scholarly journals A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Chao Zhang ◽  
Yan Wen ◽  
Xiaonong Fan ◽  
Sha Yang ◽  
Guang Tian ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Microarray Analysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Artery Occlusion ◽  
Pathological Process ◽  
Ischemic Brain ◽  
Acupuncture Intervention ◽  
Polymerase Chain ◽  
Cerebral Artery Occlusion

Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo) rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, includingTph1andOlr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR). Upregulation ofTph1and downregulation ofOlr883indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

scholarly journals Image-based stroke rat brain atrophy volume and infarct volume computation

2020 ◽  
Vol 76 (12) ◽  
pp. 10090-10121
Author(s):  
Yung-Kuan Chan ◽  
Chun-Fu Hong ◽  
Meng-Hsiun Tsai ◽  
Ya-Lan Chang ◽  
Ping-Hsuan Sun
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Brain Slice ◽  
Infarct Volume ◽  
Brain Slices ◽  
Artery Occlusion ◽  
Tetrazolium Chloride ◽  
Rat Brain Slice ◽  
Cerebral Artery Occlusion ◽  
The Brain

Abstract Stroke is one of the leading causes of death as well as results in a massive economic burden for society. Stroke is a cerebrovascular disease mainly divided into two types: ischemic stroke and hemorrhagic stroke, which, respectively, refer to the partial blockage and bleeding inside brain blood vessels. Both stroke types lead to nutrient and oxygen deprivation in the brain, which ultimately cause brain damage or death. This study focuses on ischemic stroke in rats with middle cerebral artery occlusion (MCAO) as experimental subjects, and the volumes of infarct and atrophy are calculated based on the brain slice images of rat brains stained with 2,3,5-triphenyl tetrazolium chloride. In this study, a stroke rat brain infarct and atrophy volumes computation system (SRBIAVC system) is developed to segment the infarcts and atrophies from the rat brain slice images. Based on the segmentation results, the infarct and atrophy volumes of a rat brain can be computed. In this study, 168 images of brain slices cut from 28 rat brains with MCAO are used as the test samples. The experimental results show that the segmentation results obtained by the SRBIAVC system are close to those obtained by experts.

Abstract WP134: 3K3A-APC Protects Pericyte-deficient Mice From Ischemic Brain Injury

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yaoming Wang ◽  
Mikko Huuskonen ◽  
Axel Montagne ◽  
Berislav Zlokovic
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Activated Protein C ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Neuroprotective Effects ◽  
Ischemic Brain ◽  
Functional Deficits ◽  
Favorable Safety ◽  
Cerebral Artery Occlusion

Pericytes play a key role in maintaining the blood-brain barrier (BBB) integrity. BBB disruption occurs during early stages after ischemic stroke. However, the role of pericytes in the pathogenesis of ischemic stroke remains still understudied. 3K3A-APC, a recombinant variant of activated protein C, has shown benefits in preclinical models of ischemic stroke and has favorable safety profile and reduces hemorrhage in Phase 2 study in ischemic stroke patients (RHAPSODY). In the present study, we used PDGFRβ heterozygous knockout (PDGFRβ+/-) mice to investigate the effects of pericyte deficiency on ischemic brain injury using transient proximal middle cerebral artery occlusion (tMCAO). Additionally, we investigated the effects of 3K3A-APC therapy (0.2mg/kg i.v. 4h after stroke) in this model. Compared to controls, pericyte deficiency in PDGFRβ+/- mice resulted in ~35% increase in the infarct and edema volumes, reduction in pericyte coverage from 58% to 25%, and increased IgG and fibrin deposition suggesting accelerated BBB breakdown 24h after stroke. Additionally, PDGFRβ+/- mice showed by 36% more degenerating Fluoro-Jade+ neurons and exhibited accelerated neurobehavioral abnormalities. 3K3A-APC improved neuropathological changes and functional deficits. Our results suggest that pericyte deficiency worsens brain damage and functional outcome after ischemic stroke in mice suggesting that pericytes may play an important role in protecting brain from post-ischemic. We also suggests that 3K3A-APC protects pericyte function in stroked mice which could contribute to its overall neuroprotective effects.

scholarly journals Silencing of lncRNA XLOC_035088 Protects Middle Cerebral Artery Occlusion-Induced Ischemic Stroke by Notch1 Signaling

2020 ◽  
Vol 80 (1) ◽  
pp. 60-70
Author(s):  
Miao Chen ◽  
Feng Wang ◽  
Hairong Wang
Keyword(s):  
Ischemic Stroke ◽  
Brain Injury ◽  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Hippocampal Neurons ◽  
Artery Occlusion ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Cerebral Artery Occlusion

Abstract Ischemic stroke represents one of the leading causes of mortality worldwide and especially in developing countries. It is crucial for finding effective therapeutic targets that protect the brain against ischemic injury. Long noncoding RNAs (lncRNAs) have emerged as major regulators of neurological diseases, and clarifying their roles in cerebral ischemic injury may provide novel targets for the treatment of ischemic stroke. We aimed to investigate the role of lncRNA-XLOC_035088 in middle cerebral artery occlusion (MCAO)-induced rat brain injury and oxygen-glucose deprivation (OGD)-reperfusion treated hippocampal neurons. In our findings, we found that XLOC_035088 expression was significantly upregulated in OGD-reperfusion treated hippocampal neurons and in different brain regions of MCAO-treated rats. XLOC_035088 silencing protected against MCAO-induced ischemic brain injury in vivo and OGD-induced hippocampal neuronal apoptosis in vitro. Intrahippocampal silencing of XLOC_035088 significantly decreased brain XLOC_035088 expression, reduced brain infarct size, and improved neurological function through inhibiting NOTCH1 following derepression of presenilin 2 (PSEN2). Taken together, this study provides evidence that the lncRNA XLOC_035088/PSEN2/Notch1 axis is involved in the pathogenesis of ischemic brain injury, and presents a promising therapeutic route for ischemic stroke.

scholarly journals Long Course Hyperbaric Oxygen Stimulates Neurogenesis and Attenuates Inflammation after Ischemic Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-Sheng Lee ◽  
Chung-Ching Chio ◽  
Ching-Ping Chang ◽  
Liang-Chao Wang ◽  
Po-Min Chiang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hyperbaric Oxygen ◽  
Artery Occlusion ◽  
Trophic Factors ◽  
Therapeutic Effects ◽  
Ischemic Brain ◽  
Neurological Severity Score ◽  
Group Mobilization ◽  
Long Course ◽  
Cerebral Artery Occlusion

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

scholarly journals Hyperglycemia primes NETosis, which exacerbates ischemic brain damage

2019 ◽  
Author(s):  
Jiangshan Deng ◽  
Fei Zhao ◽  
Yunlong Zhang ◽  
Yajun Zhou ◽  
Xiaofeng Xu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Brain Damage ◽  
Artery Occlusion ◽  
Wild Type ◽  
Stroke Patients ◽  
Acute Hyperglycemia ◽  
Ischemic Brain ◽  
Infarction Volume ◽  
Cerebral Artery Occlusion

Abstract Background：Hyperglycemia is common and associated with poor outcomes in acute ischemic stroke patients. It is not well understood how hyperglycemia exacerbates brain damage in ischemic stroke. Neutrophil extracellular traps (NETs) have shown an emerging role in noninfectious diseases. We aimed to determine the role of NETs in acute ischemic stroke with hyperglycemia. Methods: NETs were immunostained using NET markers (citrullinated histone H3 (H3Cit)) and quantified in thrombi retrieved from ischemic stroke patients undergoing endovascular treatment. BKS-db/db and wild-type mice were used to establish the permanent middle cerebral artery occlusion (pMCAO) model. Wild-type mice were injected with glucose to simulate acute hyperglycemia after middle cerebral artery occlusion. NETs were detected in the peri-ischemic brain tissue. After inhibition of NET formation, infarction volume, neurological function and inflammatory factors in pMCAO mice were evaluated. Results: H3Cit, a marker of NETs, was observed in almost all thrombi. H3Cit was much more abundant in thrombi from diagnosed diabetic patients and acute hyperglycemic patients compared with those in normglycemic patients. In pMCAO mice, NETs were induced by chronic diabetes and acute hyperglycemia. Inhibition of NET formation with the peptidylarginine deiminase 4 (PAD4) inhibitor Cl-amidine decreased the infarction volume both in db/db and wild-type mice with hyperglycemia. Neurological function deficits were alleviated by blocking NET formation, as shown in the grip strength and rotarod tests. The levels of TNF-α and IL-1β but not IL-6 coincided with NET formation. Conclusions: Hyperglycemia may exacerbate brain damage in ischemic stroke through NETs. The underlying mechanisms deserve to be further studied.

scholarly journals Endothelial S1P 1 Signaling Counteracts Infarct Expansion in Ischemic Stroke

2020 ◽  
Author(s):  
Anja Nitzsche ◽  
Marine Poittevin ◽  
Ammar Benarab ◽  
Philippe Bonnin ◽  
Giuseppe Faraco ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Protective Role ◽  
Artery Occlusion ◽  
Spatial Modulation ◽  
Ischemic Brain ◽  
Cerebrovascular Function ◽  
Sphingosine 1 Phosphate ◽  
Infarct Expansion ◽  
Transient Models ◽  
Cerebral Artery Occlusion

Rationale: Cerebrovascular function is critical for brain health, and endogenous vascular-protective pathways may provide therapeutic targets for neurological disorders. Sphingosine 1-phosphate (S1P) signaling coordinates vascular functions in other organs, and S1P receptor-1 (S1P 1 ) modulators including fingolimod show promise for the treatment of ischemic and hemorrhagic stroke. However, S1P 1 also coordinates lymphocyte trafficking, and lymphocytes are currently viewed as the principal therapeutic target for S1P 1 modulation in stroke. Objective: To address roles and mechanisms of engagement of endothelial cell (EC) S1P 1 in the naïve and ischemic brain and its potential as a target for cerebrovascular therapy. Methods and Results: Using spatial modulation of S1P provision and signaling, we demonstrate a critical vascular protective role for endothelial S1P 1 in the mouse brain. With an S1P 1 signaling reporter, we reveal that abluminal polarization shields S1P 1 from circulating endogenous and synthetic ligands after maturation of the blood-neural barrier, restricting homeostatic signaling to a subset of arteriolar ECs. S1P 1 signaling sustains hallmark endothelial functions in the naïve brain, and expands during ischemia by engagement of cell-autonomous S1P provision. Disrupting this pathway by EC-selective deficiency in S1P production, export, or the S1P 1 receptor substantially exacerbates brain injury in permanent and transient models of ischemic stroke. By contrast, profound lymphopenia induced by loss of lymphocyte S1P 1 provides modest protection only in the context of reperfusion. In the ischemic brain, EC S1P 1 supports blood-brain barrier (BBB) function, microvascular patency, and the rerouting of blood to hypo-perfused brain tissue through collateral anastomoses. Selective S1P 1 agonism counteracts cortical infarct expansion after middle cerebral artery occlusion by engaging the endothelial receptor pool after BBB penetration. Conclusions: This study provides genetic evidence to support a pivotal role for the endothelium in maintaining perfusion and microvascular patency in the ischemic penumbra that is coordinated by S1P signaling and can be harnessed for neuroprotection with BBB-penetrating S1P 1 agonists.

scholarly journals Antineuroinflammatory effects of dl-3-n-butylphthalide conferred by stimulation of Foxp3 and Ki-67 in an ischemic stroke model

2020 ◽  
Author(s):  
Xi Liu ◽  
Runzhe Liu ◽  
Dongxu Fu ◽  
Hao Wu ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Artery Occlusion ◽  
Neurological Deficits ◽  
Stroke Model ◽  
Ki 67 ◽  
Ischemic Brain ◽  
Caspase 1 ◽  
And Function ◽  
Cerebral Artery Occlusion ◽  
First Time

Abstract Background Dl-3-n-butylphthalide (NBP) has been widely used for the treatment of ischemic stroke in China. However, its mechanisms of action have not been fully elucidated. Methods We established a permanent middle cerebral artery occlusion (pMCAO) rat model and administered 4 mg/kg/d NBP by tail vein injection for 9 days. Changes in some molecules related to neuroinflammation, neovascularization and nerve regeneration were observed, such as MALDI-TOF MSI to study the distribution of phospholipids in the brain, LA-ICP MSI to observe the changes of Foxp3, Ki-67 and pCREB, immunohistochemistry to investigate NLRP3 and its downstream inflammatory products Caspase-1 and IL-1β. Results These results showed that NBP attenuated ischemic damage in pMCAO rats, accompanied by improving neurological deficits. It was revealed for the first time in an animal stroke model that NBP decreased the levels of PE (18:0), NLRP3, Caspase-1 and IL-1β, while increasing the levels of several phospholipids, such as PA (16:0/18:1), PA (18:0/22:6), PE (16:0/22:6), PE (P-18:0/22:6), PE (18:0/22:6), PS (18:0/22:6), PI (18:0/20:4), Foxp3, Ki-67 and pCREB, in the ischemic brain region. Conclusion These results provide evidence that NBP can reduce neuroinflammation in brain tissue and promote the regeneration of nerves and blood vessels, thus exerting a protective effect on neuromorphology and function.

Expression of neurocan after transient middle cerebral artery occlusion in adult rat brain

2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S217-S217
Author(s):  
Kentaro Deguchi ◽  
Mikiro Takaishi ◽  
Takeshi Hayashi ◽  
Atsuhiko Oohira ◽  
Shoko Nagotani ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Rat Brain ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Adult Rat ◽  
Adult Rat Brain ◽  
Cerebral Artery Occlusion

Energy-Sensing Pathways in Ischemia: The Counterbalance Between AMPK and mTORC

2020 ◽  
Vol 25 (45) ◽  
pp. 4763-4770
Author(s):  
Angel Cespedes ◽  
Mario Villa ◽  
Irene Benito-Cuesta ◽  
Maria J. Perez-Alvarez ◽  
Lara Ordoñez ◽  
...  
Keyword(s):  
Blood Flow ◽  
Ischemic Stroke ◽  
Middle Cerebral Artery ◽  
Cause Of Death ◽  
Artery Occlusion ◽  
Brain Pathology ◽  
Common Cause ◽  
Specific Analysis ◽  
Energy Sensing ◽  
Cerebral Artery Occlusion

: Stroke is an important cause of death and disability, and it is the second leading cause of death worldwide. In humans, middle cerebral artery occlusion (MCAO) is the most common cause of ischemic stroke. The damage occurs due to the lack of nutrients and oxygen contributed by the blood flow. : The present review aims to analyze to what extent the lack of each of the elements of the system leads to damage and which mechanisms are unaffected by this deficiency. We believe that the specific analysis of the effect of lack of each component could lead to the emergence of new therapeutic targets for this important brain pathology.

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