Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression

Xu, Zhen; Ford, Gregory D.; Croslan, DaJoie R.; Jiang, Ju; Gates, Alicia; Allen, Robert; Ford, Byron D.

doi:10.1016/j.nbd.2005.01.027

Cited by 107 publications

(93 citation statements)

References 34 publications

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“…Reperfusion following MCAO was associated with apoptotic cell death and inflammation. We and others have shown that neuroprotection by NRG-1 involves the inhibition of apoptotic and pro-inflammatory responses [16,30,36,37]. NRG-1 prevented mononuclear infiltration, astrocyte activation and cytokine production, which are known to be associated with delayed neuronal death following ischemia [36,37].…”

Section: Discussionmentioning

confidence: 82%

“…It is plausible that NRG-1 was not equally effective in the pMCAO model due to additional mechanisms that may be involved in pMCAO that are not available to NRG-1 treatment. Previous results from our laboratory using EASE software [12] showed that tMCAO/reperfusion was associated with apoptotic cell death and inflammation, which have been shown to be blocked by NRG-1 [16,36,37]. EASE identified distinct pathways upregulated in the pMCAO model that were related to excitotoxicity, including neurotransmission and ion channel function.…”

Section: Combination Treatment With Nrg-1 and Mk-801 Prevents Infarctmentioning

confidence: 88%

“…We and others have shown that neuroprotection by NRG-1 involves the inhibition of apoptotic and pro-inflammatory responses [16,30,36,37]. NRG-1 prevented mononuclear infiltration, astrocyte activation and cytokine production, which are known to be associated with delayed neuronal death following ischemia [36,37]. Since NRG-1 has been shown be ineffective against excitotoxic injury in neurons [21], we examined whether co-treatment with NRG-1 and an inhibitor of excitotoxicity could have synergistic neuroprotective effects in the pMCAO model.…”

Section: Discussionmentioning

confidence: 99%

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Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Ford

et al. 2007

Brain Research

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Neuregulin-1 (NRG-1) is a growth factor with potent neuroprotective capacity in ischemic stroke. We recently showed that NRG-1 reduced neuronal death following transient middle cerebral artery occlusion (tMCAO) by up to 90% with an extended therapeutic window. Here, we examined the neuroprotective potential of NRG-1 using a permanent MCAO ischemia (pMCAO) rat model. NRG-1 reduced infarction in pMCAO by 50% when administered prior to ischemia. We previously demonstrated using gene expression profiling that pMCAO was associated with an exaggerated excitotoxicity response compared to tMCAO. Therefore, we examined whether co-treatment with an inhibitor of excitotoxicity would augment the effect of NRG-1 following pMCAO. Both NRG-1 and the N-methyl-D-aspartate (NMDA) antagonist MK-801 similarly reduced infarct size following pMCAO. However, combination treatment with both NRG-1 and MK-801 resulted in greater neuroprotection that either compound alone, including a 75% reduction in cortical infarction compared to control. Consistent with these findings, NRG-1 reduced neuronal death using an in vitro ischemia model and this effect was augmented by MK-801. These results demonstrate the efficacy of NRG-1 in pMCAO rat focal ischemia model. Our findings further indicate the potential clinically relevance of NRG-1 alone or as a combination strategy for treating ischemic stroke.

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Section: Discussionmentioning

confidence: 82%

Section: Combination Treatment With Nrg-1 and Mk-801 Prevents Infarctmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

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Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Ford

et al. 2007

Brain Research

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“…Антиапоптотический эффект ПреК опосредован увеличением интенсивности синтеза ряда факторов роста и трофогенов, в частности фактора роста нервов, мозгового нейротрофического фактора (BDNF), инсулиноподобного фактора роста-1 (IGF1), основ-ного фактора роста фибробластов (bFGF) и белков-нейрегулинов [1,3,4].…”

Section: антиапоптотическое действие прекондиционированияunclassified

Molecular Mechanisms of Development of Cerebral Tolerance to Ischemia (Review. Part 2)

Шляхто¹,

Баранцевич²,

Shcherbak³

et al. 2012

Annals RAMS

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Антиапоптотическое действие прекондиционированияИшемия и в особенности реперфузия запускают процесс программируемой гибели нейронов -апоптоз, механизмы которого на сегодняшний день достаточно хорошо изучены. При прекондиционировании головного мозга (ПреК ГМ) запускаются многочисленные процессы, препятствующие апоптозу, которые могут быть связаны с активацией рецепторов, внутриклеточных киназных каскадов, транскрипционных факторов, определенных митохондриальных белков и ядерных эффекторов. Более подробная характеристика молекулярных механизмов, участвующих как в запуске апоптоза, так и в его предот-вращении в процессе наступления ишемической толе-рантности, представлена в табл. 1. Известно, в частности, что индуцируемый ПреК транскрипционный фактор -цАМФ-зависимый связывающий белок (CREB) -способствует увеличению интенсивности синтеза анти-апоптотических белков BCL2 и BCLX L . Кроме того, под действием ПреК происходит стабилизация митохондри-ального мембранного потенциала, снижается высвобож-дение митохондриального цитохрома С, а также умень-шается интенсивность синтеза каспазы 3 и снижается активность ядерного белка p53 [1]. На модели четырех-сосудистой ишемии ГМ у крыс было показано, что меха-низмы предотвращения апоптоза нейронов СА1-зоны гиппокампа под действием ишемического ПреК вклю-чают активацию фосфатидилинозитол-3ОН-киназы (PI3K) и протеинкиназы В с последующей блокировкой сигнальных путей апоптоза [2]. В частности, ишемиче-ское ПреК предотвращало транслокацию в митохон-дрии проапоптотического фактора BAD, его связывание с BCL-X L и расщепление последнего с образованием проа-поптотического фрагмента ∆N-Bcl-X L . Помимо этого,

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“…No satisfactory therapies that limit neuronal damage and neurological dysfunction after stroke in humans are currently available. While the exact molecular mechanisms that govern stroke-induced neuronal death are not yet known, massive inflammation is implicated in secondary ischemic brain damage (Zhang and Stanimirovic, 2002;Xu et al, 2005;Khan et al, 2005). Investigations using genetically altered cyclooxygenase (COX) knockout mice provided novel information about COX-2.…”

Section: Introductionmentioning

confidence: 99%

Kinetic Changes of COX-2 Expression during Reperfusion Period after Ischemic Preconditioning Play a Role in Protection Against Ischemic Damage in Rat Brain

Kang

Park

Lee

et al. 2008

Korean J Physiol Pharmacol

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A brief ischemic insult induces significant protection against subsequent massive ischemic events. The molecular mechanisms known as preconditioning (PC)-induced ischemic tolerance are not completely understood. W e investigated whether kinetic changes of cyclooxygenase (COX)-2 during reperfusion time-periods after PC were related to ischemic tolerance. Rats were given PC by occlusion of middle cerebral artery (MCAO) for 10 min and sacrificed after the indicated time-periods of reperfusion (1, 2, 4, 8, 12, 18 or 24 h). In PC-treated rats, focal ischemia was induced by occlusion of MCA for 24 h and brain infarct volume was then studied to determine whether different reperfusion time influenced the damage. W e report that the most significant protection against focal ischemia was obtained in rats with 8 h reperfusion after PC. Administration of indomethacin (10 mg/kg, oral) or rofecoxib (5 mg/kg, oral) 48 h prior to PC counteracted the effect of PC. Immunohistochemical analysis showed that COX-2 and HO-1 protein were induced in PC-treated rat brain, which was significantly inhibited by rofecoxib. Taken together, we concluded that the kinetic changes of COX-2 expression during the reperfusion period after PC might be partly responsible for ischemic tolerance.

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Neuroprotection by neuregulin-1 following focal stroke is associated with the attenuation of ischemia-induced pro-inflammatory and stress gene expression

Cited by 107 publications

References 34 publications

Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Molecular Mechanisms of Development of Cerebral Tolerance to Ischemia (Review. Part 2)

Kinetic Changes of COX-2 Expression during Reperfusion Period after Ischemic Preconditioning Play a Role in Protection Against Ischemic Damage in Rat Brain

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