Delayed excitotoxicity

In order to refine therapeutic regimes and thus prevent chemical warfare agent-induced excitatory neurodegeneration in exposed individuals (Figure 5.4), a more comprehensive characterization of the destructive signal-transduction mechanisms and intracellular enzymatic cascades associated with glutamate receptor mediated delayed excitotoxicity (PCD) is needed. Accordingly, the refinement of therapeutic... 

GMl, an agent that prevents delayed excitotoxic cell damage in culture (DeErasquin et al., 1990), attenuates the motor symptoms in primates treated with MPTP (Schneider et al., 1992). In the MPTP model, interest has also centered on the ability of... 

O Hearn E, Zhang P, Molliver ME. (1995). Excitotoxic insult due to ibogaine leads to delayed induction of neuronal NOS in Purkinje cells. Neuroreport. 6(12) 1611-16. 

Pang Z, Geddes JW (1997) Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid acute excitotoxic necrosis and delayed apoptosis. J Neurosci 17 3064-3073 Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94 79-100... 

The proinflammatory effects of HMGBl were studied in the postischemic brain of rats. Ischemia injury in the brain proceeds with excitotoxicity-induced acute neuronal cell death in the ischemic core, followed by delayed damage to the penumbra (Lee et al., 2000b). It was observed that HMGBl was immediately released into... 

M., Krohn, A.J., Bauerbach, E., Krieglstein, J., Prehn, J.H. (2000). Delayed mitochondrial dysfunction in excitotoxic neuron death cytochrome c release and a secondary increase in superoxide production. J. Neurosci. 20 5715-23. 

Skaper SD, Buriani A, Dal Toso R, Petrelli L, Romanello S, Facci L, Leon A (1996) The ALlAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc Natl Acad Sci USA 93 3984-3989... 

Biapigenin (153) is neuroprotective against excitotoxic insults. The observed neuroprotection was correlated with prevention of delayed calcium deregulation and with the maintenance of mitochondrial transmembrane electric potential. Biapigenin was also able to significantly affect mitochondrial bioenergetics and decreased the capacity of mitochondria to accumulate calcium. 

Fig. 1.2 Putative cascade of damaging events in focal cerebral ischemia. Very early after the onset of the focal perfusion deficit, excitotoxic mechanisms can damage neurones and glia lethaUy. In addition, excitotoxicity triggers a number of events that can further contribute to the demise of the tissue. Such events include peri-infarct depolarizations and the more-delayed mechanisms of inflammation and programmed cell death. The x-axis reflects the evolution of the cascade over time, while the y-axis aims to illustrate the impact of each element of the cascade on final outcome (courtesy of Dimagl et al. 1999)...

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