Neuroprotective effects of prostaglandin A1 in animal models of focal ischemia

Zhang, Huiling; Huang, Zhi Hong; Zhu, Yi; Liang, Zhong-Qing; Han, Rong; Wang, Xiaoxia; Chase, Thomas N.; Qin, Zheng‐Hong

doi:10.1016/j.brainres.2005.01.046

Cited by 22 publications

(22 citation statements)

References 24 publications

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“…A pivotal role of NF‐κB in the regulation of cell survival and death has been suggested. Although reported findings are controversial, strong evidence supports the notion that activation of NF‐κB in neurons contributes to ischemia‐induced neuronal injury (Clemens et al, 1998; Schneider et al, 1999; Ueno et al, 2001; Huang et al, 2001; Zhang et al, 2005). Several proapoptotic genes induced by ischemia contain NF‐κB binding sites, including c‐Myc, which contributes to ischemia‐induced neuronal apoptosis (Qin et al, 1999; Huang et al, 2001).…”

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confidence: 87%

“…Our previous in vivo and in vitro studies have demonstrated that PGA 1 can inhibit apoptosis in both neurons and neuron‐like cells induced by excitotoxin and mitochondria toxins (Qin et al, 2001; Wang et al, 2002). Recently, we have reported that PGA 1 can reduce infarct size in rodent models of focal cerebral ischemia, suggesting that PGA 1 has a neuroprotective effect against cerebral ischemic insults (Zhang et al, 2005). These underlying mechanisms of the neuroprotective effect of PGA 1 are not well understood, although induction of heat shock proteins appears to be involved (Xu et al, 2006).…”

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confidence: 99%

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Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Zhang

Gu²,

Savitz

et al. 2007

J of Neuroscience Research

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We have previously reported that prostaglandin A(1) (PGA(1)) reduces infarct size in rodent models of focal ischemia. This study seeks to elucidate the possible molecular mechanisms underlying PGA(1)'s neuroprotective effects against ischemic injury. Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) by intraluminal suture blockade. PGA(1) was injected intracerebroventricularly (icv) immediately after ischemic onset. Western blot analysis was employed to determine alterations in IkappaBalpha, pIKKalpha, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Immunohistochemistry was used to confirm the nuclear translocation of nuclear factor-kappaB (NF-kappaB) p65 and the expression of PPAR-gamma. RT-PCR was used to detect levels of c-Myc mRNA. The contribution of PPAR-gamma to PGA(1)'s neuroprotection was evaluated by pretreatment with the PPAR-gamma irreversible antagonist GW9662. A brief increase in pIKKalpha levels and rapid reduction in IkappaBalpha were observed after ischemia. PGA(1) blocked ischemia-induced increases in pIKKalpha levels and reversed the decline in IkappaBalpha levels. Ischemia-induced nuclear translocation of NF-kappaB p65 was attenuated by PGA(1). PGA(1) also repressed the ischemia-induced increase in expression of NF-kappaB target gene c-Myc mRNA. Immunohistochemistry demonstrated an increase in PPAR-gamma immunoreactivity in the nucleus of striatal cells at 3 hr after pMCAO. Western blot analysis revealed that the expression of PPAR-gamma protein significantly increased at 12 hr and peaked at 24 hr. PGA(1) enhanced the ischemia-triggered induction of PPAR-gamma protein. Pretreatment with the irreversible PPAR-gamma antagonist GW9662 attenuated PGA(1)'s neuroprotection against ischemia. These findings suggest that PGA(1)-mediated neuroprotective effect against ischemia appears to be associated with blocking NF-kappaB activation and likely with up-regulating PPAR-gamma expression.

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confidence: 87%

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confidence: 99%

Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Zhang

Gu²,

Savitz

et al. 2007

J of Neuroscience Research

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“…Drug development studies require the use of both types of focal ischemia models, before translating the compound to human trials [32]. Because of the differences in pathopysiological mechanisms induced with each type of ischemia, a drug found effective in a permanent model may be less effective [33,34] or ineffective in the transient model or vice versa; effectiveness proved in a transient ischemic model may be reduce [35] or vanish [36] when the model is permanent. Additionally, the therapeutic window of the drug may differ between permanent and transient ischemia settings [37].…”

Section: Model Selectionmentioning

confidence: 99%

Rodent Models of Ischemic Stroke: A Useful Tool for Stroke Drug Development

Durukan

Strbian²,

Tatlısumak

2008

CPD

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Stroke is the third common cause of death and the most common cause of adult disability. Approximately 80% of all strokes are ischemic (brain infarction). The only approved acute therapy is intravenous thrombolysis with tissue plasminogen activator within 3 h of symptom onset but only a small percentage of all ischemic stroke patients can receive this therapy. Therefore, novel therapeutic approaches directed at the pathophysiological mechanisms involved in ischemic brain injury are urgently needed. To this end several experimental stroke models were developed. These models are indispensable for understanding the pathophysiology of brain ischemia and to develop novel drugs and investigative methodology. This review considers the most commonly used ischemic stroke models (including preconditioning models) in rodents emphasizing their advantages and disadvantages. Since none of the models can perfectly simulate human stroke, researchers must interpret experimental findings carefully.

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“…The deletion of the neuronal IKK2 subunit or inhibition of IKK activity reduced the infarct size and neuronal cell loss. The role of NF-κB in neuronal death was further suggested, as several neuroprotective agents, such as antioxidant LY231617, PDTC, and PGA1, have been shown to inhibit NF-κB activation, reduce infarct volume, and improve behavior deficits [110,173,174] . The contribution of NF-κB activation to ischemic neuronal damage has also been assessed with either the expression of mutant IκB-α in neurons and glial, or NF-κB p50 knockout mice and transgenic mice.…”

Section: Ischemic Brain Injurymentioning

confidence: 99%

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

Qin

Tao

Chen

2007

Acta Pharmacologica Sinica

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NF-κB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-κB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-κB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-κB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-κB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-κB, leading to speculation that blocking the pathological activation of NF-κB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-κB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-κB that are involved in cell death and survival to elucidate why NF-κB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-κB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-κB is a potential target for neuroprotective therapy.

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Neuroprotective effects of prostaglandin A1 in animal models of focal ischemia

Cited by 22 publications

References 24 publications

Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Rodent Models of Ischemic Stroke: A Useful Tool for Stroke Drug Development

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

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Neuroprotective effects of prostaglandin A1 in animal models of focal ischemia

Cited by 22 publications

References 24 publications

Neuroprotective effects of prostaglandin A1 in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Neuroprotective effects of prostaglandin A1 in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Rodent Models of Ischemic Stroke: A Useful Tool for Stroke Drug Development

Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy

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Product

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Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation

Neuroprotective effects of prostaglandin A₁ in rat models of permanent focal cerebral ischemia are associated with nuclear factor‐κB inhibition and peroxisome proliferator‐activated receptor‐γ up‐regulation