Topic: Mechanism Study of Acupuncture Extending the rt-PA Thrombolytic Time Window of Cerebral Ischemic Stroke

Zhihui Zhang


Ph.D. student in the Department of Acupuncture and Tuina at Nanjing University of Chinese Medicine, supervised by Professor Guangxia Ni. The main research interest is the effect and mechanism of acupuncture combined with medicine for cerebral infarction. B.Sc. in TCM was obtained from Anhui University of Chinese Medicine and M.Sc. in acupuncture and moxibustion was from Nanjing University of Chinese Medicine. As the first author, I have published one SCI paper and one Chinese core journal. As the co-author, I have published five papers on the mechanism of acupuncture for ischemic stroke. I have been involved in three projects funded by the National Natural Science Foundation of China, one project funded by the Postgraduate Research and Practice Innovation Program of Jiangsu Province, and attended many academic conferences.


The rt-PA-mediated thrombolysis was the best treatment for the ultra-early stage of cerebral ischemic stroke (CIS). However, the very short time window of thrombolysis (3-4.5h) make it difficult to implement in clinical practice due to the thrombolytic complications, such as brain edema and hemorrhagic transformation (HT), particularly when delayed thrombolysis. Therefore, it is critical to find a therapeutic strategy to reduce complications and extend the thrombolytic time window.
Acupuncture, as a traditional medical treatment in China, is considered as an effective treatment for CIS. Our previous studies indicated that acupuncture intervention can reduce infarct volume, attenuate brain edema, and improve neurological functions in animal models of ischemic stroke. In addition, our systematic review and meta-analysis added to the clinical evidence that acupuncture combined with thrombolysis has a better effect on improving clinical efficacy rate, NIHSS score, Barthel index and C-reactive protein level when compared with thrombolysis alone. So the present study was conducted to test the hypothesis that acupuncture extends the therapeutic time window of rt-PA for ischemic stroke in a male rat model of embolic stroke.
A male rat model of embolic stroke was adopted in our study, and acupuncture treatment was performed on 2 hours after model completion. Neurological function, infarct volume, BBB permeability, brain edema, and HT were assessed at different thrombolytic time beyond 4.5 h. Then, by using molecular biological methods, ERK1/2 signaling pathway related indicators mRNA , protein expression in ischemic penumbra, and activity of MMP-9 were tested. On the multiple perspectives, it could provide theoretical support for thrombolytic therapy, and instruction to the clinical.
In conclusion, acupuncture potentially represents an effective adjunct method to minimize associated complications with delayed thrombolysis and extend the therapeutic time window of rt-PA to 6 h in a male rat model of embolic stroke. This neuroprotective effect may be mediated by the inhibition of the ERK1/2-MMP9 pathway and alleviation of the destruction of the BBB.


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