Abstract W P86: Photo-stimulation of the Striatum Promotes Functional Recovery and Neurogenesis after Focal Ischemic Stroke

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mingke Song ◽  
Osama Mohamad ◽  
Xiaohuan Gu ◽  
Shipeng Wei ◽  
Ling Wei ◽  
...  

Introduction and Purpose: The striatum region of the brain supports self-repair process after experimental cerebral ischemia. Optogenetics is a temporally and spatially precise method to manipulate targeted neuronal populations. We tested whether optogenetic technique can be translated into stroke treatment by photo-stimulation of the striatum after focal cerebral ischemia. Methods: Adult male channelrhodopsin-2 (ChR2) transgenic mice were utilized, taking the advantage of that the cation channel ChR2 is abundantly expressed in the striatum. Before stroke, mice were trained 5 times per day for 3 days with a modified adhesive removal test. Mice were then subjected to the ischemic insult targeting the right sensorimotor (barrel) cortex. Four days after stroke, optical fibers were implanted into the striatum and fixed with a cannula on the skull. In control group, stoke mice received optical fiber implantation but without photo-stimulation. In treatment group, daily photo-stimulation pulses (473 nm blue laser) were started at 5 days after stroke and sustained for 8 days. The adhesive removal test on forepaws was performed 3, 10, 17, 24, and 31 days after stroke. Results: The impaired forepaw sensorimotor function in these two groups progressively recovered over the timeline. Stroke mice treated with photo-stimulation showed significantly better recovery assessed 31 days after stroke compared to stroke control. Our study also shows that the activity of neurogenesis in the brain was augmented by photo-stimulation, which may be responsible for enhanced functional recovery. Conclusions: Optogenetic stimulation of the striatum promotes functional recovery and neurogenesis after focal ischemic stroke.

2000 ◽  
Vol XXXII (3-4) ◽  
pp. 76-76
Author(s):  
J. Yrjanheikki ◽  
T. Tikka ◽  
R. Keinanen ◽  
G. Goldsteins ◽  
P. H. Chan ◽  
...  

One of the reasons for the insufficient effectiveness of treatment of acute ischemic stroke may be secondary inflammation of the brain tissue, which, according to the results of modern studies, significantly worsens the consequences and outcome of the disease.


2019 ◽  
Vol 85 (4) ◽  
pp. 18-26
Author(s):  
V.S. Lychko

The features of changes in the structural and functional characteristics of brain tissue were studied in 60 outbred male Wistar rats during modelling of acute focal cerebral ischemia (AFCI) in the dynamics of treatment with human cryopreserved cord blood serum (CCBS). Electronic and optical microscopic examination of the sensorimotor area of the cerebral cortex was performed. All animals were divided into three groups: the first (control) group consisted of intact rats without trauma and treatment; the second group consisted of animals after modelling AFCI without treatment; third group consisted of rats after modelling AFCI, which were injected by CCBS. Each group consisted of 20 animals. Material for morphological examination was taken after administration of CCBS solution to animals with the model of AFCI at 12, 24, 72 hours and 7th days after the start of the experiment. The average area of perivascular spaces, which is an indicator of vasogenic oedema in rats of group 2 was 45 times higher than in rats of group 1. In contrast, in rats of group 3 with CCBS, this figure was exceeded 37 times. The average area of pericellular spaces, indicating the degree of cytotoxic oedema, in animals of group 2 on the 7th day after AFCI was almost 23 times higher than the results of group 1. This figure in rats of group 3 was increased 20 times compared with data in group 2. Against the background of the use of this drug, there were signs of reactive changes in endothelial cells in the form of an increase in the number of ribosomes and polysomes in the cytoplasm, a decrease in the degree of perivascular oedema of brain tissue by 21.4 %. The surface area of endothelial cells in the zone of AFCI on the 7th day of the experiment in animals that additionally received CCBS was (1483.00±26.48) μm2, which indicates a positive anti-inflammatory effect of the drug. On the 7th day of the experiment in group 3 rats by optical microscopy was found to increase the density of cerebral capillaries compared with group 2, which indicates the stimulation of the restoration of the ultrastructure of damaged capillaries, increase their density, the formation of new capillaries under the components of CCBS.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuang-Lin Zhao ◽  
Gui Jin ◽  
Ze-Lin Bai ◽  
Jing-Bo Chen ◽  
Meng-Wei Li ◽  
...  

Abstract Background As a serious clinical disease, ischemic stroke is usually detected through magnetic resonance imaging and computed tomography. In this study, a noninvasive, non-contact, real-time continuous monitoring system was constructed on the basis of magnetic induction phase shift (MIPS) technology. The “thrombin induction method”, which conformed to the clinical pathological development process of ischemic stroke, was used to construct an acute focal cerebral ischemia model of rabbits. In the MIPS measurement, a “symmetric cancellation-type” magnetic induction sensor was used to improve the sensitivity and antijamming capability of phase detection. Methods A 24-h MIPS monitoring experiment was carried out on 15 rabbits (10 in the experimental group and five in the control group). Brain tissues were taken from seven rabbits for the 2% triphenyl tetrazolium chloride staining and verification of the animal model. Results The nonparametric independent-sample Wilcoxon rank sum test showed significant differences (p < 0.05) between the experimental group and the control group in MIPS. Results showed that the rabbit MIPS presented a declining trend at first and then an increasing trend in the experimental group, which may reflect the pathological development process of cerebral ischemic stroke. Moreover, TTC staining results showed that the focal cerebral infarction area increased with the development of time Conclusions Our experimental study indicated that the MIPS technology has a potential ability of differentiating the development process of cytotoxic edema from that of vasogenic edema, both of which are caused by cerebral ischemia.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 767
Author(s):  
Courtney Davis ◽  
Sean I. Savitz ◽  
Nikunj Satani

Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yan Feng ◽  
Hui Zhao ◽  
Fu-Dong Shi ◽  
Weina Jin

Objectives: To screen miRNA profile of peripheral NK cells in ischemic stroke mouse model and investigate a most promising candidate (miR-1224) for post-transcriptional regulation of NK cell function after ischemic stroke. Methods: Mice were subjected to a 60 min focal cerebral ischemia produced by transient intraluminal occlusion of MCAO. For NK cell isolation, cell suspensions from the spleens after reperfusion were enriched for NK cells using magnetic-bead sorting system after staining with anti-NK1.1 microbeads. The nCounter Mouse miRNA array was used to analyze miRNA expression profile in splenic NK cells over the time course of experimental ischemic stroke. Based on the miRNA data, we further in vitro modulated miR-1224 in NK cells using mimics or inhibitor, then injected i.v into Rag2-/-γc-/- recipient mice. Neurological function score was compared and spontaneous infection was assessed by pulmonary bacteria colony culture, and changes in potential signaling pathway (SP1/TNF-α) were verified by rt-PCR and western blot. Results: Through miRNA expression profile analysis, we have identified significant changes at each time point in peripheral NK cells after cerebral ischemia. Among all screened miRNA, miR-1224 remarkably increased in MCAO group, which was verified by PCR. Then isolated NK cells treated with mimics or inhibitors, were transferred to Rag2-/-γc-/- recipient mice. Compared with WT mice, Rag2-/-γc-/- mice with miR-1224 inhibitor exhibited increased NK cell number, enhanced NK cell activation/cytotoxicity feature, as well as better neurological behaviors and reduced pulmonary infection after MCAO. Moreover, compared with the control group, NK cells with miR-1224 inhibitor showed significantly increased SP1 gene and protein phosphorylation. As SP1 gene is one of the potential targets of miR-1224, this study suggests that miR-1224 may regulate NK cell function after MCAO, which is associated with SP1 pathway. Conclusion: The miRNA profiling of splenic NK cells provided insight into the functional mechanism and signaling pathways underlying the distinct organ-specific NK cell properties, which will contribute to the better understanding of NK cell mediated immune-response in relation to different stages of stroke.


Author(s):  
Dedy Budi Kurniawan ◽  
Mokhamad Fahmi Rizki Syaban ◽  
Arinal Mufidah ◽  
Muhammad Unzila Rafsi Zulfikri ◽  
Wibi Riawan

Stroke is one of the leading causes of morbidity and mortality in all ages. Ischemic stroke activates excitotoxic glutamate cascade leading to brain tissue injury. Saccharomyces cerevisiae is a unicellular yeast widely found in nature. S. cerevisiae is neuroprotective and able to increase the differentiation of hematopoietic stem cells (HSCs) into neuronal cells. it may increase levels of neuroprotectant BDNF in the brain tissue, therefore increase the protection of neurons. BDNF may prevent glutamate-driven excitotoxicity by reducing glutamate levels. This study uses a randomized post-test only controlled group design. In this in vivo study, rodent models of ischemic stroke were divided into five groups comprising of the negative control group, positive control group, intervention group 1 (18mg/kgBW), intervention group 2 (36mg/kgBW) and intervention group 3 (72 mg/kgBW). Groups treated with Saccharomyces cerevisiae extract showed significantly increased BDNF levels in the brain tissue, and the expression of the glutamate level was significantly reduced (P <0.05) compared to the positive control group. Thus Saccharomyces cerevisiae has a promising potential to become a therapy against ischemic stroke disease. however further research is needed regarding the efficacy and toxicity of Saccharomyces cerevisiae.


2017 ◽  
Vol 75 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Cristiane Iozzi Silva ◽  
Paulo Cézar Novais ◽  
Andressa Romualdo Rodrigues ◽  
Camila A.M. Carvalho ◽  
Benedicto Oscar Colli ◽  
...  

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.


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