Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy?
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Mitochondrial dysfunction and oxidative stress contribute to several neurologic disorders and have recently been implicated in acquired epilepsies such as temporal lobe epilepsy (TLE). Acquired epilepsy is typically initiated by a brain injury followed by a “latent period” whereby molecular, biochemical and other cellular alterations occur in the brain leading to chronic epilepsy. Mitochondrial dysfunction and oxidative stress are emerging as factors that not only occur acutely as a result of precipitating injuries such as status epilepticus (SE), but may also contribute to epileptogenesis and chronic epilepsy. Mitochondria are the primary site of reactive oxygen species (ROS) making them uniquely vulnerable to oxidative damage that may affect neuronal excitability and seizure susceptibility. This mini-review provides an overview of evidence suggesting the role of mitochondrial dysfunction and oxidative stress as acute consequences of injuries that are known to incite chronic epilepsy and their involvement in the chronic stages of acquired epilepsy.
KeywordsEpilepsy Mitochondria Oxidative stress
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- Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC (2004) Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Lancet 363:28–37CrossRefGoogle Scholar
- Hinerfeld D, Traini MD, Weinberger RP, Cochran B, Doctrow SR, Harry J, Melov S (2004) Endogenous mitochondrial oxidative stress: neurodegeneration, proteomic analysis, specific respiratory chain defects, and efficacious antioxidant therapy in superoxide dismutase 2 null mice. J Neurochem 88:657–667CrossRefGoogle Scholar
- Mathern GW, Mendoza D, Lozada A, Pretorius JK, Dehnes Y, Danbolt NC, Nelson N, Leite JP, Chimelli L, Born DE, Sakamoto AC, Assirati JA, Fried I, Peacock WJ, Ojemann GA, Adelson PD (1999) Hippocampal GABA and glutamate transporter immunoreactivity in patients with temporal lobe epilepsy. Neurology 52:453–472Google Scholar
- Melov S, Doctrow SR, Schneider JA, Haberson J, Patel M, Coskun PE, Huffman K, Wallace DC, Malfroy B (2001) Lifespan extension and rescue of spongiform encephalopathy in superoxide dismutase 2 nullizygous mice treated with superoxide dismutase-catalase mimetics. J Neurosci 21:8348–8353Google Scholar
- Mueller SG, Trabesinger AH, Boesiger P, Wieser HG (2001) Brain glutathione levels in patients with epilepsy measured by in vivo (1)H-MRS. Neurology 57:1422–1427Google Scholar
- Mustafa AG, Singh IN, Wang J, Carrico KM, Hall ED (2010) Mitochondrial protection after traumatic brain injury by scavenging lipid peroxyl radicals. J Neurochem 114:271–280Google Scholar
- Patel M, Liang LP, Hou H, Williams BB, Kmiec M, Swartz HM, Fessel JP, Roberts LJ 2nd (2008) Seizure-induced formation of isofurans: novel products of lipid peroxidation whose formation is positively modulated by oxygen tension. J Neurochem 104:264–270Google Scholar
- Reed DJ, Savage MK (1995) Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status. Biochim Biophys Acta 1271:43–50Google Scholar
- Schwarzbold ML, Rial D, De Bem TD, Machado DG, Cunha MP, Dos Santos AA, Dos Santos DB, Figueiredo CP, Farina M, Goldfeder EM, Rodrigues AL, Prediger RD, Walz R (2010) Effects of traumatic brain injury of different severity on emotional, cognitive and oxidative stress-related parameters in mice. J Neurotrauma 10:1883–93Google Scholar
- van der Hel WS, Notenboom RG, Bos IW, van Rijen PC, van Veelen CW, de Graan PN (2005) Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology 64:326–333Google Scholar