Regeneration of adult rat spinal cord is promoted by the soluble KDI domain of gamma1 laminin.
Regeneration in the central nervous system (CNS) of adult mammals is hampered by formation of a glial scar and by proteins released from the myelin sheaths of injured neuronal pathways. Our recent data indicate that the KDI (Lys-Asp-Ile) domain of gamma1 laminin neutralizes both glial- and myelin-derived inhibitory signals and promotes survival and neurite outgrowth of cultured human spinal cord neurons. We show that after complete transection of the adult rat spinal cord, animals receiving onsite infusion of the KDI domain via osmotic mini-pumps recover and are able to sustain their body weights and walk with their hindlimbs. Animals treated with placebo suffer from irreversible hindlimb paralysis. Microscopic and molecular analyses of the spinal cords indicate that the KDI domain reduces tissue damage at the lesion site and enables neurite outgrowth through the injured area to effect functional recovery of the initially paralyzed animals. That the KDI domain enhances regeneration of acute spinal cord injuries in the adult rat suggests that it may be used to promote regeneration of spinal cord injuries in humans.
Wiksten
Markus
M
The Brain Laboratory, Department of Biological and Environmental Sciences (Physiology), 00014 University of Helsinki, Helsinki, Finland.
Väänänen
Antti J
AJ
Liebkind
Ron
R
Liesi
Päivi
P
D000818:Animals; D001522:Behavior, Animal; D007150:Immunohistochemistry / Q000379:methods; D007796:Laminectomy / Q000379:methods; D007797:Laminin / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D007797:Laminin; D016900:Neurofilament Proteins; D010455:Peptides; C089141:laminin gamma 1; C066858:neurofilament protein NF 68; D012701:Serotonin