Soluble KDI domain of gamma1 laminin protects adult hippocampus from excitotoxicity of kainic acid.
Recent data indicate that the soluble KDI domain of gamma1 laminin promotes survival and neurite outgrowth of human central neurons in vitro (Liebkind et al.[2003] J Neurosci Res 73:637-643), and seems to neutralize both glia- and myelin-derived signals that hamper regeneration in the central nervous system (CNS) of adult mammals. We show that damage of adult rat neocortical and hippocampal areas by a stereotaxic injection of kainic acid (KA) is prevented by a preceding injection of the soluble KDI domain. In the presence of the KDI domain, both neocortical and hippocampal areas show extensive gliosis but have viable neurons and glial cells, which are absent and the areas fully destroyed after injection of KA alone. This result indicates that the KDI domain of the gamma1 laminin protects the CNS against excitotoxic insults and promotes survival of both neurons and glial cells. The KDI domain may thus be a potential drug to prevent CNS damage induced by neurodegenerative disorders, mechanical injury, or ischemia.
The Brain Laboratory, Department of Biological and Environmental Sciences (Physiology), 00014 University of Helsinki, Helsinki, Finland.
Markus
M
Wiksten
Antti
A
Väänänen
Ron
R
Liebkind
Pekka
P
Rauhala
Päivi
P
Liesi
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004347:Drug Interactions; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D007608:Kainic Acid; D007797:Laminin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods; D013238:Stereotaxic Techniques
D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; C121346:laminin 1; C089141:laminin gamma 1; D007608:Kainic Acid