Evidence that punctate intracerebral administration of 6-hydroxydopamine fails to produce selective neuronal degeneration. Comparison with copper sulfate and factors governing the deportment of fluids injected into brain.

Abstract

Various doses of 6-hydroxydopamine (6-OHDA) and copper sulfate were injected into brain regions having a different composition of monoamine-containing neurons: The red nucleus, substantia nigra-ventral tegmental area, caudate-putamen nucleus, and thalamus. Brains were subsequently histochemically processed for acetylcholinesterase and NADH-diaphorase activities and for cupric ion; traditional histology was also performed. A maximum of four regions of neuropathology was observed occurring successively in relation to the cannula: (1) A zone of complete absence of neural, glial, and vascular elements due to tissue displacement by the cannula, (2) an area consisting of a dense layer of glia cells 0.05–0.2 mm thick immediately surrounding the cannula tract, (3) a region exhibiting virtually complete loss of neural elements accompanied over time by extensive gliosis, and (4) a zone of neuronal loss probably occurring as a function of retrograde degeneration and/or reaction to other injury processes. Intracerebral insertion of the cannula without fluid infusion or injections of the respective vehicles of CuSO4 and 6-OHDA produced Zone 1 and 2 degeneration at all sites tested; Zone 4 damage was also seen but reliably only in the red nucleus and substantia nigra. Injection of solutions of 6-OHDA and CuSO4 produced Zone 1, 2, and 3 degeneration at all target areas tested. Zone 3 damage was the most prominent neuropathology, and Zone 4 cell loss was observed only in relation to the special anatomical characteristics of the neurons in the brain region infused. It was found that the degree of myelination of a particular brain region markedly influenced the nature and extent of Zone 3 damage.