Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve.
OBJECTIVE
A group B-streptococcus exotoxin (CM101) was administered following optic nerve injury in adult rats in order to analyze putative effects on macrophages, glial scar formation and regrowth of axons in the lesioned optic nerve.


METHODS
After a standardized intraorbital optic nerve crush, animals were randomized to treatment with CM101 (30 microm/kg body weight, iv, repeated every other day) or vehicle alone. Morphology (semithin sections) and immunohistochemistry directed towards macrophages (ED1), neurofilament (NF), astrocytes (GFAP) and regenerative sprouts (GAP43) were employed at different time-points up to 28 dpi.


RESULTS
A significant increase of ED1-positive macrophages (p < 0.05) was observed at 7, 14 and 28 dpi in treated animals compared to untreated, indicative of macrophage stimulation. Less degenerative structures were found in sections distal to the injury in treated animals, seemingly due to a pro-phagocytic effect. Reactive gliosis was significantly (p < 0.05) less pronounced in CM101-treated animals. The presence of GAP43-positive sprouts and neurofilament-positive neurites distal to the lesion in treated animals indicate regrowth of axons crossing the glial scar.


CONCLUSIONS
Treatment with group B-streptococcus exotoxin leads to macrophage stimulation, increased phagocytosis of inhibitory debris, and a less dense reactive gliosis, which in turn allows for regrowth of axons through the glial scar.
Ohlsson
Marcus
M
Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet and Karolinska Hospital, S-171 76 Stockholm, Sweden. marcus.ohlsson@ks.se
Mattsson
Per
P
Wamil
Barbara D
BD
Hellerqvist
Carl G
CG
Svensson
Mikael
M
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D053331:Ectodysplasins; D005098:Exotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D019922:GAP-43 Protein / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009409:Nerve Crush / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects*; D016900:Neurofilament Proteins / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D053331:Ectodysplasins; D005098:Exotoxins; D019922:GAP-43 Protein; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D016900:Neurofilament Proteins; D011135:Polysaccharides, Bacterial; C032263:streptococcal polysaccharide type III group B