Neuroprotection and enhanced neurogenesis by tetramethylpyrazine in adult rat brain after focal ischemia

Xiao, Xinli; Liu, Yong; Qi, Cunfang; Qiu, Feifei; Chen, Xinlin; Zhang, Jianshui; Yang, Pengbo

doi:10.1179/174313209x414533

Cited by 76 publications

(57 citation statements)

References 34 publications

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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). In addition, some studies have reported that TMP has protective effects against cardiovascular diseases and ischemia-reperfusion damage in the kidney (Dai, Bache, 1985;Zhou et al, 2004;Feng et al, 2011).…”

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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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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“…The neural nitric oxide synthase (nNOS) expression in the cortex and DG was reduced by TMP. These results indicate that TMP could protect brain from ischemic damage and promote cell proliferation and differentiation, which might be related to the reduction of nNOS expression (6). Using the ischemic model induced by oxygen glucose deprivation in vitro, Si et al (7) observed that Panax notoginseng saponins, with blood-activating and stasis-dissolving properties, could promote proliferation and differentiation of hippocampal NSCs by enhancing the expression of Nestin/BrdU and mRNA expressions of Tuj-1, vimentin, and nestin in hippocampal NSCs, which suggested its potential benefits on neural regeneration in cerebral ischemic injury.…”

Section: Action Of Anti-ischemic Brain Injurymentioning

confidence: 95%

Neural Regeneration: Role of Traditional Chinese Medicine in Neurological Diseases Treatment

Ren

Zuo

2012

J Pharmacol Sci

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Abstract. The effects of a single compound and a mixture of traditional Chinese medicine (TCM) on promoting proliferation, differentiation, and migration of neural stem cells and regulating their microenvironment have been observed by Chinese scholars in recent years. These results showed good prospects in improving neural regeneration and repair of neurological disorders such as ischemic brain injury, Alzheimer's disease, Parkinson's disease, and depression. According to the TCM theory, the relationship between life of an individual and the disease was regarded as an entirety, and the theory emphasized the treatment based on syndrome differentiation since ancient times. In this paper, we attempted to introduce these medicines, which belong to natural products and have already been proved to possess clear therapeutic action on human bodies in the clinical setting. We summarized their effects promoting brain neurogenesis and repairing brain injuries in animal models and some mechanisms at the cellular and molecular levels.

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“…손상 보호효능 [5][6][7][8] 과 in vivo의 뇌허혈 손상에 대해 매우 많은 연구가 이루어졌다 [9][10][11][12][13][14][15][16][17] . 또한 뇌출혈 18) 과 척수의 허혈과 압박 손상에 대해서도 유의한 효능이 있다고 하였다 [19][20][21][22] .…”

Section: Tetramethylpyrazine (Tmp)은 川芎 (Ligusticum Wallichii Franchatunclassified

Effect of Tetramethylpyrazine on Pro-Inflammatory Cytokine Expressions in Mouse Brain Tissue following Intracerebroventricular Lipopolysaccharide Treatment

Choi¹,

Won²,

Yoo³

et al. 2013

The Korea Journal of Herbology

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Objectives : Tetramethylpyrazine (TMP) is an active ingredient in Ligusticum wallichii and has a wide range of neuroprotection effects. This study investigated anti-neuroinflammatory effect of TMP on brain regions in intracerebroventricular (i.c.v.) lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : TMP was administered intraperitoneally at doses of 10, 20, and 30 mg/kg at 1 h prior to LPS (3 mg/kg) i.c.v. injection. mRNA level of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, was measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Cyclooxygenase-2 (COX-2) positive cells in the hypothalamus was also observed using immunohistochemistry at 24 h after the LPS injection. Results : At a dose of 30 mg/kg TMP significantly attenuated up-regulation of TNF-α and IL-1β mRNA in the cerebral cortex and IL-1β mRNA in the hippocampus. In the hypothalamus, doses of 20 mg/kg and 30 mg/kg TMP significantly attenuated up-regulation of TNF-α, IL-1β, and IL-6 mRNA induced by the LPS injection. In addition, TMP (30 mg/kg) significantly reduced the number of COX-2 positive cells in the hypothalamus. Conclusion : These results indicate that TMP has an anti-inflammatory effect on neuroinflammation, especially in the hypothalamus, induced by LPS i.c.v. injection and suggest that TMP-containing Ligusticum wallichii may play a modulatory role on the systemic responses following hypothalamic inflammation.

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Neuroprotection and enhanced neurogenesis by tetramethylpyrazine in adult rat brain after focal ischemia

Abstract: These results indicate that TMP could protect ischemic brain damage, and promote cell proliferation and differentiation stimulated by ischemia, which might be related to the reduction of nNOS expression after treatment with TMP in rat cerebral ischemia model.

Cited by 76 publications

References 34 publications

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

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

Neural Regeneration: Role of Traditional Chinese Medicine in Neurological Diseases Treatment

Effect of Tetramethylpyrazine on Pro-Inflammatory Cytokine Expressions in Mouse Brain Tissue following Intracerebroventricular Lipopolysaccharide Treatment

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