Complement activation following optic nerve crush in the adult rat.
Activation of the complement cascade following peripheral nerve axotomy and following traumatic brain injury has been demonstrated in previous studies. This study investigates the temporal pattern of microglia/macrophages and complement activation following axotomy of sensory CNS neurons, using a standardized experimental crush injury of the optic nerve in adult rats. Numerous ED1-labeled macrophages were found at the lesion site and distal to the injury at 7 days post injury (dpi). Complement C3-mRNA was upregulated 2-28 days post lesion, indicating local synthesis of complement in the optic nerve. Furthermore, increased immunoreactivity (IR) for the end product of the complement cascade, the membrane attack complex (MAC), was detected along disintegrating axons co-labeled with anti-neurofilament distal to the injury. Double-labeling for microglia show MAC-immunoreactivity expressed in their immediate vicinity, indicating a key role of microglia/macrophages in complement activation. The complement regulator Clusterin was upregulated in astrocytes at the lesion site as well as in the distal portion of the injured optic nerve, suggesting activation of a defense response to endogenous complement attack. A crush injury of the optic nerve leads to complement activation at the site of lesion and along the distal portion of the nerve, as well as upregulation of the complement inhibitor Clusterin at least in astrocytes. Reactive microglial cells seem to have a key role in complement activation as a local source of C3. We suggest that the balance between complement activation and their regulators may have impact on axonal degeneration following optic nerve injury.
Ohlsson
Marcus
M
Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet and Hospital, 171-76 Stockholm, Sweden. marcus.ohlsson@ks.se
Bellander
Bo-Michael
BM
Langmoen
Iver A
IA
Svensson
Mikael
M
D000818:Animals; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000096:biosynthesis; D005260:Female; D009409:Nerve Crush / Q000379:methods*; D020221:Optic Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D003176:Complement C3; D012333:RNA, Messenger