Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex.
Stroke induces axonal sprouting in peri-infarct cortex. A set of growth-associated genes important in axonal sprouting in peripheral nervous system regeneration and cortical development has recently been defined. The expression profiles of these growth-associated genes were defined during the post-stroke axonal sprouting response using a model of stroke in barrel field cortex. Stroke induces sequential waves of neuronal growth-promoting genes during the sprouting response: an early expression peak (SPRR1), a mid expression peak (p21, Ta1 tubulin, L1, MARCKS), a late peak (SCG10, SCLIP), and an early/sustained pattern (GAP43, CAP23, c-jun). These expression peaks correspond to specific time points in the sprouting response. The expression of the growth-inhibiting chondroitin sulfate proteoglycans aggrecan, brevican, versican, and phosphacan are induced late in the sprouting process; except neurocan, which is increased during the peak of the growth-promoting gene expression. The developmentally associated growth inhibitors ephrin-A5, ephB1, semaphorin IIIa, and neuropilin 1 are also induced in the early phases of the sprouting response. At the cellular level, chondroitin sulfate proteoglycans, in the form of peri-neuronal nets, are reduced in the region of axonal sprouting, during the peak of growth-promoting gene expression. These results identify a unique profile of growth-promoting gene expression in adult cortex after stroke, the inhibitory molecules that are present during the sprouting response, and a region in which growth-promoting genes are increased, growth-inhibitory proteins are diminished and axonal sprouting occurs. This region may be a growth-promoting zone after stroke.
Carmichael
S Thomas
ST
Department of Neurology, Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095, USA. scarmichael@mednet.ucla.edu
Archibeque
Ivonne
I
Luke
Linslee
L
Nolan
Tim
T
Momiy
Janneth
J
Li
Songlin
S
D053674:Aggrecans; D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism; D002809:Chondroitin Sulfates / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D037181:Lectins, C-Type; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020521:Stroke / Q000150:complications / Q000378:metabolism*; D013997:Time Factors; D053675:Versicans
C508321:Acan protein, rat; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C508324:Vcan protein, rat; D053675:Versicans; D002809:Chondroitin Sulfates; C516897:Ptprz1 protein, rat; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5