Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: Therapeutic time window and its mechanism

Jia, Jie; Zhang, Xi; Hu, Ya-Han; Wu, Yi; Wang, Qingzhi; Li, Nana; Wu, Caiqin; Yu, Huixian; Guo, Qiaoyue

doi:10.1016/j.thromres.2008.11.004

Cited by 37 publications

(20 citation statements)

References 19 publications

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“…Additionally, compared with the vehicle group, the latency times were significantly decreased in the TMP group. (B) When the first two injection administrations were deprived in the TMP and vehicle groups [TMP (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and vehicle (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)], there were no significant differences in latency time between the TMP (2-14), vehicle and vehicle (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) groups. Data are presented as the mean ± standard error of the mean.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, compared with the vehicle group, the TMP group displayed significantly improved performance. When the first two injection administrations were not applied in the TMP and vehicle groups, there were no significant differences in performance between the TMP (2-14), vehicle and vehicle (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) accepted in the research of behavioral neuroscience for laboratory rodents (34). In order to remove the interference by visual and/or motor changes after TBI, we first assessed the visible platform test.…”

Section: Discussionmentioning

confidence: 99%

“…For the assessment of cognitive recovery (i.e. Morris water maze (MWM) trial), deprivation of injection administration on the same day of the TBI procedure was specified as TMP (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) group (n=6) and vehicle (2-14) group (n=6). All procedures were approved by the Soochow University Animal Ethics Committee and conformed to the Guide for the Care and Use of Laboratory Animals.…”

Section: Experimental Animals and Drug Administrationmentioning

confidence: 99%

“…Additionally, compared with those of the vehicle group, the latency times in the hidden platform test were significantly decreased in the TMP group (P<0.05). When the injection administration on the same day as CCI procedure was not applied in the TMP and vehicle groups [TMP (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) and vehicle (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)], a significant difference in latency time in the hidden platform test was not detected. Furthermore, in the spatial probe trial, on PID21 after CCI injury (~2 h after the fifth hidden platform trial), the TMP and vehicle groups demonstrated significantly worse performances than the sham group (P<0.05; Fig.…”

Section: Spatial Learning and Memory Following CCI Injurymentioning

confidence: 99%

“…Among them, 2,3,5,6-tetramethylpyrazine (TMP), which belongs to the alkaloids group (also known as Ligustrazine), is considered to be one of the most important bioactive ingredients from the herb Chuan Xiong, and has been clinically used in the treatment of ischemic brain injury for years (9). In fact, it has been widely studied that TMP may exert explicit neuroprotective roles, such as anti-inflammatory, antioxidant and anti-apoptotic effects, for treating ischemic stroke (10)(11)(12)(13). However, the beneficial effects of TMP on improving the outcomes of TBI have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Tetramethylpyrazine reduces blood-brain barrier permeability associated with enhancement of peripheral cholinergic anti-inflammatory effects for treating traumatic brain injury

Wang

Zhu

Qian

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Traumatic brain injury (TBI) is a diverse group of intracranial injuries resulting from external mechanical insults to the brain. While basic and clinical research for TBI has been conducted for decades, it has not identified cost-effective medical interventions for treating TBI. Tetramethylpyrazine (TMP), which is derived from the Chinese herb, Ligusticum chuanxiong Hort (Chuan Xiong), has been clinically used for treating ischemic brain injury for years. However, whether TMP could provide effective benefits for improving the outcomes following TBI is unknown. In the present study, using controlled cortical impact (CCI) injury to create an animal model of TBI, the potential effects of TMP on improving blood-brain barrier (BBB) permeability in the early phase of the secondary injury, as well as the splenic anti-inflammatory activities, were evaluated. Cognitive functions were also assessed by Morris water maze trials following TBI. Results demonstrated that, at 24 h after CCI injury, BBB permeability was significantly reduced (P<0.05) by the application of TMP. In addition, within 24 h after CCI injury, the plasma levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and protein and mRNA expression levels of IL-1β and TNF-α in the spleen were significantly lowered by TMP (P<0.05). Furthermore, within 24 h after CCI injury, the activation of the splenic anti-inflammatory effects mediated by nicotinic acetylcholine receptor α7 (nAChRa7) stimulation were significantly enhanced by TMP (P<0.05). Additionally, impaired spatial memory acquisition and consolidation were significantly improved by TMP after CCI injury (P<0.05). Together, in light of these data, in the treatment of TBI, TMP could effectively reduce BBB permeability, which may be closely associated with the enhanced splenic anti-inflammatory effects activated by nAChRa7 stimulation, and potentially improve cognitive recovery concerning spatial learning and memory.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Animals and Drug Administrationmentioning

confidence: 99%

Section: Spatial Learning and Memory Following CCI Injurymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tetramethylpyrazine reduces blood-brain barrier permeability associated with enhancement of peripheral cholinergic anti-inflammatory effects for treating traumatic brain injury

Wang

Zhu

Qian

et al. 2017

Experimental and Therapeutic Medicine

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Chinese Herbal Medicines for Neuroprotection in Ischemic Stroke: Promise and Reality

Sucher

Carles

2012

Evidence and Rational Based Research on Chinese Drugs

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Tetramethylpyrazine Analogue CXC195 Ameliorates Cerebral Ischemia–reperfusion Injury by Regulating Endothelial Nitric Oxide Synthase Phosphorylation Via PI3K/Akt Signaling

et al. 2014

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A novel tetramethylpyrazine derivative, CXC195, has been recently shown to protect against cerebral ischemia-reperfusion (I/R) injury. However, the detailed mechanisms underlying the neuroprotection of CXC195 are still unclear. The aim of the present study was to investigate the effects of CXC195 on the phosphorylation of endothelial nitric oxide synthase (eNOS) in response to cerebral I/R and to determine whether phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway might be involved. An in vitro model of oxygen glucose deprivation (OGD) which was performed on primary cultured human aortic endothelial cells (HAECs) and an in vivo middle cerebral artery occlusion (MCAO) model that was performed on Wistar rats were used in this study. CXC195 increased nitric oxide (NO) production and the phosphorylation but not the protein level of eNOS in HAECs subjected to 1 h OGD followed by reperfusion. In addition, CXC195 increased the phosphorylation of Akt; inhibition of PI3K/Akt pathway by a specific inhibitor, wortmannin, suppressed CXC195-induced NO release in HAECs. Consistently, CXC195 treatment significantly restored the phosphorylations of eNOS and Akt in the cortical penumbra of rats subjected to 2 h MCAO followed by reperfusion. Moreover, wortmannin abolished CXC195-induced eNOS phosphorylation and neuroprotection as evidenced by a reversal of the reduction in infarct volume and neurobehavioral outcomes. In conclusion, CXC195 induced phosphorylation of eNOS by activation of PI3K/Akt signaling under pathological cerebral I/R conditions, which provided a novel explanation for the neuroprotective effect of CXC195.

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Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: Therapeutic time window and its mechanism

Cited by 37 publications

References 19 publications

Tetramethylpyrazine reduces blood-brain barrier permeability associated with enhancement of peripheral cholinergic anti-inflammatory effects for treating traumatic brain injury

Tetramethylpyrazine reduces blood-brain barrier permeability associated with enhancement of peripheral cholinergic anti-inflammatory effects for treating traumatic brain injury

Chinese Herbal Medicines for Neuroprotection in Ischemic Stroke: Promise and Reality

Tetramethylpyrazine Analogue CXC195 Ameliorates Cerebral Ischemia–reperfusion Injury by Regulating Endothelial Nitric Oxide Synthase Phosphorylation Via PI3K/Akt Signaling

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