title: Coadministration of epidermal growth factor and growth hormone releasing peptide-6 improves clinical recovery in experimental autoimmune encephalitis.
abstract: OBJECTIVE
  Multiple sclerosis is a complex and devastating autoimmune disease of the central nervous system. Up to now, a constellation of candidate drugs have been evaluated with no major success. Experimental Autoimmune Encephalitis (EAE) is the animal counterpart that reproduces critical features of the human MS process. The aim of the present work is to study a possible therapeutic effect of epidermal growth factor (EGF) and growth hormone releasing peptide-6 (GHRP(6)) coadministration in mild and severe EAE.
  
  
  METHODS
  Mild and severe forms of EAE were generated immunizing rats and mice with xenogeneic spinal cord homogenate and with the encephalitogenic peptide MOG(p35-35), respectively. EGF and GHRP(6) alone or combined were administered in therapeutic and prophylactic schedules. A clinical score was established to follow-up the animals during the disease period. Malondialdehyde (MDA) serum concentration and insulin like growth factor-1 (IGF-1) relative level from brain tissue were determined.
  
  
  RESULTS
  Only the combined EGF+GHRP(6) therapy reduced the clinical score in mild as well in severe EAE forms. The combination also improved the survival rate in nearly 100% of the severe EAE animals. In addition to these effects, there was an increase in the brain IGF-1 transcript and a decrease of serum MDA.
  
  
  CONCLUSIONS
  EGF+GHRP(6) proved to be effective in improving the natural course of both mild and severe EAE. Accordingly, the treatment reduces inflammatory infiltration and microvascular damage, which may be associated to the attenuation of the lipid peroxidation process and the transcriptional enhancement of IGF-1, a major pro-survival factor for brain cells.
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cubanacan, Playa, Havana, Cuba. diana.garcia@cigb.edu.cu
authors.forename: Diana García
authors.initials: DG
authors.lastname: del Barco
authors.forename: Enrique
authors.initials: E
authors.lastname: Montero
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Coro-Antich
authors.forename: Enma
authors.initials: E
authors.lastname: Brown
authors.forename: José
authors.initials: J
authors.lastname: Suarez-Alba
authors.forename: Laura
authors.initials: L
authors.lastname: Lopez
authors.forename: Nelvys
authors.initials: N
authors.lastname: Subirós
authors.forename: Jorge
authors.initials: J
authors.lastname: Berlanga
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006728:Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D006728:Hormones; D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D008315:Malondialdehyde; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I