The Journal of Neuroscience, February 1, 2000, 20(3):1036-1043
Nitric Oxide Influences Injury-Induced Microglial Migration and
Accumulation in the Leech CNS
Aileen
Chen1,
Shanta M.
Kumar2,
Christie
L.
Sahley2, and
Kenneth J.
Muller1
1 Department of Physiology and Biophysics,
University of Miami School of Medicine, Miami, Florida 33136, and
2 Department of Biological Sciences, Purdue University,
West Lafayette, Indiana, 47907
Damage to the leech or mammalian CNS increases nitric oxide
(NO) production and causes accumulation of phagocytic microglial cells
at the injury site. The aim of this study was to determine whether NO
plays a role in microglial migration and accumulation at lesions in
which NO is generated by a rapidly appearing endothelial nitric oxide
synthase (eNOS) in leeches. Immunohistochemistry and cytochemistry
demonstrated active eNOS before and throughout the period of microglial
accumulation at the lesion. Decreasing NO synthesis by application of
the NOS inhibitor
Nw-nitro-L-arginine
methyl ester (1 mM) significantly reduced microglial accumulation, whereas its inactive enantiomer
Nw-nitro-D-arginine methyl
ester (1 mM) resulted in microglial
accumulation similar to that in crushed controls. Increasing NO with
the donor spermine NONOate (SPNO) (1 mM) also inhibited
accumulation, but not in the presence of the NO scavenger
2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-oxyl-3-oxide (50 µM). The effect of SPNO was reversed by washout. SPNO
application reduced average microglial migratory speeds and
even reversibly arrested cell movement, as measured in living nerve
cords. These results suggest that NO produced at a lesion may be a stop
signal for microglia to accumulate there and that it can act on
microglia early in their migration. Thus, NO may assume a larger role
in nerve repair and recovery from injury by modulating accumulation of
microglia, which appear to be important for axonal regeneration.
Key words:
nitric oxide; cell migration; endothelial nitric oxide
synthase; Hirudo medicinalis; nerve repair; nerve
regeneration; microglia
Copyright © 2000 Society for Neuroscience 0270-6474/00/2031036-08$05.00/0
Previous Article | Next Article
