By means of histochemical fluorescence techniques, evidence has been obtained for regenerative sprouting of axons from catecholamine neurons in the rat mesencephalon 1–7 weeks after electrolytic destruction of the substantia nigra and part of the ventromedial midbrain tegmentum. Three days after the lesion, accumulations of catecholamine occurred in coarse, beaded and distorted fibers on the borders of the lesion within the ascending catecholamine fiber tracts. Such catecholamine accumulations in proximal portions of severed axons or axon collaterals are well known; these accumulations showed a progressive decrease after approximately 1 week. In the present study an additional phenomenon was discovered between 7 and 19 days after lesion, namely the appearance of numerous, densely packed, fine, varicose, fluorescent fibers, probably identical with sprouts from catecholamine neurons. These fibers had an abnormal distribution outlining the lesion border and the electrode tracks, sometimes coursing through the lesion and even invading the walls of blood vessels penetrating, or situated close to, the lesion. These numerous newly appearing fluorescent fibers, including those invading the blood vessel walls, were equally prominent in animals with their intracranial arteries sympathectomized by bilateral removal of the superior cervical ganglia. Hence, these fibers were of central origin. The fluorescence of the newly formed fibers was characteristic for catecholamines, and the presence of noradrenaline could be established by means of microspectrofluorometric analysis in fibers invading sympathectomized vascular walls. Although the catecholamine fluorescence in the abnormal fibers on the border of the lesion had decreased at 7 weeks, it persisted in the new fibers invading the vessel walls, which may thus constitute a terminal area of distribution for the regenerating central catecholamine neurons. The phenomenon of regenerative sprouting in the central nervous system has previously been demonstrated, but this is the first direct evidence of regeneration of central monoamine fibers.
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