Growth-associated gene expression after stroke: evidence for a growth-promoting region in peri-infarct cortex.

Abstract

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.

• Authors: S Thomas Carmichael, Ivonne Archibeque, Linslee Luke, Tim Nolan, Janneth Momiy, Songlin Li
• Journal: Experimental neurology (Exp Neurol) Vol. 193 Issue 2 Pg. 291-311 (Jun 2005) ISSN: 0014-4886 [Print] United States
• PMID: 15869933 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Acan protein, rat
• Aggrecans
• Chondroitin Sulfate Proteoglycans
• Extracellular Matrix Proteins
• Lectins, C-Type
• Nerve Growth Factors
• Nerve Tissue Proteins
• Proteoglycans
• RNA, Messenger
• Vcan protein, rat
• Versicans
• Chondroitin Sulfates
• Ptprz1 protein, rat
• Receptor-Like Protein Tyrosine Phosphatases, Class 5

Topics

• Aggrecans
• Animals
• Brain Infarction (etiology, metabolism)
• Cerebral Cortex (metabolism, pathology)
• Chondroitin Sulfate Proteoglycans (genetics, metabolism)
• Chondroitin Sulfates (genetics, metabolism)
• Disease Models, Animal
• Extracellular Matrix Proteins (genetics, metabolism)
• Gene Expression (physiology)
• Gene Expression Regulation
• Immunohistochemistry (methods)
• In Situ Hybridization (methods)
• Lectins, C-Type
• Male
• Nerve Growth Factors (genetics, metabolism)
• Nerve Tissue Proteins (genetics, metabolism)
• Proteoglycans (genetics, metabolism)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Inbred F344
• Receptor-Like Protein Tyrosine Phosphatases, Class 5
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Stroke (complications, metabolism)
• Time Factors
• Versicans