Seizures neuronal death

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... 

Seizure maintenance is largely caused by glutamate acting on postsynap-tic N-methyl-D-aspartate and a-amino-3-hydroxy-5-methyl-isoxazole-4-propionate/akinate receptors. Sustained depolarization can result in neuronal death. 

Haberman, R. P., Samulski, R. J. and McCown, T. J. (2003). Attenuation of seizures and neuronal death by adeno-associated virus vector galanin expression and secretion. Nat. Med. 9(8), 1076-1080. 

Smith PD, McLean KJ, Murphy MA, Tumley AM, Cook MJ (2005) Seizures, not hippocampal neuronal death, provoke neurogenesis in a mouse rapid electrical amygdala kindling model of seizures. Neuroscience 136 405 15. 

Segal A failure to treat the seizures using Na" " channel anticonvulsants would suggest that the seizures were being expressed in a secondary fashion, for example resulting from kindling or neuronal death. 

The action of lobeline (237) as a nicotinic receptor agonist has continued to generate considerable interest. (-)-Lobeline demonstrated a potent hyperalgesic effect, similar to that of nicotine, when tested in the low intensity thermally evoked tail avoidance response assay [514]. It improved cognition and retention in rats comparably to nicotine [515]. Both 237 and nicotine exhibited anxiolytic effects in mice [516] and partially inhibited iV-methyl-D-aspartate-induced responses in rat cortical neurons in vitro [517]. It was a potent inhibitor of nicotine-induced prostration in rats (ED50 = 10 nM) and antagonized additional actions of nicotine including systolic blood pressure increases, seizure, and death [518]. 

Seizure-induced neuronal death involves both apoptotic and necrotic cell death both processes are intricately involved with mitochondrial function (Sloviter et al., 1996). Oxidative stress not only causes cell death but alters cellular biophysical characteristics, such as the band-pass frequency responses of neurons (Frantseva et al., 1998), possibly indicating a rapid reorganization of cellular networks into different functional assemblies (Morimoto et al., 2004). 

Amnesic shellfish poisoning The main toxin associated with ASP is the tricarboxylic amino acid domoic acid (Figure 2), responsible for a human intoxication characterized by a widespread neurological dysfunction, chronic loss of memory, and motor neuropathy. The potent neurotoxic actions of domoic acid are due to the activation of a subtype (non-NMDA) of glutamate neurotransmitter receptors, and the subsequent depolarization leading to seizures and neuronal death. 

However, the actual role of ERKl/2 seems to be dependent on various parameters since inhibition of ERKl/2 activation during focal ischemia [41], oxidative stress [42], and a model for hippocampal seizures [43] attenuated neuronal death and cellular injury, indicating a proapoptotic role for ERKl/2. In addition, the inhibition of ERKl/2 activation has been demonstrated to protect a mouse neuronal cell line and rat primary cortical neurons from oxidative stress-induced neurotoxicity [44]. 

Status epilepticus occurs because the brain fails to stop an isolated seizure. The exact reason for this failure is unknown and probably involves many mechanisms. A seizure is likely to occur due to a mismatch of excitatory and inhibitory neurotransmitters in the brain. The primary excitatory neurotransmitter in the brain is glutamate. Glutamate stimulates postsynaptic N-methyl-D-aspartate (NMDA) receptors in the brain, causing an influx of calcium into the cells and depolarization of the neuron. Sustained depolarization may maintain SE and eventually cause neuronal injury and death.7 The primary... 

The neuronal ceroid lipofuscinoses (CLN), also referred to as Batten s disease, are a group of disorders characterized by the accumulation of autofluorescent lipopigments. Clinical hallmarks include blindness, seizures, cognitive and motor decline and early death. Age of onset varies from infancy to adulthood. Eight genetic forms have been identified [4]. Two involve lysosomal acid hydrolases. CLN1 codes for palmitoyl protein thioesterase 1. Clinically it presents most often in infancy and leads to loss of active movement and visual contact by 3 years of age. It is most common in Finland, where its incidence is 1 20,000. CLN2 codes for a lysosomal pepstatin-insensitive acid protease. 

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