Chronic relapsing experimental autoimmune encephalomyelitis: Effects of insulin-like growth factor-I treatment on clinical deficits, lesion severity, glial responses, and blood brain barrier defects

W. Li, L. Quigley, D. L. Yao, L. D. Hudson, M. Brenner, B. J. Zhang, S. Brocke, H. F. McFarland, H. Def Webster

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic relapsing experimental autoimmune encephalomyelitis (crEAE), a model for multiple sclerosis, was used to test 2 regimens of insulin-like growth factor-I (IGF-I) treatment. We induced crEAE by injecting 3x107 myelin basic protein-(MBP) sensitized lymph node cells into adult female SJL/J mice. Fifty-one mice, divided randomly into 4 groups, were used in the first trial. Two groups received IGF-I (a gift of Cephalon, Inc.) 0.6 mg/kg/d subcutaneously from day 7 to day 16 and the other two groups received placebo injections. IGF-I treatment reduced clinical deficits during the first attack and during 2 subsequent relapses. Image analysis of immunostained and histological sections showed that IGF-I treatment reduced BBB defects and both the numbers and sizes of inflammatory, demyelinating, and demyelinated lesions. Twelve mice that had recovered from their first attack were used in our second trial to evaluate possible adverse effects of prolonged treatment with a higher dose of IGF-I. Six received 1.2 mg/kg/d for 6 weeks (days 19- 63). No adverse effects of IGF-I treatment were identified. The eyes, hearts, livers, and kidneys of IGF-I-treated mice were normal histologically and their spleen also appeared normal except for mild to moderate microscopic increases in lymphopoesis. Our results suggest that prolonged IGF-I treatment is well tolerated and that the anti-inflammatory effects of IGF-I have a major role in reducing clinical deficits and lesion severity in crEAE. These effects, if present in multiple sclerosis, may benefit patients with this disease.

Original languageEnglish (US)
Pages (from-to)426-438
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume57
Issue number5
StatePublished - May 1998
Externally publishedYes

Keywords

  • Demyelination
  • Growth factor
  • Inflammation
  • Multiple sclerosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

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