Excitotoxic injury

Other Links Between Chemokines and Excitotoxic Injury Glutamate Release... 

Besides the clear role for chemokines in modulating recruitment of cells into the CNS in HIV infection, and the potential role for chemokines to directly modulate neuronal signaling, recent evidence has suggested a link between CNS chemokine expression and enhancement of excitotoxic injury through enhancement of glutamate... 

This drug is more potent and more selective for fibrin-bound plasminogen than any other known plasminogen activator. Unlike t-PA, desmoteplase is not activated by fibrinogen or (3-amyloid proteins, factors that may exacerbate the risk for ICH. Moreover, desmoteplase inhibits t-PA-induced potentiation of excitotoxic injury. The effect of IV administration of desmoteplase 3-9 hours after symptom onset in stroke patients who demonstrate a mismatch on PWI/DWI MRI is currently being investigated. ... 

However, overactivation of AMPA or KA receptors can also lead to intracellular Ca2+ overload and neurodegeneration. This maybe especially true under conditions where NMDA-receptor activity is reduced by extracellular acidity or a buildup of extracellular Zn2+ [ 12]. It is also true with respect to specific neuronal subpopulations that express AMPA-sensitive Ca2+ channels (see Ch. 15). G-protein-linked metabotropic glutamate receptors (mGluRs) appear not to mediate excitotoxicity directly but, rather, to modify the degree of excitotoxic injury. 

YuZ., Zhou D., Bruce-Keller A. J., Kindy M. S., and Mattson M. P. (1999). Lack of the p50 subunit of nuclear factor-icB increases the vulnerability of hippocampal neurons to excitotoxic injury. J. Neurosci. 19 8856-8865. 

As with CuZnSOD, CA1 and CA3 had decreased immunoreactivity to MnSOD, but intense immunoreactivity was observed in astrocytes at 3 and 7 days after kainate injection. (Kim et al., 2000a,b). The early loss of both CuZu SOD and Mn SOD are possible causes of increased oxidative stress after kainate-induced excitotoxic injury. 

Huang E., Ong W. Y., Go M. L., and Garey L. J. (2005). Heme oxygenase-1 activity after excitotoxic injury immunohistochemical localization of bilirubin in neurons and astrocytes and deleterious effects of heme oxygenase inhibition on neuronal survival after kainate treatment. J. Neurosci. Res. 80 268-278. 

Regan R. F. and Guo Y. P. (1999). Potentiation of excitotoxic injury by high concentrations of extracellular reduced glutathione. Neuroscience 91 463 170. 

Wang X. S., Ong W. Y., and Connor J. R. (2002b). Increase in ferric and ferrous iron in the rat hippocampus with time after kainate-induced excitotoxic injury. Exp. Brain Res. 143 137-148. 

Dijkhuizen RM, de Graaf RA, Tulleken KA, Nicolay K (1999) Changes in the diffusion of water and intracellular metabolites after excitotoxic injury and global ischemia in neonatal rat brain. J Cereb Blood Flow Metab 19 341-349... 

Stefanis L, Burke RE (1996) Transneuronal degeneration in substantia nigra pars reticulata following striatal excitotoxic injury in adult rat time-course, distribution, and morphology of cell death. Neuroscience 74(4) 997-1008. 

Quinolinate has been known for more than 25 years to produce HD-like pathology in rodents (e.g., Beal et al., 1986). Thus, it has been suggested that the genetic defect in HD may result in heightened neuronal susceptibility to excitotoxic injury. Guidetti et al. (2004) have shown that the levels of quinolinate (an endogenous neuroactive metabolite of the kynurenine pathway of tryptophan metabolism) and... 

Parathath, S., Parathath, S., Tsirka, S. (2006). Nitric oxide mediates neurodegeneration and breakdown of the blood brain barrier in tPA-dependent excitotoxic injury in mice. J. Cell Sci. 119 339 9. 

Piehn JH, MUler RJ (1996) Opposite effects of TGF-beta 1 on rapidly- and slowly-triggered excitotoxic injury. Neuropharmacology 35 249-256. 

DiFiglia M (1990) Excitotoxic injury of the neostriatum a model for Huntington s disease. Trends Neurosci 13 286-289. 

Duan W, Guo Z, Mattson MP (2001) Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury. J Mol Neurosci 16 1-12. 

D Aldin CG, Ruel J, Assie R, Pujol R, Fuel JL (1997) Implication of NMDA type glutamate receptors in neural regeneration and neoformation of synapses after excitotoxic injury in the guinea pig cochlea. Int J Dev Neurosci 75 619-629. 

Huang PP, Esquenazi S, Le Roux PD. Cerebral cortical neuron apoptosis after mild excitotoxic injury in vitro Different roles of mesencephalic and cortical astrocytes. Neurosurgery 1999 45 1413-1422. 

Mattson, M.P., Cheng, B. and Smithswintosky, V.L. (1993b) Mechanisms of neurotrophic factor protection against cal-cium-and free radical-mediated excitotoxic injury - implications for treating neurodegenerative disorders. Exp. Neurol. 124 89-95. 

The research described in this chapter is based on the hypothesis that a causal relationship exists between excitotoxic injury and the generation of ROS, RNS, and lipid peroxidation, Since anticholinesterase agents primarily cause excitotoxicity in brain and skeletal muscle, this chapter describes the correlation between changes in nitric... 

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