Recent Advances in Chinese Herbal Medicine for Cerebral Ischemic Reperfusion Injury

Cerebral ischemic reperfusion injury (CI/RI) is a critical factor that leads to a poor prognosis in patients with ischemic stroke. It is an extremely complicated pathological process that is clinically characterized by high rates of disability and mortality. Current available treatments for CI/RI, including mechanical and drug therapies, are often accompanied by significant side effects. Therefore, it is necessary to discovery new strategies for treating CI/RI. Many studies confirm that Chinese herbal medicine (CHM) was used as a potential drug for treatment of CI/RI with the advantages of abundant resources, good efficacy, and few side effects. In this paper, we investigate the latest drug discoveries and advancements on CI/RI, make an overview of relevant CHM, and systematically summarize the pathophysiology of CI/RI. In addition, the protective effect and mechanism of related CHM, which includes extraction of single CHM and CHM formulation and preparation, are discussed. Moreover, an outline of the limitations of CHM and the challenges we faced are also presented. This review will be helpful for researchers further propelling the advancement of drugs and supplying more knowledge to support the application of previous discoveries in clinical drug applications against CI/RI.

Balloon expandable Stent utility for early Secondary Prevention of new Cerebral Ischemic events Caused by Intracranial Atherosclerotic Stenosis. Technical Nuances

Objective: Recurrent cerebral ischemic events are estimated to appear in between 12-15% of symptomatic intracranial atherosclerotic disease (ICAD), regardless of the use of leading pharmacological therapies. Balloon expandable stent (balloon mounted coronary stent) could represent a feasible alternative in this disease’s treatment. This study pretends to report the balloon-expandable placement experience in our center. Materials and Methods: A unicentric retrospective study dated between September 2009 and March 2018 was conducted. Patients previously diagnosed with ICAD and symptomatic stenosis treated with balloon-expandable stent were included. Clinical features, morbidity, mortality, short and long-term evolution, and pre-and post-treatment angiographic features were analyzed, as well as a mean 8 years-period follow-up. Data are presented as means, frequencies, and percentages for categorical variables, and ranks for continuous variables. Statistical analysis was carried by IBM SPSS Statistics Base V22.0 (IBM Corporation, Mexico). A Wilcoxon Signed-rank test statistical analysis was performed. Statistical significance was considered when a p-value lesser than 0.05 was measured for every result. Results: A total of 6 patients with 7 affected vessels were treated, with an average age of 62.7 years. Affected and treated vessels were located in the Internal Carotid Artery (ICA) segment in 42.9%, Vertebral Artery (VA) V4 segment in 14.3%, Middle Cerebral Artery (MCA) M1 segment in 28.5%, and Posterior Cerebral Artery (PCA) P1 segment in 14.3%. The incidence of peri-operatory thrombotic events was 0%. Intracranial hemorrhage presented in 0% of cases. Recurrent ischemic or thrombotic events were not reported in a 97-months mean follow-up. 71.4% of patients scored ≤2 in the modified Rankin Score (mRS) pre-treatment, in a 90 day and 12-month follow-up. 100% presented a favorable evolution with mRS ≤2. Restenosis cases were not reported in radiologic control and retreatment was not needed in a 97-month mean follow-up. Conclusions: This study suggests that balloon-expandable stent therapy with some technical endovascular variants for its navigation and placement could be a safe and effective alternative in the treatment of ICAD as a means of cerebral ischemic event early secondary prevention. We propose to consider not to limit endovascular treatment exclusively to those symptomatic ICAD patients refractory to medical-exclusive treatment, as a means to reduce the risk of presenting a new neurological deficit. Further expanded clinical trials are needed to confirm these findings and the advantage of this kind of stents against other kinds reported in the literature.

Hsp47 Inhibitor Col003 Attenuates Collagen-Induced Platelet Activation and Cerebral Ischemic–Reperfusion Injury in Rats

Ischemic stroke is a major type of stroke worldwide currently without effective treatment, although antiplatelet therapy is an existing option for it. In previous studies, heat shock protein 47 (Hsp47) was found to be expressed on the surface of human and mice platelets and to strengthen the interaction between platelets and collagen. In recent years, Col003 was discovered to inhibit the interaction of Hsp47 with collagen. We evaluated whether the Hsp47 inhibitor Col003 is a promising therapeutic agent for ischemic stroke. Here, we first verified that Hsp47 is also expressed on the surface of rat platelets, and its inhibitor Col003 significantly inhibited thrombus formation in the FeCl3-induced rat carotid arterial thrombus model. Both Col003 and clopidogrel did not alter the bleeding time or coagulation parameters, while aspirin increased the tail-bleeding time (p < 0.05). The low cytotoxicity level of Col003 to rat platelets and human liver cells was similar to those of aspirin and clopidogrel. Col003 inhibited collagen-induced platelet aggregation, adhesion, [Ca2+]i mobilization, P-selectin expression, reactive oxygen species production and the downstream signal pathway of collagen receptors. The results of the middle cerebral artery occlusion model indicated that Col003 has a protective effect against cerebral ischemic–reperfusion injury in rats. The Hsp47 inhibitor Col003 exerted antiplatelet effect and protective effect against brain damage induced by ischemic stroke through the inhibition of glycoprotein VI (GPVI)and mitogen-activated protein kinase (MAPK) signaling events, which might yield a new antiplatelet agent and strategy to treat ischemic stroke.