Necrosis, of neurons

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). 

Neurons arc responsible for the perception of sensory. stimuli and the coordination of cellular. ti.ssuc. and organis-mal responses to stimuli from the environment. Among the possible effects of neurotoxicants on neurons arc several general responses apopto.sis or necrosis of neuronal stem cells in both the developing and the mature brain, impaired... 

Perhaps the most likely mechanism of low thiamine-induced brain injury has revolved around impairment of the Krebs cycle and deficit in available ATP (Desjardins and Butterworth, 2005). This could readily lead to apoptosis and necrosis of neurons, as has been described in such patients (Vorhees et al, 1977). In this context, the data on pyruvate dehydrogenase are somewhat difficult to interpret. Postmortem brain from patients with Wernicke s encephalopathy did show a major decrease in pyruvate dehydrogenase, albeit in only a few specimens (Butterworth et al, 1993). However, this was not corroborated in experimental models of this syndrome (Desjardins and Butterworth, 2005 Butterworth et al., 1993). By contrast a major decrease in brain a-ketoglutarate dehydrogenase was seen in every type of thiamine deficiency (Desjardins and Butterworth, 2005 Butterworth et al., 1993). Moreover, an impairment in this enzyme could readily explain an increase in brain lactate, due to anaerobic metabolism, and this has been observed uniformly, even... 

Forms carboxyhemoglobin, leading to severe anoxia, which causes anoxic degeneration and necrosis of neurons... 

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

Representative photomicrographs of neuronal immunostaining with antibodies recognizing neuron specific enolase (a) and tumor necrosis factor alpha (b) in vitro (c) and ex vivo (d) immunostaining of astrocytes with antibodies recognizing glial fibrillary acidic protein microglial cells with ED-1 (e) and OX-42 (f) antibodies... 

Neuronal cell death is required for the development of the nervous system. However, recent studies suggest that neurons die from programmed cell death (apoptosis) in brains deprived of oxygen by stroke [14] and trauma [15], and in the brains of Alzheimer s patients [16], Therefore, prevention of neuronal apoptosis has been considered to be a desirable therapeutic strategy for treating such neurodegenerative diseases, although the value of this approach is not yet evident. We have recently reported that crocin suppresses tumor necrosis factor (TNF)-a-... 

Following short-term inhalation exposure to 160 ppm [620 mg/m ] methyl bromide (6 h per day on five days per week for up to six weeks), B6C3F, mice were found to be more sensitive than Fischer 344/N rats 50% of male mice died after eight exposures and 50% of female mice after six exposures, while similar mortality was observed in male rats only after 14 exposures. Neuronal necrosis and testicular degeneration were observed in both species nephrosis was observed in nearly all mice, while necrosis of the olfactory epithelium was more marked in rats. Myocardial degeneration occurred in rats and to a lesser degree in male mice. In the adrenal cortex, there was cytoplasmic vacuolation in rats and inner zone atrophy in female mice (Eustis et al., 1988). 

Especially in models of transient cerebral ischemia, apoptotic cell death has been observed after 3-7 days post insult in selected brain regions in which basal energy metabolism has been preserved (Chen et al. 1997 Du et al. 1996). In the meantime, molecular switches have been identified that gate different populations of neurons with regard to the type of cell death they eventually undergo (Nicotera 2003). However, there is little doubt that in animal stroke the vast majority of cells would die from necrosis or, alternatively, secondary energy failure even in the presence of a pro-apop-totic genetic balance. The concept of thresholds of cerebral blood flow (CBF) for various functions of brain parenchyma (see below) explains why the infarct core suffers from pan-necrosis whereas the peri-infarct border in which function is suppressed, but structure initially preserved (the so-called ischemic penumbra), may show apoptotic cell death or a combination of both. 

Laminar necrosis is a rare manifestation of neuronal injury with a very poor prognosis. Laminar necrosis often follows hypotension of relatively slow onset but of long duration. The process thus results from oxygen or glucose depletion caused by anoxia, hypoglycemia, status epilepticus, or ischemic stroke. Most of our patients had some form of circulatory failure. 

---