Intraventricular NGF infusion in the mature rat brain enhances sympathetic innervation of cerebrovascular targets but fails to elicit sympathetic ingrowth.
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.
Saffran
B N
BN
Department of Neurosurgery, University of Cincinnati School of Medicine, OH 45267.
Woo
J E
JE
Mobley
W C
WC
Crutcher
K A
KA
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002343:Carotid Artery, Internal / Q000294:innervation; D002536:Cerebral Arteries / Q000294:innervation*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009414:Nerve Growth Factors; D009638:Norepinephrine