Overexpression of ORX or MCH Protects Neurological Function Against Ischemic Stroke

2022 ◽  
Author(s):  
Gang Wu ◽  
Xi’an Zhang ◽  
Shijun Li ◽  
Dan Zhou ◽  
Jie Bai ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neurological Function

scholarly journals Intranasal Salvinorin A Improves Long-term Neurological Function via Immunomodulation in a Mouse Ischemic Stroke Model

2021 ◽  
Author(s):  
Dilidaer Misilimu ◽  
Wei Li ◽  
Di Chen ◽  
Pengju Wei ◽  
Yichen Huang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Blood Brain Barrier ◽  
Immune Cells ◽  
Intranasal Administration ◽  
Neurological Function ◽  
Salvinorin A ◽  
Stroke Model ◽  
Peripheral Immune Cells ◽  
The Brain

AbstractSalvinorin A (SA), a highly selective kappa opioid receptor agonist, has been shown to reduce brain infarct volume and improve neurological function after ischemic stroke. However, the underlying mechanisms have not been fully understood yet. Therefore, we explored whether SA provides neuroprotective effects by regulating the immune response after ischemic stroke both in the central nervous system (CNS) and peripheral circulation. In this study, adult male mice were subjected to transient Middle Cerebral Artery Occlusion (tMCAO) and then were treated intranasally with SA (50 μg/kg) or with the vehicle dimethyl sulfoxide (DMSO). Multiple behavioral tests were used to evaluate neurofunction. Flow cytometry and immunofluorescence staining were used to evaluate the infiltration of peripheral immune cells into the brain. The tracer cadaverine and endogenous immunoglobulin G (IgG) extravasation were used to detect blood brain barrier leakage. We observed that SA intranasal administration after ischemic stroke decreased the expression of pro-inflammatory factors in the brain. SA promoted the polarization of microglia/macrophages into a transitional phenotype and decreased the pro-inflammatory phenotype in the brain after tMCAO. Interestingly, SA treatment scarcely altered the number of peripheral immune cells but decreased the macrophage and neutrophil infiltration into the brain at 24 h after tMCAO. Furthermore, SA treatment also preserved BBB integrity, reduced long-term brain atrophy and white matter injury, as well as improved the long-term neurofunctional outcome in mice. In this study, intranasal administration of SA improved long-term neurological function via immuno-modulation and by preserving blood–brain barrier integrity in a mouse ischemic stroke model, suggesting that SA could potentially serve as an alternative treatment strategy for ischemic stroke. Graphic Abstract

Therapeutic effects of different treatment periods against ischemic stroke and toxicology study of Angong Niuhuang Pill in rats

2020 ◽  
Author(s):  
Jianzhao Chen ◽  
Yushuang Chai ◽  
Yuanfeng He ◽  
Jisheng Huang ◽  
Ting Wan ◽  
...  
Keyword(s):  
Body Weight ◽  
Ischemic Stroke ◽  
Protective Effect ◽  
Toxic Effect ◽  
Treatment Period ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
The Body ◽  
Therapeutic Effects ◽  
Toxicology Study

Abstract Background : Angong Niuhuang Pill (ANP) is one of the most famous drugs to treat stroke in China, but there is no definite treatment period in drug instruction. In this study, we used middle cerebral artery occlusion (MCAO) model to evaluate its therapeutic effects of different treatment periods and studied its toxic effect in rats. Methods : Protective effect of ANP was observed in the cerebral ischemia-reperfusion model in rats; ANP (270 mg/kg) three different treatment period included 1 day, 4 days and 7 days. The observation period was 30 days. Therapeutic effect was evaluated by detecting neurological function, cerebral infraction volume, brain histology and cytokines. Three dose including 550, 1640, 4910 mg/kg were studied in toxicology study. The administration period was 30 days. Toxic effect was evaluated by detecting appearance, behavior, excrement character, food-intake, body weight, hematological parameters and biomarkers such as TBA, GSTα, Cystatin C, clusterin, GSH, S-100B and MBP. Results : Seven days treatment period of ANP had better effect than 1 day and 4 days treatment periods in rat MCAO model from neurological function scores, the volume of cerebral infarction, brain histology and the serum content of IL-1β, TNF-α and NO; the brain content of IL-1β and NO. The results of 30 days multiple dose toxicology study showed no animal death in all groups; in ANP 4910 mg/kg group, the kidney and liver coefficient increased about 10%, the body weight grew more slowly, the TBA increased slightly. There was no abnormal change in histology. These all recovered after drug withdraw for 8 weeks. Conclusion: Seven days treatment period of ANP had more protective effect than 1 day and 4 days treatment periods in ischemic stroke rat. No observed adverse effect level (NOAEL) of ANP was 1640 mg/kg; the safety margin of ANP was 270-1640 mg/kg. These data provided reference to modify drug instruction.

scholarly journals Dodecafluoropentane Improves Neurological Function Following Anterior Ischemic Stroke

2016 ◽  
Vol 54 (6) ◽  
pp. 4764-4770 ◽  
Author(s):  
M. Christine Arthur ◽  
Aliza Brown ◽  
Kristen Carlson ◽  
John Lowery ◽  
Robert D. Skinner ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neurological Function

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.

scholarly journals Silencing lncRNA HOTAIR improves the recovery of neurological function in ischemic stroke via the miR-148a-3p/KLF6 axis

2021 ◽  
Author(s):  
Yiwen Huang ◽  
Yuanyuan Wang ◽  
Xiaobin Liu ◽  
Yingjun Ouyang
Keyword(s):  
Ischemic Stroke ◽  
Neurological Function ◽  
Neurological Injury ◽  
Spatial Learning And Memory ◽  
Stat3 Pathway ◽  
N2a Cells ◽  
Apoptosis And Inflammation ◽  
Lncrna Hotair

Abstract Ischemic stroke (IS), caused by a permanent or transient local reduction in blood supply to the brain, is one of the most widespread causes of public health problems in modern society. Long non-coding RNA (LncRNA) has been reported to be related to angiogenesis following IS. In this study, we explored the effect and potential molecular mechanism of lncRNA HOTAIR in IS. Permanent middle cerebral artery occlusion (pMCAO) model and oxygen and glucose deprivation (OGD) model were established. HOTAIR was increased in vivo and in vitro models post-ischemic. HOTAIR knockdown promoted neurological function recovery, manifesting in decreased modified neurological severity score, cerebral infarcted area, apoptosis and inflammation, and improved balance ability, spatial learning and memory ability. Silencing HOTAIR also improved the viability of OGD-induced N2a cells, and attenuated apoptosis and inflammation. HOTAIR can compete with KLF6 to bind to miR-148a-3p. miR-148a-3p knockdown or KLF6 overexpression partially reversed the effect of sh-HOTAIR on OGD-induced N2a cells. HOTAIR suppressed the activation of STAT3 pathway via the miR-148a-3p/KLF6 axis. To summarize, this study demonstrated that lncRNA HOTAIR absorbed miR-148a-3p and up-regulate KLF6 expression through ceRNA mechanism, and inhibited STAT3 pathway, promoted apoptosis and inflammation, and aggravated neurological injury post-IS.

scholarly journals Curative Effect of Interventional Therapy and Neurological Changes in Ischemic Stroke of Posterior Circulation Evaluated by Magnetic Resonance Imaging under Genetic Algorithm

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Xiaodu Yu ◽  
Xingyou Zheng ◽  
Daoyou Cheng
Keyword(s):  
Magnetic Resonance Imaging ◽  
Genetic Algorithm ◽  
Ischemic Stroke ◽  
Magnetic Resonance ◽  
Compressed Sensing ◽  
Interventional Therapy ◽  
Neurological Function ◽  
Posterior Circulation ◽  
Resonance Imaging ◽  
Before And After

Objective. This study aimed to evaluate the improvement and neurological function changes of patients with ischemic stroke in the posterior circulation before and after interventional therapy using magnetic resonance imaging (MRI) under genetic algorithm and compressed sensing algorithm. Methods. Thirty-six patients with posterior circulation ischemia who visited the interventional cerebrovascular disease area were included in this study. The treatment effect was observed through abnormal signal changes in the lesion area on each sequence of MRI images before and after treatment. The National Institutes of Health Stroke Scale (NIHSS) was used for the evaluation of the changes in neurological function. Results. The real data experiment results suggested that the peak signal-to-noise ratio (PSNR) = 39.33 and structure similarity (SSIM) = 0.96 in the algorithm reconstructed image, which showed no significant difference with the simulation experiment results of PSNR = 35.19 and SSIM = 0.96 ( P < 0.05 ). In addition, the stenosis rate after interventional treatment (13.89%) was substantially lower than that before treatment (91.67%) ( P < 0.05 ). Cerebral blood flow (CBF) of the bilateral occipital lobes and cerebellum after six months of treatment was higher than that before treatment ( P < 0.05 ), and the incidence of postoperative restenosis was 11.11% (4/36). Conclusion. The combination of genetic algorithm and compressed sensing algorithm had a good effect on MRI image processing. The posterior circulation ischemia interventional stent implantation can effectively improve the stenosis of the vertebral artery and vertebral basilar artery as well as the cerebral tissue perfusion in the ischemic area, which improved the clinical symptoms substantially and reduced the probability of restenosis.

scholarly journals Association between serum lipoprotein levels and neurological function in patients with acute ischemic stroke

Medicine ◽  
2020 ◽  
Vol 99 (20) ◽  
pp. e20258
Author(s):  
Yao-Jia Jiang ◽  
Zeng-Mian Wang ◽  
Ze-Yu Wang ◽  
Chun-Jie Wei
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Serum Lipoprotein ◽  
Neurological Function
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