Oxidative injury in multiple sclerosis cerebellar grey matter

Kevin Kemp, Juliana Redondo, Kelly Hares, Claire Rice, Neil Scolding, Alastair Wilkins

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
355 Downloads (Pure)

Abstract

Abstract Cerebellar dysfunction is a significant contributor to disability in multiple sclerosis (MS). Both white matter (WM) and grey matter (GM) injury occurs within MS cerebellum and, within GM, demyelination, inflammatory cell infiltration and neuronal injury contribute to on-going pathology. The precise nature of cerebellar GM injury is, however, unknown. Oxidative stress pathways with ultimate lipid peroxidation and cell membrane injury occur extensively in MS and the purpose of this study was to investigate these processes in MS cerebellar GM. Post-mortem human cerebellar GM from MS and control subjects was analysed immunohistochemically, followed by semi-quantitative analysis of markers of cellular injury, lipid peroxidation and anti-oxidant enzyme expression. We have shown evidence for reduction in myelin and neuronal markers in MS GM, coupled to an increase in expression of a microglial marker. We also show that the lipid peroxidation product 4-hydroxynonenal co-localises with myelin and its levels negatively correlate to myelin basic protein levels. Furthermore, superoxide dismutase (SOD1 and 2) enzymes, localised within cerebellar neurons, are up-regulated, yet the activation of subsequent enzymes responsible for the detoxification of hydrogen peroxide, catalase and glutathione peroxidase are relatively deficient. These studies provide evidence for oxidative injury in MS cerebellar GM and further help define disease mechanisms within the MS brain.
Original languageEnglish
Pages (from-to)452-460
Number of pages9
JournalBrain Research
Volume1642
Early online date14 Apr 2016
DOIs
Publication statusPublished - 1 Jul 2016

Keywords

  • Multiple sclerosis
  • Cerebellum
  • Grey matter
  • Oxidative stress
  • Peroxidation
  • Anti-oxidants

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