scholarly journals Oxidative Stress, Inflammation, and Autophagy: Potential Targets of Mesenchymal Stem Cells-Based Therapies in Ischemic Stroke

2021 ◽  
Vol 15 ◽  
Author(s):  
Jialin He ◽  
Jianyang Liu ◽  
Yan Huang ◽  
Xiangqi Tang ◽  
Han Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Blood Flow ◽  
Mesenchymal Stem Cells ◽  
Ischemic Stroke ◽  
Ischemic Injury ◽  
Cerebral Injury ◽  
Inflammatory Activity ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Ischemic stroke is a leading cause of death worldwide; currently available treatment approaches for ischemic stroke are to restore blood flow, which reduce disability but are time limited. The interruption of blood flow in ischemic stroke contributes to intricate pathophysiological processes. Oxidative stress and inflammatory activity are two early events in the cascade of cerebral ischemic injury. These two factors are reciprocal causation and directly trigger the development of autophagy. Appropriate autophagy activity contributes to brain recovery by reducing oxidative stress and inflammatory activity, while autophagy dysfunction aggravates cerebral injury. Abundant evidence demonstrates the beneficial impact of mesenchymal stem cells (MSCs) and secretome on cerebral ischemic injury. MSCs reduce oxidative stress through suppressing reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and transferring healthy mitochondria to damaged cells. Meanwhile, MSCs exert anti-inflammation properties by the production of cytokines and extracellular vesicles, inhibiting proinflammatory cytokines and inflammatory cells activation, suppressing pyroptosis, and alleviating blood–brain barrier leakage. Additionally, MSCs regulation of autophagy imbalances gives rise to neuroprotection against cerebral ischemic injury. Altogether, MSCs have been a promising candidate for the treatment of ischemic stroke due to their pleiotropic effect.

Treatment Efficacy with Bone Marrow Derived Mesenchymal Stem Cells and Minocycline in Rats After Cerebral Ischemic Injury

2012 ◽  
Vol 9 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Sule Bilen ◽  
Ferda Pinarli ◽  
Fikri Ak ◽  
Ersin Fadillioglu ◽  
Aynur Albayrak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Treatment Efficacy ◽  
Ischemic Injury ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

scholarly journals Salidroside-pretreated mesenchymal stem cells contribute to neuroprotection in cerebral ischemic injury in vitro and in vivo

2020 ◽  
Author(s):  
Liping Zhou ◽  
Panpan Yao ◽  
Lixia Jiang ◽  
Zhaoyun Wang ◽  
Xiaohe Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effect ◽  
Ischemic Injury ◽  
Cell Counting ◽  
Neuroprotective Effects ◽  
Therapeutic Efficiency ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Abstract Background: Mesenchymal stem cells (MSCs) are considered a promising tool for treating cerebral ischemic injury. However, their poor survival after transplantation limits their therapeutic effect and applications. Salidroside has been reported to exert potent cytoprotective and neuroprotective effects. This study aimed to investigate whether salidroside could improve MSC survival under hypoxic-ischemic conditions and, subsequently, alleviate cerebral ischemic injury in a rat model.Methods: MSCs were pretreated by salidroside under hypoxic-ischemic conditions. The cell proliferation, migratory capacity, and apoptosis were evaluated by means of Cell Counting Kit (CCK)-8, transwell assay, and flow cytometry. MSCs pretreated with salidroside were transplanted into the rats subsequent to middle cerebral artery occlusion. The grip strength, 2,3,5-triphenyltetrazolium chloride, and hematoxylin-eosin staining were used to analyze the therapeutic efficiency and pathological changes. The mature neuron marker NeuN and astrocyte marker GFAP in the focal area were detected by immunofluorescence.Results: These results indicated that salidroside promoted the proliferation, migration and reduced apoptosis of MSCs under hypoxic-ischemic conditions. In vivo experiments revealed that transplantation of salidroside-pretreated MSCs strengthened the therapeutic efficiency by enhancing neurogenesis and inhibiting neuroinflammation in the hippocampal CA1 area after ischemia.Conclusion: Our results suggest that pretreatment with salidroside could be an effective strategy to enhance the cell survival rate and the therapeutic effect of MSCs in treating cerebral ischemic injury.

scholarly journals Intradialytic Cerebral Hypoperfusion as Mechanism for Cognitive Impairment in Patients on Hemodialysis

2019 ◽  
Vol 30 (11) ◽  
pp. 2052-2058 ◽  
Author(s):  
Dawn F. Wolfgram
Keyword(s):  
Cognitive Impairment ◽  
Cerebral Perfusion ◽  
Ischemic Injury ◽  
Hemodialysis Patients ◽  
Cognitive Outcomes ◽  
Cerebral Injury ◽  
Cerebral Hypoperfusion ◽  
Increased Risk ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

The high frequency of cognitive impairment in individuals on hemodialysis is well characterized. In-center hemodialysis patients are disproportionately affected by cognitive impairment compared with other dialysis populations, identifying hemodialysis itself as a possible factor. The pathophysiology of cognitive impairment has multiple components, but vascular-mediated cerebral injury appears to contribute based on studies demonstrating increased cerebral ischemic lesions and atrophy in brain imaging of patients on hemodialysis. Patients on hemodialysis may be at increased risk for cerebral ischemic injury disease due to vasculopathy associated with ESKD and from their comorbid diseases, such as hypertension and diabetes. This review focuses on the intradialytic cerebral hypoperfusion that can occur during routine hemodialysis due to the circulatory stress of hemodialysis. This includes a review of current methods used to monitor intradialytic cerebral perfusion and the structural and functional cognitive outcomes that have been associated with changes in intradialytic cerebral perfusion. Monitoring of intradialytic cerebral perfusion may become clinically relevant as nephrologists try to avoid the cognitive complications seen with hemodialysis. Identifying the appropriate methods to assess risk for cerebral ischemic injury and the relationship of intradialytic cerebral hypoperfusion to cognitive outcomes will help inform the decision to use intradialytic cerebral perfusion monitoring in the clinical setting as part of a strategy to prevent cognitive decline.

scholarly journals Borneol for Regulating the Permeability of the Blood-Brain Barrier in Experimental Ischemic Stroke: Preclinical Evidence and Possible Mechanism

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Zi-xian Chen ◽  
Qing-qing Xu ◽  
Chun-shuo Shan ◽  
Yi-hua Shi ◽  
Yong Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Ischemic Injury ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Glycoprotein P ◽  
Blood Brain ◽  
Cerebral Ischemic Injury ◽  
Bbb Permeability ◽  
Cerebral Ischemic

Borneol, a natural product in the Asteraceae family, is widely used as an upper ushering drug for various brain diseases in many Chinese herbal formulae. The blood-brain barrier (BBB) plays an essential role in maintaining a stable homeostatic environment, while BBB destruction and the increasing BBB permeability are common pathological processes in many serious central nervous system (CNS) diseases, which is especially an essential pathological basis of cerebral ischemic injury. Here, we aimed to conduct a systematic review to assess preclinical evidence of borneol for experimental ischemic stroke as well as investigate in the possible neuroprotective mechanisms, which mainly focused on regulating the permeability of BBB. Seven databases were searched from their inception to July 2018. The studies of borneol for ischemic stroke in animal models were included. RevMan 5.3 was applied for data analysis. Fifteen studies investigated the effects of borneol in experimental ischemic stroke involving 308 animals were ultimately identified. The present study showed that the administration of borneol exerted a significant decrease of BBB permeability during cerebral ischemic injury according to brain Evans blue content and brain water content compared with controls (P<0.01). In addition, borneol could improve neurological function scores (NFS) and cerebral infarction area. Thus, borneol may be a promising neuroprotective agent for cerebral ischemic injury, largely through alleviating the BBB disruption, reducing oxidative reactions, inhibiting the occurrence of inflammation, inhibiting apoptosis, and improving the activity of lactate dehydrogenase (LDH) as well as P-glycoprotein (P-GP) and NO signaling pathway.

scholarly journals Deletion of Aldose Reductase Leads to Protection against Cerebral Ischemic Injury

2007 ◽  
Vol 27 (8) ◽  
pp. 1496-1509 ◽  
Author(s):  
Amy CY Lo ◽  
Alvin KH Cheung ◽  
Victor KL Hung ◽  
Chung-Man Yeung ◽  
Qing-Yu He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Aldose Reductase ◽  
Therapeutic Potential ◽  
Ischemic Injury ◽  
Adenosine Diphosphate ◽  
Polyol Pathway ◽  
Neurological Deficits ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Transient Focal Ischemia

Previously, we reported that transgenic mice overexpressing endothelin-1 in astrocytes showed more severe neurological deficits and increased infarct after transient focal ischemia. In those studies, we also observed increased level of aldose reductase (AR), the first and rate-limiting enzyme of the polyol pathway, which has been implicated in osmotic and oxidative stress. To further understand the involvement of the polyol pathway, the mice with deletion of enzymes in the polyol pathway, AR, and sorbitol dehydrogenase (SD), which is the second enzyme in this pathway, were challenged with similar cerebral ischemic injury. Deletion of AR-protected animals from severe neurological deficits and large infarct, whereas similar protection was not observed in mice with SD deficiency. Most interestingly, AR−/− brains showed lowered expression of transferrin and transferrin receptor with less iron deposition and nitrotyrosine accumulation. The protection against oxidative stress in AR−/− brain was also associated with less poly(adenosine diphosphate-ribose) polymerase (PARP) and caspase-3 activation. Pharmacological inhibition of AR by Fidarestat also protected animals against cerebral ischemic injury. These findings are the first to show that AR contributes to iron- and transferrin-related oxidative stress associated with cerebral ischemic injury, suggesting that inhibition of AR but not SD may have therapeutic potential against cerebral ischemic injury.

scholarly journals PGE2 signaling via the neuronal EP2 receptor increases injury in a model of cerebral ischemia

2019 ◽  
Vol 116 (20) ◽  
pp. 10019-10024 ◽  
Author(s):  
Qingkun Liu ◽  
Xibin Liang ◽  
Qian Wang ◽  
Edward N. Wilson ◽  
Rachel Lam ◽  
...  
Keyword(s):  
Ischemic Injury ◽  
Myeloid Cell ◽  
Cell Types ◽  
Receptor Expression ◽  
Cerebral Injury ◽  
Stroke Severity ◽  
Cell Trafficking ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic ◽  
Ep2 Receptor

The inflammatory prostaglandin E2 (PGE2) EP2 receptor is a master suppressor of beneficial microglial function, and myeloid EP2 signaling ablation reduces pathology in models of inflammatory neurodegeneration. Here, we investigated the role of PGE2 EP2 signaling in a model of stroke in which the initial cerebral ischemic event is followed by an extended poststroke inflammatory response. Myeloid lineage cell-specific EP2 knockdown in Cd11bCre;EP2lox/lox mice attenuated brain infiltration of Cd11b+CD45hi macrophages and CD45+Ly6Ghi neutrophils, indicating that inflammatory EP2 signaling participates in the poststroke immune response. Inducible global deletion of the EP2 receptor in adult ROSA26-CreERT2 (ROSACreER);EP2lox/lox mice also reduced brain myeloid cell trafficking but additionally reduced stroke severity, suggesting that nonimmune EP2 receptor-expressing cell types contribute to cerebral injury. EP2 receptor expression was highly induced in neurons in the ischemic hemisphere, and postnatal deletion of the neuronal EP2 receptor in Thy1Cre;EP2lox/lox mice reduced cerebral ischemic injury. These findings diverge from previous studies of congenitally null EP2 receptor mice where a global deletion increases cerebral ischemic injury. Moreover, ROSACreER;EP2lox/lox mice, unlike EP2−/− mice, exhibited normal learning and memory, suggesting a confounding effect from congenital EP2 receptor deletion. Taken together with a precedent that inhibition of EP2 signaling is protective in inflammatory neurodegeneration, these data lend support to translational approaches targeting the EP2 receptor to reduce inflammation and neuronal injury that occur after stroke.

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