Neuronal necrosis

Fatal encephalopathy Morphological findings cerebral edema, endothelial hypertrophy and hyperplasia, perivascular glial proliferation injury secondary to cerebral vasculopathy ischemic disorders cell necrosis, neuronal loss in isocortex and basal ganglia Pentschew (1965), Popoff etal. (1963)... 

There is an increasing body of evidence that supports an apoptosis-necrosis cell death continuum. In this continuum, neuronal death can result from varying contributions of coexisting apoptotic and necrotic mechanisms [2]. Therefore the distinct designations... 

Fig. 4.4 Simplified hypothesis of the mechanism of gpI20-induced dorsal root gangUon (DRG) neurotoxicity. CXCR4 binding on Schwann cells by SDF-Ia or gpI20 results in the release of RANTES, which induces tumor necrosis factor (TNF)-a production by DRG neurons, and subsequent TNFRl-mediated neurotoxicity in an autocrine/paracrine fashion. Reproduced with permission of John Wiley Sons, Inc. (Keswani et al. 2003b)...

S3fntichaki P, Tavemarakis N. The biochemistry of neuronal necrosis rogue biology Nat Rev Neurosci 2003 4 672-684. 

During ischaemia, NOS is activated by calcium influx or by cytokines like tumour necrosis factor (TNF) or by lipopolysaccharide (LPS) and NO is produced in excess. It has been proposed that the excitotoxic effect of glutamate, which contributes to ischaemia-induced neuronal damage, is mediated by increased production of NO via a chain of events that includes increases in intracellular calcium (via glutamate activation of NMDA receptors), calcium activation of NOS, production of NO and peroxynitrite, and induction of lipid peroxidation. In fact, N-nitro-L-atginine, a selective inhibitor of NOS, has been shown to prevent glutamate-induced neurotoxicity in cortical cell cultures (Dawson rf /., 1991). 

Fas ligand and interleukin-ip), the neurotransmitter glutamate and thrombin. Like tumor necrosis factor (TNF) receptors, Fas is coupled to downstream death effector proteins that ultimately induce caspase activation (Ch. 22). Fas and TNF receptors recruit proteins called FADD and TRADD respectively FADD and TRADD then activate caspase-8, which, in turn, activates caspase-3 (Fig. 35-4). Calcium ion influx mediates neuronal apoptosis induced by glutamate receptor activation calcium induces mitochondrial membrane permeability transition pore opening, release of cytochrome c and caspase activation. Interestingly, in the absence of neurotrophic factors some neurotrophic factor receptors can activate apoptotic cascades, the low-affinity NGF receptor being one example of such a death receptor mechanism [23],... 

Neuronal PCD with features of necrosis was reported in studies of naturally occurring motor neuron death in which the cells exhibited dilation of ER, Golgi and nuclear membranes but not condensation of chromatin. A similar... 

In regards to necrosis, it is clear that the old adage an ounce of prevention is worth a pound of cure applies. Agents that stabilize ion homeostasis have proved to be effective in preventing necrosis in cell culture studies. For example, drugs that activate plasma membrane potassium ion channels or chloride ion channels can prevent membrane depolarization and so inhibit sodium and calcium ion influx. Agents that prevent large sustained increases in intracellular free calcium levels can also prevent neuronal... 

---