Induced neuronal oxidative injury

Gupta, R.C., Milatovic, S., Dettbam, W-D., Aschner, M., Milatovic, D. (2007). Neuronal oxidative injury and dendritic damage induced by carbofuran protection by memantine. Toxicol. Appl. Pharmacol. 219 97-105. 

Zhu Y, Jones G et al (2005) Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root ganglia pathogenic effects of STAT-1 and inducible nitric oxide synthase. J Immunol 175(2) 1118-1126... 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

Taken together, these results showed that EGb can prevent ischemia-induced Na,K-AIPase injury, and suppress hypoxia- and ECS-induced membrane phospholipid breakdown in the brain, and bilobalide might be associated with its protective action. In addition, EGb reduces AA-induced neuronal damage as a consequence of the increase in reincorporation of AA Therefore, these mechanisms might provide a possible explanation for neuroprotective properties of EGb and bilobalide against oxidative damage. 

Ong W. Y., Goh E. W. S., Lu X. R., Farooqui A. A., Patel S. C., and Halliwell B. (2003). Increase in cholesterol and cholesterol oxidation products, and role of cholesterol oxidation products in kainate-induced neuronal injury. Brain Path. 13 250-262. 

Toborek M., Malecki A., Garrido R., Mattson M. P., Hennig B., and Young B. (1999). Arachidonic acid-induced oxidative injury to cultured spinal cord neurons. J. Neurochem. 73 684-692. 

In conclusion, the data demonstrated that synergistic mechanisms of cellular disruption caused by anticholinesterase agents led to cellular dysfunction and neurodegeneration. It has also been demonstrated that preventing CF-induced neuronal hyperactivity by pretreatment with MEM and atropine blocks pathways associated with oxidative damage in rat brain. The documented abihty of MEM therapy to reduce free radical generation and lipid peroxidation, prevent HEPs and attenuate the morphological injury provides further support for the role of ROS and RNS in anticholinesterase-induced seizures. 

Cazevieille, C., Muller, A., Meynier, F., and Bonne, C. (1993). Superoxide and nitric oxide cooperation in hypoxia/reoxygenation-induced neuron injury. Free Radical Biol. Med. 14, 389-395. 

Fig. 2.5 Diagram showing effect of oxidative and nitrosative stress on neuronal injury. Plasma membrane (PM) Af-methyl-D-aspartate receptor (NMDA-R) glutamate (Glu) phosphatidylcholine (PtdCho) lyso-phosphatidylcholine (lyso-PtdCho) cytosolic phospholipase A2 (CPLA2) secretory phosphohpase A2 (SPLA2) cyclooxygenase (COX-2) arachidonic acid (ARA) reactive oxygen species (ROS) nuclear factor kappaB (NF-kB) nuclear factor kappaB response element (NF-kB-RE) inhibitory subunit of NFkB (IkB) inducible nitric oxide synthase (iNOS) perox-ynitrite (ONOO ) Superoxide ( O2) matrix metalloproteinases (MMPs) vascular cell adhesion molecule-1 (VCAM-1) poly(ADP-ribose) polymerase (PARP) nicotinamide (Nam) nicotineunide adenine dinucleotide (NAD) positive sign (+) represents upregulation...

---