Vidian nerve. VIP fiber bridges in the greater deep petrosal nerve and the internal carotid nerve reached the wall of the internal carotid artery. Two weeks after bilateral removal of the sphenopalatine ganglion or sectioning of the structures in the ethmoidal foramen, VIP fibers in the anterior part of the circle of Willis completely disappeared. Very few remained in the middle cerebral artery, the posterior cerebral artery, and rostral two-thirds of the basilar artery, whereas they remained in the caudal one-third of the basilar artery, the vertebral artery, and the intracranial and carotid canal segments of the internal carotid artery. One week after application of true blue to the middle cerebral artery, dye accumulated in the ganglion cells in the sphenopalatine, otic and internal carotid mini-ganglion; some of the cells were positive for VIP. The results show that the VIP nerves in rat cerebral blood vessels originate: (a) in the sphenopalatine, and otic ganglion to innervate the circle of Willis and its branches from anterior and caudally and (b) from the internal carotid mini-ganglion to innervate the internal carotid artery at the level of the carotid canal and to some extent its intracranial extensions.
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