title: Bioenergetics of the spinal cord in experimental autoimmune encephalitis of rats.
abstract: BACKGROUND
  Mitochondrial dysregulation is important in axonal damage and demyelination in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). There is however, no evidence in the literature of any study that has examined cellular bioenergetics of the central nervous system (CNS) during the early development and clinical course of EAE. EAE, a rodent model of relapsing/remitting MS, is a CD4(+) T cell-mediated disease of the CNS. We hypothesize that CNS bioenergetics might predict prognosis, and that preserved bioenergetics might underlie the remission from disease. The study aims therefore, to determine whether the clinical history of EAE is influenced by cellular respiration of the CNS in susceptible Dark Agouti (DA) and resistant Albino Oxford (AO) rats.
  
  
  METHODS
  Experimental autoimmune encephalomyelitis was induced by myelin basic protein in complete Freud Adjuvant in the footpads of DA and AO rats. A phosphorescence analyzer that determines cellular respiration was used to monitor oxygen consumption and ATP concentration was measured using the Enliten ATP assay system. Disease pathology was demonstrated by H&E and Luxol fast blue staining of sections of the lumbar regions of the spinal cord. Mitochondrial size in relation to axonal size was determined by electron microscopy. Apoptosis was studied by HPLC measurement of intracellular caspase-3 activity and caspase immunohistochemistry. Role and source of caspase 1 was studied by double immunofluorescence with antibodies for caspase-1, microglia (anti-Iba1) and astrocytes (anti-GFAP).
  
  
  RESULTS
  The cellular respiration of the CNS did not vary between diseased and normal rats. We also demonstrate here, that at the peak of disease, inflammation as shown by caspase-1, produced by activated microglia and infiltrating cells, was significant in susceptible DA rats. The mitochondrial:axonal size ratio did not vary in the different groups although mitochondria were smaller in spinal cords of diseased DA rats. Demyelination, observed only in areas of mononuclear infiltration of the spinal cord of diseased DA rats, was demonstrated by light microscopy and electron microscopy.
  
  
  CONCLUSIONS
  We conclude that EAE at this early stage does not significantly affect CNS cellular respiration and this might underlie the reason for the recovery of diseased rats.
authors.affiliation: Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. mshamsi@uaeu.ac.ae.
authors.forename: Mariam
authors.initials: M
authors.lastname: Al-Shamsi
authors.affiliation: Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. shahin.a@uaeu.ac.ae.
authors.forename: Allen
authors.initials: A
authors.lastname: Shahin
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. marwa_farid@msn.com.
authors.forename: Marwa F
authors.initials: MF
authors.lastname: Ibrahim
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. stariq@uaeu.ac.ae.
authors.forename: Saeed
authors.initials: S
authors.lastname: Tareq
authors.affiliation: Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. asouid@uaeu.ac.ae.
authors.forename: Abdul-Kader
authors.initials: AK
authors.lastname: Souid
authors.affiliation: Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, UAE. ericb@uaeu.ac.ae.
authors.forename: Eric P K
authors.initials: EP
authors.lastname: Mensah-Brown
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D004734:Energy Metabolism; D005620:Freund's Adjuvant; D008159:Lumbar Vertebrae; D008297:Male; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D053142:Mitochondrial Size / Q000502:physiology; D004676:Myelin Basic Protein; D051381:Rats; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: D004676:Myelin Basic Protein; D000255:Adenosine Triphosphate; D005620:Freund's Adjuvant; C505410:Casp3 protein, rat; D053148:Caspase 3; D020170:Caspase 1