Hypoxia-ischemia apoptosis

Hypoxia-ischemia may initiate apoptosis in parallel with excitotoxicity 565 Triggers of ischemic apoptosis may include decreased supply or sensitivity to neurotrophins, oxidative stress, exposure to inflammatory cytokines or damage to mitochondria 566... 

Hill I. E., MacManus J. R, Rasquinha I., and Tuor U. I. (1995). DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxia-ischemia in the neonatal rat. Brain Res. 676 398 103. 

Blomgren, K., Zhu, C., Wang, X., et al., 2001, Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia a mechanism of pathological apoptosis , J. Biol. Chem., 276, 10191-10198... 

S100B Overexpression Female specific hyperactivity, lack of habituation to novelty, reduced T-maze spontaneous alternation rate, abnormal exploratory behavior Enhanced astrocytosis and neurite proliferation Impaired learning and memory, increased dendrite density, enhanced age-related loss of dendrites Inhibitory effect on cardiac hypertrophy Increased susceptibility to hypoxia-ischemia Increased apoptosis after myocardial infarction Enhanced neuroinflammation and neuronal dysfunction induced by amyloid-(3... 

Knock-out Increased synaptic plasticity, spatial memory and fear memory Chronic gliosis Decreased susceptibility to hypoxia-ischemia Enhanced epileptogenesis Enhanced Ca2+ transients Enhanced hypertrophy, decreased apoptosis and improved hemodynamics after myocardial infarction... 

Stress stimuli come in a variety of forms, such as deprivation of trophic factors, ionizing radiation, free radicals (e.g., peroxynitrite), hypoxia, ischemia, heat shock, lipid second messengers (such as ceramide) (Singh et al., 1998), TNF-a, or Fas-ligand. In the brain, neurons are especially susceptible to stress stimuli these stimuli lead to activation of intracellular pathways that either promote apoptosis or defense-adaptation mechanisms. At least three such pathways have been well studied. These pathways lead to the activation of c-Jun N-terminal kinases (JNKs), p38 kinases. 

Zhu C, Qiu L, Wang X et al. Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain. J Neurochem 2003 86(2) 306-17. 

In studies in vitro, caspases are involved in hypoxic [62,64] injury to RTE cells. Antimycin A-induced chemical hypoxia [64] or growth under hypoxic conditions results in increased caspase activity and pancaspase inhibition prevents hypoxia-induced DNA fragmentation and cell death in RTE cells. Partial ATP depletion of MDCK cells by antimycin A was also shown to result in apoptosis with marked increase in activation of caspase-8 and inhibition of caspases provided marked protection against antimycin A-induced cell death [65]. Exposure of freshly isolated RTE to hypoxia resulted in caspase activation and cell membrane damage [66]. In a related study, activation of caspase-3 during hypoxia or ATP depletion was shown to be accompanied by bax translocation and cytochrome c release [67]. As in ischemia, cisplatin activates the caspase cascade as well. Cisplatin induces selective and differential activation of caspases including executioner caspase-3... 

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