Clinical treatments for mitochondrial dysfunctions after brain injury

Amedeo Merenda, Ross Bullock

Research output: Contribution to journalReview article

37 Scopus citations

Abstract

Purpose of review: This review provides a comprehensive look at the evidence supporting the role of mitochondrial dysfunction in promoting neuronal death after acute brain injury, and critically discusses the most recent proposed therapies that could limit the deleterious effects of such a dysfunction on neurological outcome. Recent findings: Following acute brain injury, disruption of calcium homeostasis, overproduction of reactive oxygen species, and opening of the mitochondrial permeability transition pore, are key factors in promoting mitochondrial dysfunction, with ensuing activation of either necrotic or apoptotic cell death pathways. Growing interest has been focused on developing new therapeutic strategies able to oppose these mechanisms. Several pharmacological agents are currently under investigation, including novel calcium channel blockers and antioxidants, uncoupling proteins and mitochondrial permeability transition pore inhibitors. Although a 'magic bullet' has not yet been identified, the results of both preclinical and clinical studies are encouraging. Summary: Therapeutic interventions directly targeting processes and mechanisms responsible for mitochondrial dysfunction, may offer neuroprotection in brain-injured patients. The multifactorial cause of mitochondrial dysfunction suggests, however, the need for further studies aimed at clarifying optimal dose and time for drug administration, as well as the logical combination/sequence of those approaches that may ultimately achieve improvement in neurological outcome.

Original languageEnglish (US)
Pages (from-to)90-96
Number of pages7
JournalCurrent Opinion in Critical Care
Volume12
Issue number2
DOIs
StatePublished - Apr 1 2006

Keywords

  • Brain injury
  • Cyclosporin-A
  • Mitochondrial dysfunction
  • Mitochondrial permeability transition pore
  • Reactive oxygen species

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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