Affiliations: Department of Clinical Neuroscience, Section of
Neurosurgery, Karolinska Institutet and Karolinska Hospital, S-171 76
Stockholm, Sweden | Department of Biochemistry, Vanderbilt University, TN
37232-0146, USA
Note: [] Corresponding author: Marcus Ohlsson, M.D., Ph.D., Department of
Neurosurgery, Karolinska Hospital, 171 76 Stockholm, Sweden. Tel.: +46 8 5177
0000 operator; Fax: +46 8 5177 1778; E-mail: [email protected]
Abstract: Purpose: 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 μm/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. Conclusion: 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.
