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NGF‐dependent And NGF‐independent Recovery Of Sympathetic Function After Chemical Sympathectomy With 6‐hydroxydopamine

A. Gloster, J. Diamond
Published 1995 · Biology, Medicine

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To help clarify the distinction between the nerve growth factor (NGF)‐dependent collateral sprouting of sympathetic nerves and their NGF‐independent regeneration after crush, we used 6‐hydoxydopamine (OHDA) to destroy the sympathetic terminals in adult rats; this leaves the axons damage‐free. Would recovery occur by regeneration and/or collateral sprouting? A single 6‐OHDA injection abolished the sympathetic pilomotor field revealed by electrical stimulation of a cutaneous nerve. Recovery began within 2 days, and by 20 days the field was reestablished. If the field was “isolated” by adjacent denervations at the time of 6‐OHDA treatment, the recovering pilomotor field expanded extensively into the surrounding territory. In the presence of anti‐NGF, however, the pilomotor field expansion ceased at about 60% of its former size; if anti‐NGF treatment was discontinued, expansion recommenced and extended into the surrounding skin. We suggest that the latter, NGF‐dependent, growth phase corresponds to collateral sprouting, and the initial NGF‐independent one to regeneration. After simple nerve crush, however, such regeneration can triple the normal sympathetic field size. This difference between crush‐ and 6‐OHDA‐induced regeneration might relate to the “cell body reaction” (CBR); the CBR is reduced with increasing distance of the lesion and is undetectable after a 6‐OHDA lesion. Since the CBR and the vigor of regeneration are both increased by repeated axonal injury, we tested the effects of multiple 6‐OHDA treatments; this significantly increased the initial NGF‐independent expansion. We hyprthesize that regeneration is regulated largely by mechanisms associated with the CBR, and that neurotrophin‐dependent collateral sprouting occurs independently of these. © 1995 Wiley‐Liss, Inc.
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