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

Exp Neurol. 2005 Jun;193(2):291-311. doi: 10.1016/j.expneurol.2005.01.004.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

  • 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