Lipid peroxidation in brain or spinal cord mitochondria after injury

Abstract

Extensive evidence has demonstrated an important role of oxygen radical formation (i.e. oxidative stress) as a mediator of the secondary injury process that occurs following primary mechanical injury to the brain or spinal cord. The predominant form of oxygen radical-induced oxidative damage that occurs in injured nervous tissue is lipid peroxidation (LP). Much of the oxidative stress in injured nerve cells initially begins in mitochondria via the generation of the reactive nitrogen species peroxynitrite (PN) which then can generate multiple highly reactive free radicals including nitrogen dioxide (•NO2), hydroxyl radical (•OH) and carbonate radical (•CO3). Each can readily induce LP within the phospholipid membranes of the mitochondrion leading to respiratory dysfunction, calcium buffering impairment, mitochondrial permeability transition and cell death. Validation of the role of LP in central nervous system secondary injury has been provided by the mitochondrial and neuroprotective effects of multiple antioxidant agents which are briefly reviewed.

Therapeutic effects of vitamin D3 on motor functions following experimental spinal cord injury

“…SKY sonrası nörolojik hasar 'primer mekanik yaralanma' ile olduğu kadar doku hasarına yol açan hücre ölümü aktivasyon kaskatlarından da (sekonder yaralanma) kaynaklanmaktadır (32). Sekonder omurilik yaralanması; oluşan primer yaralanmanın başlattığı ve yaralanmadan sonraki saatler ve günler içerisinde gelişen bir dizi patofizyolojik sürece bağlı olarak ortaya çıkan hasardır (33)(34)(35). Birçok deneysel çalışma, doza bağlı olarak yaralanmanın ciddiyetiyle değişmekle birlikte omurilik kan akımında azalma ve yaralanmadan sonra zamanla kötüleşen bir omurilik kan akımı azalması olduğunu göstermiştir (36).…”

Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target

“…A short therapeutic window is one significant limitation of the aforementioned indirect mechanisms. Multiple studies have reported near instantaneous increases in ROS production after SCI (Liu et al, 1998Bao and Liu, 2004;Xiong et al, 2007), which means that pharmacological agents would need to be administered immediately to ensure that they are able to act and interfere with the initial "burst" of free radical production that occurs after SCI (Hall, 2011;Bains and Hall, 2012;Hall et al, 2016).…”

“…Although there have been promising preliminary studies investigating the efficacy of NACA, NIM811, Mdivi-1, and mitochondrial-targeted antioxidants, there remains a great deal of work to be done with these compounds and, as is often the case, there is no guarantee that the results observed in animals will translate to humans. Hall et al (2016) suggested that combinatorial therapies could address the obvious deficit in treatment, as pursuing a single facet of the mitochondrial dysfunction-induced damage that occurs after SCI may not be enough to produce effective neuroprotection. An alternate method of targeting multiple aspects of mitochondrial function that has not yet been effectively explored for the treatment of SCI is pharmacological enhancement of mitochondrial biogenesis (MB).…”

“…Development of peroxynitrite is increased after injury due to the increased concentration of superoxide and Ca 21 -induced activation of nitric oxide synthase within the mitochondria (Bringold et al, 2000). Peroxynitrite can also trigger cell membrane lipid peroxidation (LP), protein carbonylation, and tyrosine nitration, damaging and impairing mitochondria and altering neuronal function after SCI (Violi et al, 1999;Sullivan et al, 2007;Hall et al, 2016).…”

“…LP results in additional free radicals, which propagate damage (Hall et al, 2016). LP can occur in blood vessels and neurons, which not only impairs neuronal and vascular integrity but also promotes ischemia and further contributes to secondary neuronal injury (Hall and Springer, 2004).…”