Dengzhanxixin Injection Ameliorates Cognitive Impairment Through a Neuroprotective Mechanism Based on Mitochondrial Preservation in Patients With Acute Ischemic Stroke.

Haiting An,Peng Li,Ying Liang,Wuhai Tao,Zhanjun Zhang,Xiaxia Zhang,Dongfeng Wei,Min Li,Daojun Xie,Kewei Chen

doi:10.3389/fphar.2021.712436

Abstract

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.

Highlights

Stroke is one of the leading causes of death and disability with yet rapid increase (GBD, 2019)
We investigated the efficacy of the DZXI intervention for cognitive impairments in Acute ischemic stroke (AIS) patients and explored the possible mechanism in rats with middle cerebral artery occlusion (MCAO), the model commonly employed in pre-clinical ischemic stroke studies (McCabe et al, 2018)
After DZXI and edaravone treatments, the severity of stroke tested with the NIHSS was attenuated and the neurological deficits assessed by ADL and mRS were alleviated, suggesting that both drugs were effective in AIS treatments

Summary

Introduction

Stroke is one of the leading causes of death and disability with yet rapid increase (GBD, 2019). In China, more than two million new cases of stroke occur annually, and stroke is associated with the highest death and disability-adjusted lifeyears lost among all diseases (Wu et al, 2019). Ischemic stroke accounts for approximately 70% of all incident stroke cases according to a China nation-wide community study (Zhou et al, 2019). Certain infarctions in critically important brain regions may directly cause cognitive impairment in patients with acute ischemic stroke (AIS) (Wang et al, 2021). Cognitive impairment is one of the most common neurological sequelae of ischemic stroke, bitter suffering for patients, as well as a heavy burden for families and the society (Howard, 2016). The daily activities of patients with AIS are seriously affected

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Conclusion