Abstract 97: Intra-Arterial Cell Transplantation Provides Timing-Dependent Cell Distribution and Functional Recovery After Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Shunsuke Ishizaka ◽  
Nobutaka Horie ◽  
Yutaka Fukuda ◽  
Katsuya Satoh ◽  
Noriyuki Nishida ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Functional Recovery ◽  
Human Mesenchymal Stem Cells ◽  
Serum Levels ◽  
Artery Occlusion ◽  
Control Group ◽  
Cell Distribution ◽  
Post Stroke ◽  
Dependent Cell ◽  
Cerebral Artery Occlusion

Background and Purpose— Intra-arterial cell transplantation offers a novel therapeutic strategy for stroke; however, it remains unclear how the timing of cell administration affects cell distribution, brain repair processes and functional recovery. Here, we investigate the hypothesis that the timing of cell transplantation changes the behavior of the cell graft and the host environment in a way that affects functional recovery. Methods— Rats received human mesenchymal stem cells (hMSCs) via the internal carotid artery at 1, 4 or 7 days (D1, D4 or D7) after middle cerebral artery occlusion and reperfusion. Animals were sacrificed at various time points to assess cell distribution in correlation with the host cerebral hemodynamics, serum levels of matrix metallopeptidase-9 (MMP-9), infiltration of activated microglia, expression of brain derived neurotrophic factor (BDNF), angiogenesis, presence of reactive astrocytes, and neurological recovery. Results— hMSCs were widely distributed both in the periinfarct and core in D1, and dominantly in the periinfarct in D4, in parallel with the cerebral hemodynamic change. Very few cells were observed in D7. Only in D1 group, the serum level of MMP-9 is significantly lower than that in control group at 72 hours after cell transplantation. At day 7 post-stroke, activation of microglia was significantly suppressed both in the periinfarct and core in D1, and only in the periinfarct in D4. At day 21 post-stroke, BDNF was widely distributed throughout the periinfarct in D1 and D4, and angiogenesis was enhanced. Motor function improved earlier in D1 and later in D4, but only D1 exhibited reduced atrophy. Conclusions— Our results indicate that intra-arterial cell transplantation provides timing-dependent cell distribution and post-stroke functional recovery via a combination of two mechanisms: neuroprotection and neurorestoration.

scholarly journals Therapeutic Benefits by Human Mesenchymal Stem Cells (hMSCs) and Ang-1 Gene-Modified hMSCs after Cerebral Ischemia

2007 ◽  
Vol 28 (2) ◽  
pp. 329-340 ◽  
Author(s):  
Toshiyuki Onda ◽  
Osamu Honmou ◽  
Kuniaki Harada ◽  
Kiyohiro Houkin ◽  
Hirofumi Hamada ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Artery ◽  
Human Mesenchymal Stem Cells ◽  
Artery Occlusion ◽  
Control Group ◽  
Therapeutic Effects ◽  
Lesion Volume ◽  
Therapeutic Benefits ◽  
Cerebral Artery Occlusion

Transplantation of human mesenchymal stem cells (hMSCs) prepared from adult bone marrow has been reported to ameliorate functional deficits after cerebral artery occlusion in rats. Although several hypotheses to account for these therapeutic effects have been suggested, current thinking is that both neuroprotection and angiogenesis are primarily responsible. In this study, we compared the effects of hMSCs and angiopoietin-1 gene-modified hMSCs (Ang-hMSCs) intravenously infused into rats 6 h after permanent middle cerebral artery occlusion. Magnetic resonance imaging and histologic analyses revealed that rats receiving hMSCs or Ang-hMSCs exhibited comparable reduction in gross lesion volume as compared with the control group. Although both cell types indeed improved angiogenesis near the border of the ischemic lesions, neovascularization and regional cerebral blood flow were greater in some border areas in Ang-hMSC group. Both hMSC- and Ang-hMSC-treated rats showed greater improved functional recovery in the treadmill stress test than did control rats, but the Ang-hMSC group was greater. These results indicate the intravenous administration of genetically modified hMSCs to express angiopoietin has a similar effect on reducing lesion volume as hMSCs, but the Ang-hMSC group showed enhanced regions of increased angiogenesis at the lesion border, and modest additional improvement in functional outcome.

scholarly journals Intra-arterial Cell Transplantation Provides Timing-Dependent Cell Distribution and Functional Recovery After Stroke

Stroke ◽  
2013 ◽  
Vol 44 (3) ◽  
pp. 720-726 ◽  
Author(s):  
Shunsuke Ishizaka ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Yuhtaka Fukuda ◽  
Noriyuki Nishida ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Functional Recovery ◽  
Cell Distribution ◽  
Dependent Cell

Early Functional Recovery and the Fate of the Diffusion/Perfusion Mismatch in Patients with Proximal Middle Cerebral Artery Occlusion

2003 ◽  
Vol 17 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Oliver C. Singer ◽  
Richard du Mesnil de Rochemont ◽  
Christian Foerch ◽  
Astrid Stengel ◽  
Matthias Sitzer ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Functional Recovery ◽  
Artery Occlusion ◽  
Proximal Middle Cerebral Artery ◽  
Cerebral Artery Occlusion ◽  
Early Functional Recovery

Abstract WP118: The Flavanol (-)-Epicatechin Improves Functional Recovery In Mice Subjected To Experimental Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Christopher C Leonardo ◽  
Sean Robbins ◽  
Abdullah A Ahmad ◽  
Sylvain Dore
Keyword(s):  
Functional Recovery ◽  
Transcriptional Activation ◽  
Infarct Volume ◽  
Epidemiological Studies ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Adhesive Tape ◽  
Dietary Consumption ◽  
Therapeutic Doses ◽  
Cerebral Artery Occlusion

Background: Epidemiological studies indicate that flavanol consumption reduces the propensity to develop cerebrovascular disease. Available data suggest actions on multiple pro-inflammatory pathways, yet it remains unclear which pathways mediate functional recovery after stroke. Our goal is to begin identifying the mechanisms by which the flavanol (-)-epicatechin (EC) improves anatomical and functional outcomes. Based upon data from initial dose-response experiments, ongoing studies are investigating hypothesized protective pathways involving matrix metalloproteinase-mediated blood brain barrier protection and Nrf2 transcriptional activation. Methods: Male, 8-10wk old C57BL/6 mice were pretreated with EC 90m prior to permanent distal middle cerebral artery occlusion. Vehicle or EC was administered by oral gavage to mimic dietary consumption. Mice were evaluated 1, 4 and 7d post-stroke for performance on various sensorimotor tasks prior to histological assessments. Results: Initial experiments demonstrated that mice treated with 15mg/kg EC showed reduced latency to remove adhesive tape at 1d compared to vehicle controls (n=12, p<0.01). Similarly, immunoreactivity for the microglia/macrophage marker Iba1 was increased in the ipsilateral hemispheres of mice 7d after treatment with vehicle (p<0.01), whereas pretreatment with 15mg/kg blocked this effect (n=4). Mice treated with 15mg/kg also showed a trend toward reduced infarct volume relative to vehicle controls (n=5-9 per group). In subsequent reduced dosing studies, vehicle-treated mice again showed deficiencies in removing adhesive tape at 1d (n=8, p<0.01). Remarkably, mice treated with 15, 10 or 5mg/kg EC showed no deficits. Similarly, vehicle control mice showed grip strength impairments up to 7d (n=8, p<0.05) that were absent in all groups of EC-treated mice. Conclusions: Preventative administration of EC promotes functional recovery in mice subjected to experimental stroke. Investigations are underway to determine the pathways mediated by EC following administration at these therapeutic doses. Together, these data will provide insights into the potential for (-)-epicatechin as a clinical therapeutic.

Abstract TP93: Topically Applied Adipose-derived Mesenchymal Stem Cell Treatment In Experimental Focal Cerebral Ischemia

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
George Wong ◽  
Keyword(s):  
Stem Cell ◽  
Cerebral Ischemia ◽  
Mesenchymal Stem Cell ◽  
Parietal Cortex ◽  
Cerebral Artery ◽  
Topical Application ◽  
Artery Occlusion ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Cerebral Artery Occlusion

Background and purpose: Disability is common after severe stroke resulting from major cerebral artery occlusion despite adoption of prophylactic decompressive craniectomy. Experimental mesenchymal stem cell treatments are commonly administrated through systemic infusion, with limitations in dosage. In this study, the neuro-modulation effect of topical mesenchymal stem cells (MSCs) was tested in a rodent middle carotid artery occlusion (MCAO) model. Methods: Twenty-four hours after MCAO, craniotomy was made and 0.8 x 10 6 GFP-MSCs were topically applied to the ipsilateral parietal cortex (N=30). In the control group, saline were topically applied to the ipsilateral parietal cortex (N=30). Results: After topical MSC treatment, neurological assessments with Rotarod test (at days 3, 7, and 10) and Morris Water Maze test (at days 3, 7, and 14) were significantly better, as compared to the control group; the infarct volume was also smaller. MSCs were found in the penumbra of the infarct 3 days after topical application. In the PCR array analysis of the RNA extracted from penumbra cortex, topical application of MSCs changed 10 gene expressions in the penumbra at day 3 (fold change >1.25, p<0.05 after Bonferroni corrections for multiple comparisons). The seven up-regulated genes (Apoe, Ascl1, Efnb1, Mef2c,Nog,S100a6, B2m) involve neuronal migration, neuronal differentiation, neuronal cell fate determination, regulation of synaptic plasticity, axonogensis;, growth factors, and cell adhesion. Pax2, Pax3 and Th were downregulated. Pax2 and Pax3 are related to apoptosis. Both Apoe and Thl involve synaptic transmission. Conclusions: Topically applied MSCs reduced cerebral infarction volume and improved the neurological function from cerebral ischemia resulting from a major cerebral artery occlusion in a rodent experimental model.

scholarly journals Impact of Key Nicotinic AChR Subunits on Post-Stroke Pneumococcal Pneumonia

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 253
Author(s):  
Sandra Jagdmann ◽  
Claudia Dames ◽  
Daniel Berchtold ◽  
Katarzyna Winek ◽  
Luis Weitbrecht ◽  
...  
Keyword(s):  
Artery Occlusion ◽  
Experimental Stroke ◽  
Medical Complication ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Post Stroke ◽  
Cholinergic Signaling ◽  
Cerebral Artery Occlusion ◽  
Pathogen Clearance ◽  
The Impact ◽  
Alveolar Capillary

Pneumonia is the most frequent severe medical complication after stroke. An overactivation of the cholinergic signaling after stroke contributes to immunosuppression and the development of spontaneous pneumonia caused by Gram-negative pathogens. The α7 nicotinic acetylcholine receptor (α7nAChR) has already been identified as an important mediator of the anti-inflammatory pathway after stroke. However, whether the α2, α5 and α9/10 nAChR expressed in the lung also play a role in suppression of pulmonary innate immunity after stroke is unknown. In the present study, we investigate the impact of various nAChRs on aspiration-induced pneumonia after stroke. Therefore, α2, α5, α7 and α9/10 nAChR knockout (KO) mice and wild type (WT) littermates were infected with Streptococcus pneumoniae (S. pneumoniae) three days after middle cerebral artery occlusion (MCAo). One day after infection pathogen clearance, cellularity in lung and spleen, cytokine secretion in bronchoalveolar lavage (BAL) and alveolar-capillary barrier were investigated. Here, we found that deficiency of various nAChRs does not contribute to an enhanced clearance of a Gram-positive pathogen causing post-stroke pneumonia in mice. In conclusion, these findings suggest that a single nAChR is not sufficient to mediate the impaired pulmonary defense against S. pneumoniae after experimental stroke.

scholarly journals Effects of Shaoyao-Gancao Decoction on Infarcted Cerebral Cortical Neurons: Suppression of the Inflammatory Response following Cerebral Ischemia-Reperfusion in a Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Ying Zhang ◽  
Xinling Jia ◽  
Jian Yang ◽  
Qing Li ◽  
Guofeng Yan ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Brain Tissue ◽  
Cortical Neurons ◽  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Artery Occlusion ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Cortical Neurons ◽  
Staining Methods ◽  
Cerebral Artery Occlusion

The mechanisms by which Shaoyao-Gancao decoction (SGD) inhibits the production of inflammatory cytokines in serum and brain tissue after cerebral ischemia-reperfusion (CI-RP) in rats were investigated. A right middle cerebral artery occlusion was used to induce CI-RP after which the rats were divided into model (n=39), SGD (n=28), clopidogrel (n=25) and sham operated (n=34) groups. The Bederson scale was used to evaluate changes in behavioral indices. The levels of IL-1β, TNF-α, MCP-1, IL-10, RANTES, VEGF, and TGF-β1 in the serum and infarcted brain tissues were measured. Nissl body and immunohistochemical staining methods were used to detect biochemical changes in neurons, microglial cells, and astrocytes. Serum levels of VEGF, TNF-α, MCP-1, IL-1β, and IL-10 increased significantly 24 h after CI-RP. In brain tissue, levels of TNF-αand IL-1βsignificantly increased 24 h after CI-RP, whereas levels of TGF-β1 and MCP-1 were significantly higher 96 h after CI-RP (P<0.05). SGD or clopidogrel after CI-RP reduced TNF-αand IL-1βlevels in brain tissue and serum levels of MCP-1, IL-1β, and IL-10. SGD increased the number of NeuN-positive cells in infarcted brain tissue and reduced the number of IBA1-positive and GFAP-positive cells. The efficacy of SGD was significantly higher than that of clopidogrel.

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