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

2022 ◽  
Vol 12 ◽  
Author(s):  
Shuang Wu ◽  
Chengwei Liang ◽  
Xiaoyun Xie ◽  
Haiping Huang ◽  
Jinfeng Fu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Bleeding Time ◽  
Mapk Signaling ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
Rat Platelets

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.

scholarly journals Protective Effect of Pharmacological Preconditioning of Total Flavones of Abelmoschl Manihot on Cerebral Ischemic Reperfusion Injury in Rats

2007 ◽  
Vol 35 (04) ◽  
pp. 653-661 ◽  
Author(s):  
Ji-Yue Wen ◽  
Zhi-Wu Chen
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inos Mrna ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Infarction Volume ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion ◽  
Pharmacological Preconditioning

The present study was to investigate the effect of pharmacological preconditioning of total flavones of Abelmoschl Manihot (TFA) on cerebral ischemic reperfusion injury in rats. Rat cerebral ischemia/reperfusion injury was induced by occluding the right middle cerebral artery (MCA). The infarct size was determined by staining with 2,3,5-triphenyl tetrazalium chloride (TTC). The serum malonaldehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) levels were measured by using spectrophotometry; Inducible NO synthase (iNOS) mRNA expression was detected by RT-PCR method. The percentage of cerebral infarction volume was 28.1 ± 0.8 in the model group, while TFA or nimodipine (Nim) pretreatment 36 hours prior to the ischemic insult significantly decreased the infarction volume. Increases of serum LDH activity and MDA level were observed after ischemia/reperfusion, but these changes were inhibited in rats pretreated with either TFA (20, 40, 80, 160 mg/kg) or Nim, indicating a delayed protective effect of TFA preconditioning on cerebral ischemic reperfusion injury. In addition, the serum NO level and the cerebral iNOS mRNA were up-regulated, suggesting a possible mechanism for the protective effect of TFA pretreatment on cerebral ischemic reperfusion injury.

scholarly journals PROTECTIVE EFFECT OF ETHANOLIC EXTRACT FROM THE ROOT OF ARGYREIA SPECIOSA AGAINST GLOBAL CEREBRAL ISCHEMIC REPERFUSION INJURY IN RATS

2018 ◽  
Vol 8 (6) ◽  
pp. 8-15
Author(s):  
Bhagat Singh Jaiswal ◽  
Mukul Tailang
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ethanolic Extract ◽  
Cerebral Stroke ◽  
Sham Control ◽  
Ischemic Reperfusion Injury ◽  
Ischemic Reperfusion ◽  
Group I ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion

Cerebral stroke is the principal reason of death without effective treatment in the world and recognized as the common cause of disability. Argyreia speciosa (Linn.f.) (Convolvulaceae, Synonyms: Argyreia nervosa) is widely distributed plant species in India. It is commonly known as Elephant creeper and Vryddhadaru. A. speciosa is a very valuable plant in the Ayurvedic system. In 'Rasayan' drug it has been used for the treatment of various neurological diseases. Its root taste is bitter and having the multiple uses like as a brain tonic, nootropic, anti-anxiety and anticonvulsant activity. The current study, plan to investigate the neuroprotective effect of ethanolic extract of A. speciosa root (ASEE) in a validate rat model of stroke known as global cerebral ischemic reperfusion injury (GCIRI). We divided 36 male Wistar rats to six experimental groups (n= 6). The group-I considered as sham control (no GCIRI), Group-II saline treated GCIRI, Group-III, IV, and V received ASEE (100, 200 and 400 mg/kg, p.o.) for 7 days prior to the induction of GCIRI while Group-VI termed as standard and it received quercetin (20 mg/kg, i.p.) 30 min prior induction of GCIRI. GCIRI produced the significant neurological deficit, sensorimotor dysfunction, decrease neurobehavioral parameters, increased cerebral infarction area and brain edema as compared with sham control rats. Seven days of pretreatment with ASEE markedly attenuates all the changes caused by GCIRI to the normal level. Our results proved that ASEE possess the protective effect on GCIRI induced stroke and aforementioned neuroprotection may be due to its antioxidant and anti-inflammatory property. Keywords: Brain stroke, BCCAO, Antioxidants, Neuroprotection, Argyreia speciosa

Cerebral Ischemic Reperfusion Injury Following Recanalization of Large Vessel Occlusions

Neurosurgery ◽  
2017 ◽  
Vol 82 (6) ◽  
pp. 781-789 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
Krishna Amuluru ◽  
William Roth ◽  
Rolla Nuoman ◽  
Mohammad El-Ghanem ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Reperfusion Injury ◽  
Large Artery ◽  
Stroke Patients ◽  
Ischemic Reperfusion Injury ◽  
Stroke Treatment ◽  
Ischemic Reperfusion ◽  
Cerebral Ischemic ◽  
Cerebral Ischemic Reperfusion

Abstract Although stroke has recently dropped to become the nation's fifth leading cause of mortality, it remains the top leading cause of morbidity and disability in the US. Recent advances in stroke treatment, including intravenous fibrinolysis and mechanical thromboembolectomy, allow treatment of a greater proportion of stroke patients than ever before. While intra-arterial fibrinolysis with recombinant tissue plasminogen is an effective for treatment of a broad range of acute ischemic strokes, endovascular mechanical thromboembolectomy procedures treat severe strokes due to large artery occlusions, often resistant to intravenous drug. Together, these procedures result in a greater proportion of revascularized stroke patients than ever before, up to 88% in 1 recent trial (EXTEND-IA). Subsequently, there is a growing need for neurointensivists to develop more effective strategies to manage stroke patients following successful reperfusion. Cerebral ischemic reperfusion injury (CIRI) is defined as deterioration of brain tissue suffered from ischemia that concomitantly reverses the benefits of re-establishing cerebral blood flow following mechanical or chemical therapies for acute ischemic stroke. Herein, we examine the pathophysiology of CIRI, imaging modalities, and potential neuroprotective strategies. Additionally, we sought to lay down a potential treatment approach for patients with CIRI following emergent endovascular recanalization for acute ischemic stroke.

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