Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats

Kao, Tsung-Kuei; Ou, Yen‐Chuan; Kuo, Jong-Song; Chen, Wen-Yin; Liao, Su‐Lan; Wu, Ching-Wen; Chen, Chun‐Jung; Ling, Nai-Nu; Zhang, Yonghong; Peng, Wen-Huang

doi:10.1016/j.neuint.2005.10.008

Cited by 138 publications

(100 citation statements)

References 43 publications

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“…The beneficial effects of TMP on the CNS against stresses have previously been demonstrated (Liao et al, 2004;Kao et al, 2006). TMP significantly attenuates neural cell damage in the CNS in response to either toxic or traumatic insults and shows strong anti-oxidant activity (Shih et al, 2002;Liao et al, 2004).…”

Section: Discussionmentioning

confidence: 89%

“…Conversely, downregulation of humanin sensitizes cells to Bax and increases Bax translocation to membranes and promotes the release of cytochrome c for progression of programmed cell death (Guo et al, 2003). TMP treatment significantly attenuated cytochrome c release and activation of caspases in ischemic brain or PC12 cells exposed to H 2 O 2 Kao et al, 2006). Thus, our findings support the idea that TMP preserves expression of humanin/rattin to contribute to its mitoprotective effects and to promote, in part, retinal cell survival against attacks, although further studies are warranted to explore the mechanism of TMP-mediated preservation of rattin expression.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies found that TMP protected mitochondrial function through regulating expressions of mitochondrial Bcl2 family proteins that directly modulate mitochondrial permeability in the central nervous system (CNS) Kao et al, 2006). Since the mitochondrial integrity is modulated by humanin/rattin, we sought to examine whether TMP also modulates expression of rattin in retinal cells to contribute to its neuroprotective effects.…”

Section: Tmp Inhibited Ros-induced Downregulation Of Rattin Associatementioning

confidence: 99%

“…TMP is also demonstrated as a calcium antagonist (Pang et al, 1996). Systemic administration of TMP protected neuronal cells against ischemic or traumatic brain or spinal cord injury and promoted functional recovery in rodents and rabbit (Fan et al, 2006;Kao et al, 2006). Improvements of learning and cognitive function by TMP were also reported in rodents following D-galactose-or arterial occlusion-induced brain lesions (Ni et al, 1995;Zhang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of tetramethylpyrazine on rat retinal cell cultures

Yang

Zhang

et al. 2008

Neurochemistry International

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The retinal degeneration characterized with death of retinal ganglion cells is a pathological hallmark and the final common pathway of various optic neuropathies. Thus, there is an urgent need for identifying potential therapeutic compounds for retinal protection. Tetramethylpyrazine has been suggested to be neuroprotective for central neurons by acting as an antioxidant and a calcium antagonist. In this study, we tested the effects of tetramethylpyrazine on the viability of both neuronal and non-neuronal cells in mixed rat retinal cell cultures during a long-term cultivation or following hydrogen peroxide treatments. Cellular and biochemical analyses demonstrated that 50 μM tetramethylpyrazine significantly preserved neuronal morphology and survival in retinal cell cultures following 4-week in vitro cultivation as well as lethal exposures to hydrogen peroxide (10μM or 50 μM for 24 hr). Hydrogen peroxide treatments induced remarkable increases in lipid peroxidation and mitochondrial ROS generation paralleled by the loss of mitochondrial membrane potential, microtubule-associated protein-2 (MAP-2) in neuronal soma and rattin peptide in cultured cells. Addition of tetramethylpyrazine in the cultures efficiently attenuated the signs of oxidative stress and retained abundance of MAP-2 and rattin in association with cell survival. In addition, siRNAmediated downregulation of MAP-2 or rattin significantly increased the vulnerability of retinal neurons or the number of degenerating cells in the cultures, respectively, whereas exogenous humanin peptide, an analog of rattin, promoted cell survival in cultures under hydrogen peroxide attacks. These results suggest that tetramethylpyrazine protect retinal cells through multiple pathways and might be a potential therapeutic candidate for retinal protection in certain optic neuropathies.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Tmp Inhibited Ros-induced Downregulation Of Rattin Associatementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Protective effects of tetramethylpyrazine on rat retinal cell cultures

Yang

Zhang

et al. 2008

Neurochemistry International

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“…Intraperitoneal administration of TMP was found to significantly protect the brain from ischemic insult, as shown by the reduction in infarction volume, neuronal loss, behavioral disturbance, and brain edema (Liao et al, 2004;Kao et al, 2006). TMP may provide neuroprotection against ischemia brain injury by inducing thioredoxin transcription (Zhu et al, 2009) or by reducing nNOS expression (Xiao et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

Yang

Huang

Jiang

2015

Braz. J. Pharm. Sci.

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Tetramethylpyrazine (TMP), a major active ingredient of Ligusticum wallichi Franchat extract (a Chinese herb), exhibits neuroprotective properties in ischemia. In this study, we assessed its protective effects on Schwann cells (SCs) by culturing them in the presence of oxygen glucose deprivation (OGD) conditions and measuring cell survival in cold ischemic rat nerves. In the OGD-induced ischemic injury model of SCs, we demonstrated that TMP treatment not only reduced OGD-induced cell viability losses, cell death, and apoptosis of SCs in a dose-dependent manner, and inhibited LDH release, but also suppressed OGD-induced downregulation of Bcl-2 and upregulation of Bax and caspase-3, as well as inhibited the consequent activation of caspase-3. In the cold ischemic nerve model, we found that prolonged cold ischemic exposure for four weeks was markedly associated with the absence of SCs, a decrease in cell viability, and apoptosis in preserved nerve segments incubated in University of Wisconsin solution (UWS) alone. However, TMP attenuated nerve segment damage by preserving SCs and antagonizing the decrease in nerve fiber viability and increase in TUNEL-positive cells in a dose-dependent manner. Collectively, our results indicate that TMP not only provides protective effects in an ischemia-like injury model of cultured rat SCs by regulating Bcl-2, Bax, and caspase-3, but also increases cell survival and suppresses apoptosis in the cold ischemic nerve model after prolonged ischemic exposure for four weeks. Therefore, TMP may be a novel and effective therapeutic strategy for preventing peripheral nervous system ischemic diseases and improving peripheral nerve storage. Uniterms:Tetramethylpyrazine. Schwann cell. Oxygen glucose/deprivation. Peripheral nerve. Ischemia/ experimental study. University of Wisconsin solution.Tetrametilpirazina (TMP), o principal componente do extrato de Ligusticum wallichi Franchat (erva chinesa), apresenta propriedades neuroprotetoras na isquemia. Nesse estudo, avaliamos seus efeitos protetores nas células de Schwann (SC), cultivando-as na presença de condições de depleção de oxigênio da glicose (OGD) e medindo a sobrevivência dos nervos de ratos isquêmicos pelo resfriamento. No modelo de lesão isquêmica em SC induzida por OGD, demonstramos que o tratamento com TMP não somente reduziu as perdas de viabilidade celular induzida por OGD, a morte celular, a apoptose de SC dose-dependente e inibiu a liberação de LDH, mas, também, suprimiu a infra-regulação do Vcl-2 e a supra-regulação de Bax e caspase-3, e inibiu a consequente ativação da caspase-3. No modelo de nervo isquêmico por resfriamento, observamos que a exposição prolongada ao resfriamento por quatro semanas estava, marcadamente, associada com a ausência de SC, com o decréscimo da viabilidade celular e a apoptose em segmentos de nervo incubados na solução da Universidade de Wisconsin apenas. Entretanto, a TMP atenuou o dano no segmento do nervo preservando SC e antagonizando a diminuição da viabilidade da fibra nervosa e o aumento das cé...

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Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia‐Reperfusion Injury

Yao

Syeda

et al. 2023

Advanced Science

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Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl‐F‐(D)L‐F‐(D)L‐F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)‐responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation‐related diseases.

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Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats

Cited by 138 publications

References 43 publications

Protective effects of tetramethylpyrazine on rat retinal cell cultures

Protective effects of tetramethylpyrazine on rat retinal cell cultures

Tetramethylpyrazine protects Schwann cells from ischemia-like injury and increases cell survival in cold ischemic rat nerves

Ligustrazine Nanoparticle Hitchhiking on Neutrophils for Enhanced Therapy of Cerebral Ischemia‐Reperfusion Injury

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