scholarly journals The Neuroprotective Effect of l-Borneolum on Cerebral Ischemic Stroke by Regulating Dll4/Notch1 Pathway

2021 ◽  
Author(s):  
Taiwei Dong ◽  
Nian Chen ◽  
Rong Ma ◽  
Qian Xie ◽  
Xiaoqing Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Immunohistochemical Method ◽  
Triphenyltetrazolium Chloride ◽  
Severity Scores ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Abstract Aiml-Borneolum is a monoterpene compound witch deserved from Blumea balsamifera (L.) DC, this study aimed to investigate the potential mechanism of l-borneolum on cerebral ischemic stroke (CIS) rats and provide evidence for the development of l-borneolum in CIS.MethodsPermanent middle cerebral artery occlusion (pMCAO) model rats were applied to this study. Neurological function was assessed by modified neurological severity scores (mNSS) and Longa neurological function scoring methods. The pathological changes of cerebral tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE) staining. Ultrastructure of blood brain barrier (BBB) was observed by transmission electron microscopy. Additionally, the expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex were determined by Western blotting (WB) while expression of caspase 3 were determined by immunohistochemical method (IHC). Resultsl-Borneolum improved neurological function in a dose-dependently. l-Borneolum significantly alleviated brainstem edema and inflammation, as well as improved the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum substantially decreased the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while decreased the level of Caspase-3 in the cortex of rats. Conclusionsl-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway.

scholarly journals Based on Dll4/Notch1 Signaling Pathway to Elucidate the Therapeutic Effect and Mechanism of L-borneolum on Cerebral Ischemic Stroke Rats

2021 ◽  
Author(s):  
Taiwei Dong ◽  
Nian Chen ◽  
Rong Ma ◽  
Qian Xie ◽  
Xiaoqing Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Neurological Function ◽  
Immunohistochemical Method ◽  
Research Progress ◽  
Notch1 Signaling ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Notch1 Signaling Pathway

Abstract Background: The current research progress suggests that a single therapy may not be ideal means for complex cerebral ischemic stoke (CIS). l-Borneolum is the crystallization of fresh leaves of Blumea balsamifera (L.) DC, we have found that l-borneolum plays a best anti-cerebral ischemic effect than d-borneolum or synthetic borneolum. However, the mechanism is needed to be explored in depth. Therefore, based on comprehensive approach that combines molecular docking technology and molecular biology, this stiudy aimed to investigate the potential mechanism of l-borneolum on CIS rats and provide scientific evidence for the treatment of l-borneolum in CIS.Methods: Cerebral ischemic stroke (CIS) rats with permanent middle cerebral artery occlusion (pMCAO) were applied to this study. The modified neurological severity scores (mNSS) and Longa neurological function scoring methods were used to assess the neurobehavioral scores. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to evaluate pathological changes of cerebral tissue. Ultrastructure of cortical capillary and blood-brain barrier (BBB) in rats were observed by transmission electron microscopy. In addition, the protein expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex of rats were determined by Western blotting (WB). The protein contents of Caspase 3 in the cortex of rats were determined by immunohistochemical method (IHC). Results: l-Borneolum could prolong the resuscitation time, reduce the abnormal increased rectal temperature, improve neurological function in a dose-dependently. Additionally, l-borneolum could significantly alleviate brainstem edema and inflammation, as well as improve the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum could substantially decrease the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while it decreased the level of Caspase-3 in the cortex of rats. Conclusions: l-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway, l-borneolum might be a good complementary agent for CIS.

cGAS-STING signaling regulates control of microglia polarization in cerebral ischemic stroke

2020 ◽  
Author(s):  
Guoliang Jiang ◽  
Xinglong Yang ◽  
Houjun Zhou ◽  
Jiang Long ◽  
Linming Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Inflammatory Response ◽  
Cell Model ◽  
Glucose Deprivation ◽  
Artery Occlusion ◽  
Ht22 Cells ◽  
Bv2 Microglia ◽  
Cerebral Ischemic Stroke ◽  
Sting Pathway ◽  
Cerebral Ischemic

Abstract Background Cerebral ischemic stroke is a highly debilitating disease, in which inflammation is well document to play a pivotal role in its pathophysiology. Microglia are the the major immuncompetent cells of the brain involved in different neuropathologies. Recent discovery of cyclic GMP-AMP synthase(cGAS) activation and its induction of the downstream signaling protein stimulator of interferon genes (STING) is increasingly recognized as a crucial determinant of neuropathophysiology. Although cGAS-STING pathway has been reported to play an important role in inflammatory response in myocardial infarction (MI), its mechanism in inflammatory response in ischemic stroke (IS) has remained to be fully explored.Methods In light of the above, this study sought to explore the roles of cGAS-STING pathway in inflammatory reaction in IS. It is hoped that the results would provide new insights for designing of therapeutic strategies targeting at IS. We used HT22 cells to establish an oxygen-glucose deprivation (OGD) cell model. The supernatant derived from this and which contained OGD-induced DAMPs(OIDs) was used to stimulate the BV2 microglia. Additionally, we used siRNA technology to interfere with cGAS gene expression to observe changes in downstream cytokines. Furthermore, we established middle cerebral artery occlusion (MCAO) mouse model and performed cGAS-siRNA lentivirus infection to further elucidate the mechanism of cGAS-STING pathway in vivo.Results We show here that OIDs strongly activated the cGAS-STING pathway and triggered accumulation of a plethora of proinflammatory factors in activated Microglia. Of note, the cascade reaction was successfully inhibited by cGAS-siRNA. Furthermore, we extended the study of cGAS-STING in a mouse MCAO model, which showed that inhibiting cGAS-STING pathway can effectively diminish MIDs(MCAO-induced DAMPs)-induced neuronal apoptosis and ultimately functional improvement.Conclusion The present results have shown GAS-STING signaling pathway controls the polarity transformation of microglia. The underlying mechanisms of cGAS-STING triggering microglial inflammatory response is now better clarified which made the pathway a potential therapeutic target of IS.

scholarly journals Benzoinum exerts NVU protective effect by inhibiting cell apoptosis in cerebral ischemia rats

2020 ◽  
Author(s):  
Qian Xie ◽  
Rong Ma ◽  
Xiaoqing Guo ◽  
Hai Chen ◽  
Jian Wang
Keyword(s):  
Ischemic Stroke ◽  
Protective Effect ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Cerebrovascular Diseases ◽  
Neuroprotective Activity ◽  
Stroke Therapy ◽  
Function Score ◽  
Cerebral Ischemic

Abstract Background Benzoinum (Styraceae) is a traditional Chinese medicine known to treat stroke and other cardio-cerebrovascular diseases for thousands of years. Benzoinum also proved to have diverse pharmacological activity, but the neuroprotection mechanism about apoptosis in ischemic stroke were not found. This study is to investigate the NVU protective effect and mechanisms of benzoinum on cerebral ischemic rats. Methods The neuroprotective activity of benzoinum against MCAO induced cerebral ischemic injury. Neurological scores, TTC staining, HE staining were conducted to evaluate neurological damage. Infarction rate and DCI were calculated. The ultrastructure of neuron and BBB was observed by TEM. Immunohistochemistry and RT-PCR were used to detect the Bax, Bcl-2, Caspase 3 expression. In addition, Claudin 5 also was detected by immunohistochemistry. Results The findings shown that benzoinum could significantly improve the neurological function score, reduce the cerebral infarction rate and DCI. Furthermore, benzoinum alleviated pathomorphological change and apoptosis in brain tissue of MCAO rats. The results of TEM and claudin 5 expression of immunohistochemistry showed that benzoinum could play a neuroprotective effect in NVU. Besides, benzoinum enhanced Bcl2, reduced Bax and Bax/Bcl-2, Caspase 3, suggesting benzoinum provided neuroprotective effect by inhibited cell apoptosis. Conclusion Benzoinum could play a neuroprotective role and regulate apoptosis to repair and stabilize NVU. Our present findings provide a promising medicine for treatment of ischemic stroke therapy.

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