The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats

PLoS One. 2013 May 22;8(5):e64015. doi: 10.1371/journal.pone.0064015. Print 2013.

Abstract

Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I) injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and these effects could contribute to neuroprotection and improve motor function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Injections, Intramuscular / methods
  • Insulin-Like Growth Factor I / administration & dosage*
  • Male
  • Motor Cortex / drug effects
  • Motor Cortex / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism

Substances

  • Neuroprotective Agents
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt

Grants and funding

This article was supported by grant NSC95-2314-B-010-041-MY3 from the National Science Council of the Republic of China. The funder has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.