Periwound dopaminergic sprouting is dependent on numbers of wound macrophages.
Injury to many regions of the central nervous system, including the striatum, results in a periwound or 'abortive' sprouting response. In order to directly evaluate whether macrophages play an important role in stimulating periwound sprouting, osteopetrotic (op/op) mice, which when young are deficient in a variety of macrophage subtypes, were given striatal wounds and the degree of dopaminergic sprouting subsequently assessed. Two weeks postinjury, significantly fewer wound macrophages were present in the striata of op/op mice compared with controls (144 +/- 30.1 in op/op mice vs. 416.6 +/- 82.3 in controls, P < 0.005, analysis performed on a section transecting the middle of the wound). Dopamine transporter immunohistochemistry revealed a marked decrease in the intensity of periwound sprouting in the op/op group of animals. Quantification of this effect using [H3]-mazindol autoradiography confirmed that periwound sprouting was reduced significantly in the op/op mice compared with controls (71.4 +/- 21.7 fmol/mg protein in op/op mice vs. 210.7 +/- 27.1 fmol/mg protein in controls, P < 0.0005). In the two groups of animals the magnitude of the sprouting response in individuals was closely correlated with the number of wound macrophages (R = 0.83, R2 = 0.69). Our findings provide strong support for the crucial involvement of macrophages in inducing dopaminergic sprouting after striatal injury.
Batchelor
P E
PE
Departments of Medicine and Neurology, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg Victoria 3084, Australia.
Porritt
M J
MJ
Nilsson
S K
SK
Bertoncello
I
I
Donnan
G A
GA
Howells
D W
DW
D018759:Adrenergic Uptake Inhibitors; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002452:Cell Count; D003342:Corpus Striatum / Q000166:cytology / Q000293:injuries* / Q000378:metabolism; D003714:Denervation; D004298:Dopamine / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008454:Mazindol; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009416:Nerve Regeneration / Q000502:physiology*; D010022:Osteopetrosis / Q000235:genetics / Q000276:immunology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D014316:Tritium; D014945:Wound Healing / Q000502:physiology*
D018759:Adrenergic Uptake Inhibitors; D016177:Macrophage-1 Antigen; D014316:Tritium; D008454:Mazindol; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D004298:Dopamine