Neurons excitotoxicity

Neuronal excitotoxicity AEA levels are elevated in the hippocampus of mice treated with kainic acid. 2-AG levels are elevated in rats treated with pilocarpine These are two animal models of epileptic seizures, where the endocannabinoids play an anti-convulsant and protective function Inhibitors of cellular re-uptake... 

The proposal that NO or its reactant products mediate toxicity in the brain remains controversial in part because of the use of non-selective agents such as those listed above that block NO formation in neuronal, glial, and vascular compartments. Nevertheless, a major area of research has been into the potential role of NO in neuronal excitotoxicity. Functional deficits following cerebral ischaemia are consistently reduced by blockers of NOS and in mutant mice deficient in NOS activity, infarct volumes were significantly smaller one to three days after cerebral artery occlusion, and the neurological deficits were less than those in normal mice. Changes in blood flow or vascular anatomy did not account for these differences. By contrast, infarct size in the mutant became larger... 

It is well known that prolonged NMDA glutamate receptor activation results in degeneration of neurons (excitotoxicity). This has been attributed to a large increase in calcium influx, which activates the calmodulin-dependent NOS-1 and leads to sustained elevation of nitric oxide concentrations. The increase in neurodegeneration caused by excitatory amino acids may be due to enhanced oxygen radical formation since superoxide dismutase has a beneficial effect in... 

Excitotoxicity is the over-activity of the glutamatergic system responsible for the large number of dead neurons observed after ischemia (stroke) or epileptic seizures. This neuronal death is due to an overexcitation of the neurons and the massive Ca2+ entry... 

Findings obtained from experimental studies suggest that induction of iNOS mediates inflammatory or ischemic brain damage and that excessively activated nNOS under excitotoxic or ischemic conditions produces NO that is toxic to surrounding neurons. Selective inhibition of iNOS or nNOS may be neuroprotec-tive. This is also the case in glaucoma and diabetic... 

Lowenstein, D.H., Chan, P.H., Miles, M.F. (1991). The stress protein response in cultured neurons Characterization and evidence for a protective role in excitotoxicity. Neuron 7, 1053-1060. 

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... 

Chapman GA, Moores K, Harrison D, Campbell CA, Stewart BR, Strijbos PJ (2000) Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J Neurosci 20 RC87... 

HIV proteins can also disrupt ion homeostasis in astrocytes, which compromises neuronal function (Pulliam et al. 1993 Benos et al. 1994a, b Holden et al. 1999). Intact HIV-1 virions or gpl20 also markedly inhibit glutamate uptake by astrocytes and cause reductions in excitatory amino acid transporter-2 (EAAT2) mRNA and protein levels (Wang et al. 2003). The inability of astrocytes to buffer extracellular glutamate is likely to decrease the excitotoxic threshold of bystander neurons. 

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