(404) Http failure response for https://api.library.tamu.edu/scholars-discovery/individual/n9999: 404 Not Found
Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats | Academic Article individual record
abstract

Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1's neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain.

author list (cited authors)
Bake, S., Selvamani, A., Cherry, J., & Sohrabji, F.
publication date
2014
published in
PLoS ONE Journal
keywords
  • Cytokines
  • Sex Factors
  • MicroRNAs
  • Female
  • Time Factors
  • Age Factors
  • Disease Models, Animal
  • Proto-Oncogene Proteins C-akt
  • Neuroprotective Agents
  • Signal Transduction
  • Animals
  • Gene Expression Regulation
  • Blood-Brain Barrier
  • Oxidative Stress
  • Inflammation
  • Phosphorylation
  • Stroke
  • Permeability
  • Rats
  • Insulin-Like Growth Factor I
citation count

45