Neuronal death necrosis

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... 

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... 

FIGURE 1 — 18. Neuronal death can occur by either necrosis or apoptosis. Necrosis is analogous to neuronal assassination, in which neurons explode and cause an inflammatory reaction after being destroyed by poisons, suffocation, or toxins such as glutamate. On the other hand, apoptosis is akin to neuronal suicide and results when the genetic machinery is activated to cause the neuron to literally fade away without causing the molecular mess of necrosis. 

New D. R., Maggirwar S. B., Epstein L. G., Dewhurst S., and Gelbard H. A. (1998). HIV-1 Tat induces neuronal death via tumor necrosis factor-a and activation of non-A-methyl-D-aspartate receptors by a NFfcB-independent mechanism. J. Biol. Chem. 273 17852-17858. 

Interplay among excitotoxicity, oxidative stress, and neuroinflammation facilitates neuronal death via apoptosis as well as necrosis (Nicotera and Lipton, 1999 Sastry and Rao, 2000 Farooqui et al., 2004). In neurons, intracellular energy levels and mitochondrial function are rapidly compromised in necrosis, but not in apoptosis, suggesting that the ATP level is a prominent factor in determining the neurochemical events associated with apoptotic and necrotic neural cell death (Nicotera and Leist, 1997 Liu et al., 2001). Apoptosis and necrosis represent the extreme ends of the spectrum of mechanisms for neural cell death (Williamson and Schlegel, 2002 Leist and Nicotera, 1998 Nicotera and Lipton, 1999). 

Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., and Nicotera, P., 1995, Glutamate-induced neuronal death a succession of necrosis or apoptosis depending on... 

Figure 14.9. Summary of the role of glutamate, p-amyloid and pro-inflammatory cytokines such as tumour necrosis factor (TNF) in the production of reactive oxygen species leading to neuronal death.

Various studies have been conducted on excitatory amino acids and their receptors to explain the neuronal cell death (necrosis) after cerebral ischemia. The mechanism of ischemia-induced neuronal damage and the efficacies of antagonists were reviewed by Hara et al. (1994). Recendy, using caspase-1 knockout or transgenic mice (Friedlander et al., 1997) and Bcl-2 transgenic mice (Martinou et al., 1994), it was shown that the neuronal cell death induced by cerebral ischemia includes apoptosis. 

Activation of calpain is usually associated with the progression of a necrotic type of cell death (Wang, 2000). However, neuronal necrosis and apoptosis occur in parallel after ischemic injury in vitro and in vivo (Charriaut-Marlangue et al., 1996). Retinal ischemia causes precocious necrosis of neurons in the ganglion cell layer (GCL) and INL, whereas apoptosis appears as the delayed component of neuronal death associated with transient retinal ischemia (Joo et al., 1999). 

Li R, Yang L, Lindhohn K, Konishi Y, Yue X, Hampel H, Zhang D, Shen Y (2004) Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death. J Neurosci 24 1760-1771. 

IL-1 and tumor necrosis factor (TNF) are proinflammatory cytokines. They are produced in response to adverse stimuli. Each cytokine exists as two well-characterized isoforms IL-lot and IL-1P, and TNF-ot and TNF-p, respectively. There is strong evidence for the involvement of IL-1P and TNF ot in the pathogenesis of experimental brain ischemia (Hallenbeck, 2002 Patel et al., 2003). In the retina, transient ischemia causes upregulation of TNF-ot (Fontaine et al., 2002). In the early phase of reperfusion, TNF-ot is primarily upregulated in ganglion cells, amacrine cells, and Muller cells. There is no consensus about the overall efiect of TNF-ot on retinal cell viability. There is an indication that activation of TNF receptor 2 is neuroprotective, whereas activation of TNF receptor 1 augments neuronal death. 

Portera-Cailliau, C, Price, D. L and Martin, L. J. (1997) Non-NMDA and NMDA receptor-mediated excitotoxic neuronal deaths in adult brain are morphologically distinct further evidence for an apoptosis-necrosis continuum. J. Comp. Neurol. 378(1), 88-104. 

Marchetti L, Klein M, Schlett K, Pflzenmaier K, Eisel UL (2004) Tumor necrosis factor (TNE)-mediated neuroprotection against glutamate-induced exdtotoxicity is enhanced by iV-methyl-D-aspartate receptor activation. Essential role of a TNE receptor 2-mediated phos-phatidyUnositol 3-kinase-dependent NE-kappa B pathway. J Biol Chem 279 32869-32881 Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP (1997) A role for 4-hydroxynonenal, an aldehydic produd of Upid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid p-peptide. J Neurochem 68 255-264 Mattson MP, Meffert MK (2006) Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ 13 852-860... 

As stated in Chapter 2, the activation of these enzymes causes neuronal death by necrosis and/or apoptosis, via ROS and RNS generation, proteolysis, and DNA damage (Fig. 3.3) (Farooqui et al., 2008). ROS modulate p38/MARK, JNK/MARK, ERK/MARK pathways and RNS activate PARP-1. Under these conditions, in the infarct core neuronal death occurs within minutes to less than an hour (Lo et al., 2003). This is followed by a second wave of neuronal demise in the ischemic penumbra and neuroanatomically connected sites. This delayed cell death (secondary degeneration) occurs via apoptosis and often exceeds the initial damage of... 

Cole KK, Perez-Polo JR. Poly(ADP-ribose) polymerase inhibition prevents both apoptotic-like delayed neuronal death and necrosis after H(2)0(2) injury. J Neurochem 2002 82 19-29. 

Hypoglycemia may be summarized as a novel insult that has a number of features unsuspected several decades ago. These include a positive, excitotoxic mechanism of neuronal death, not merely nenronal death by starvation. Asymmetry is sometimes seen, and is explained by the asynchronous onset of electrocerebral silence between the hemispheres. And selective necrosis of the dentate gyrus is not seen in cerebral ischemia, the dentate being the last structure within the hippocampus to be destroyed by ischemia. Based on these principles, it is sometimes possible to tell hypoglycemic from ischemic brain damage in human brains. 

Miura Y, Misawa N, Kawano Y, Okada H, Inagaki Y, Yamamoto N et al. Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection. Proceedings of the national academy of sciences of the United States of America 2003b 100(5) 2777-2782... 

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