To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: a review on the stress-activated signaling pathways and apoptotic pathways

Liou, Anthony Kian-Fong; Clark, Robert S. B.; Henshall, David C.; Yin, Xiao‐Ming; Chen, Jun

doi:10.1016/s0301-0082(03)00005-4

Cited by 268 publications

(188 citation statements)

References 481 publications

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“…Transient forebrain or global ischemia arises as a consequence of cardiac arrest, cardiac surgery, profuse bleeding, near-drowning, and carbon monoxide poisoning and affects B200 000 Americans each year (Liou et al, 2003;Moskowitz et al, 2010;Ofengeim et al, 2011). Neurological sequelae include deficits in learning and memory.…”

Section: Strokementioning

confidence: 99%

“…Although all forebrain areas experience oxygen and glucose deprivation, a brief ischemic insult causes cell death primarily of CA1 pyramidal neurons, critical to memory formation and retrieval. Neuronal death, exhibiting characteristics of apoptosis and necrosis, is not detected until 2-3 days after ischemia (Liou et al, 2003;Moskowitz et al, 2010;Ofengeim et al, 2011). By 1 week after ischemia, the CA1 pyramidal cell layer can be virtually ablated.…”

Section: Strokementioning

confidence: 99%

“…After reperfusion, cells appear morphologically normal, exhibit normal intracellular Ca 2 + and regain the ability to generate action potentials for 24-72 h after the insult. A myriad of death cascades are activated, including caspase-dependent and independent apoptosis, mitochondrial release of cytochrome c, Smac/DIABLO and AIF, excitotoxicity, lipid peroxidation, and swelling (Liou et al, 2003;Lo et al, 2003;Zukin et al, 2004). Ultimately, there is a late rise in intracellular Ca 2 + and Zn 2 + , and death of CA1 neurons ensues, exhibiting hallmarks of apoptosis and necrosis.…”

Section: Strokementioning

confidence: 99%

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Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

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Section: Strokementioning

confidence: 99%

Section: Strokementioning

confidence: 99%

Section: Strokementioning

confidence: 99%

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Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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“…A halo of partially perfused tissue commonly surrounds the dense ischemic core after stroke where incomplete metabolic collapse means an energy-and gene-dependent process contributes to cell death. Here, apoptosis-associated pathways may contribute significantly to expansion of the infarct zone and this watershed zone is partially salvageable by various antiapoptotic interventions (Liou et al, 2003;Mehta et al, 2007). Traumatic brain injury results from mechanical or acceleration-deceleration injury to the brain and is usually divided into primary and secondary mechanisms.…”

Section: Neuronal Death After Cerebral Ischemia and Traumatic Brain Imentioning

confidence: 99%

“…The pathophysiology specific to TBI includes a hemorrhagic component and differences in the degree of metabolic changes, extent of focal versus diffuse injury, nonneuronal cell contributions, and white matter damage (Bramlett and Dietrich, 2004;Loane and Faden, 2010;Royo et al, 2003). Secondary damage is delayed and features prominent activation of cell death pathways due to deinnervation (Liou et al, 2003;Loane and Faden, 2010;Raghupathi et al, 2000). Microscopic and biochemical evidence supports apoptosis in cells undergoing secondary cell death and inhibitors of caspases can prevent TBI-induced neuronal death (Raghupathi et al, 2000;Royo et al, 2003).…”

Section: Neuronal Death After Cerebral Ischemia and Traumatic Brain Imentioning

confidence: 99%

In vivoContributions of BH3-Only Proteins to Neuronal Death Following Seizures, Ischemia, and Traumatic Brain Injury

Engel

Plesnila

Prehn

et al. 2011

J Cereb Blood Flow Metab

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The Bcl-2 homology (BH) domain 3-only proteins are a proapoptotic subgroup of the Bcl-2 gene family, which regulate cell death via effects on mitochondria. The BH3-only proteins react to various cell stressors and promote cell death by binding and inactivating antiapoptotic Bcl-2 family members and direct activation of proapoptotic multi-BH domain proteins such as Bax. Here, we review the in vivo evidence for their involvement in the pathophysiology of status epilepticus and contrast it to ischemia and traumatic brain injury. Seizures in rodents activate three potent proapoptotic BH3-only proteins: Bid, Bim, and Puma. Analysis of damage after seizures in mice singly deficient for each BH3-only protein supports a causal role for Puma and to a lesser extent Bim but, surprisingly, not Bid. In ischemia and trauma, where core aspects of the pathophysiology of cell death overlap, multiple BH3-only proteins are also activated and Bid has been shown to be required for neuronal death. The findings suggest that while each neurologic insult activates multiple BH3-only proteins, there may be specificity in their functional contribution. Future challenges include evaluating the remaining BH3-only proteins, explaining different causal contributions, and, if possible, exploring neurologic outcomes in mouse models deficient for multiple BH3-only proteins.

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Role of the Fas-Signaling Pathway in Photoreceptor Neuroprotection

et al. 2007

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To determine whether inhibiting the Fas proapoptosis pathway will result in increased photoreceptor survival after separation of the retina from the retinal pigment epithelium (RPE). Methods: Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Fas-pathway signaling was inhibited by the concomitant injection of a Fas receptor-neutralizing antibody, small inhibitory RNA against the Fas-receptor transcript (siFAS), or the use of the Fas-receptor defective mouse strain LPR. Indices of photoreceptor death included terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, cell counts, and retinal thickness measurements. Retinas were immunostained with antibodies against rhodopsin and cone opsin to evaluate rod and cone photopigment production, respectively. Results: Inhibition of Fas signaling using Fas receptorneutralizing antibody, siFas, or LPR mice resulted in a significant reduction in the number of TUNEL-positive photoreceptor cells as well as in a significant preservation of outer nuclear layer cell counts and thickness as compared with retina/RPE separation in eyes with intact Fas signaling. Fas-pathway inhibition resulted in preservation of both rhodopsin-and cone opsin-positive cells. Conclusions: Inhibition of the Fas proapoptosis pathway results in significant photoreceptor preservation after retinal separation from the RPE. Clinical Relevance: Fas-pathway inhibition might serve as a novel mechanism for preserving photoreceptor cells during retinal disease.

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To die or not to die for neurons in ischemia, traumatic brain injury and epilepsy: a review on the stress-activated signaling pathways and apoptotic pathways

Cited by 268 publications

References 481 publications

Epigenetic Mechanisms in Stroke and Epilepsy

Epigenetic Mechanisms in Stroke and Epilepsy

In vivoContributions of BH3-Only Proteins to Neuronal Death Following Seizures, Ischemia, and Traumatic Brain Injury

Role of the Fas-Signaling Pathway in Photoreceptor Neuroprotection

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