Saffran, B. N., Woo, J. E., Mobley, W. C., and Crutcher, K. A. (1989). Intraventricular NGF infusion in the mature rat brain enhances sympathetic innervation of cerebrovascular targets but fails to elicit sympathetic ingrowth. Brain Research, 492(1-2):245-54.
Abstract
The ability of peripheral axons to regenerate long distances in the
peripheral nervous system (PNS) is well documented; however,
examples of axonal elongation within the adult mammalian central
nervous system (CNS) are rare. One example of axonal growth in the
mature brain is the sprouting of sympathetic axons into the
hippocampal formation following disruption of the septohippocampal
pathway. A current hypothesis is that elevated hippocampal NGF
levels, secondary to loss of retrograde transport by septal neurons,
elicits sympathetic ingrowth, In this study, we sought to determine
whether elevation of hippocampal NGF activity without septal
denervation is sufficient to elicit sympathetic sprouting. Forty-one
female rats were infused for two weeks with NGF or cytochrome C in
the right lateral ventricle through cannulae connected to an osmotic
minipump. In some animals the brains were sectioned and stained for
acetylcholinesterase (AChE) activity and norepinephrine
histofluorescence; in others, CNS tissue was assayed for nerve
growth factor (NGF) content with a two-site ELISA. A Farrand
microspectrophotometer was used to measure the intensity of
catecholamine fluorescence around the internal carotid artery. The
average fluorescence intensity of the sympathetic innervation of the
internal carotid artery in the NGF-injected animals was over twice
that of vehicle-injected rats indicating that the infused NGF was
both accessible to the sympathetic axons and biologically active.
However, in none of the cases with elevated hippocampal NGF levels
were sympathetic axons observed within the hippocampal formation or
any other brain region. These results suggest that simple elevation
of brain NGF, while perhaps necessary, is insufficient to permit the
growth of sympathetic axons into the mature mammalian CNS.
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