Intermittent Skill Training Results in Moderate Improvement in Functional Outcome in a Mouse Model of Ischemic Stroke

2020 ◽  
Vol 35 (1) ◽  
pp. 79-87
Author(s):  
Victoria Nemchek ◽  
Emma M. Haan ◽  
Abigail L. Kerr

Background Stroke is a leading cause of disability worldwide. Focused training of the impaired limb has been shown to improve its functional outcome in animal models. However, most human stroke survivors exhibit persistent motor deficits, likely due to differences in rehabilitation intensity between experimental (animal) and clinical (human) settings. Objective The current study investigated the effect of training intensity on behavioral outcome in a mouse model of stroke. Methods Mice were trained preoperatively on a skilled reaching task. After training, mice received a unilateral photothrombotic stroke. Postoperatively, animals received either daily rehabilitative training (traditional intensity), intermittent rehabilitative training (every other day), or no rehabilitative training (control). Assessment of the impaired limb occurred after 14 training sessions (14 days for the Traditional group; 28 days for the Intermittent group). Results Assessment of the impaired limb illustrated that traditional, daily training resulted in significantly better performance than no training, while intermittent training offered moderate performance gains. Mice receiving intermittent training performed significantly better than control mice but did not exhibit reaching performance as strong as that of animals trained daily. Conclusions The intensity of rehabilitation is important for optimal recovery. Although intermediate intensity offers some benefit, it is not intensive enough to mimic the performance gains traditionally observed in animal models. These results suggest that intensive training, which is often unavailable for human stroke survivors, is necessary to achieve an optimal functional outcome. The lower bounds of training intensity for functional benefit still need to be determined.

Author(s):  
Alexander M. Kollikowski ◽  
Mirko Pham ◽  
Alexander G. März ◽  
Lena Papp ◽  
Bernhard Nieswandt ◽  
...  

AbstractExperimental evidence has emerged that local platelet activation contributes to inflammation and infarct formation in acute ischemic stroke (AIS) which awaits confirmation in human studies. We conducted a prospective observational study on 258 consecutive patients undergoing mechanical thrombectomy (MT) due to large-vessel-occlusion stroke of the anterior circulation (08/2018–05/2020). Intraprocedural microcatheter aspiration of 1 ml of local (occlusion condition) and systemic arterial blood samples (self-control) was performed according to a prespecified protocol. The samples were analyzed for differential leukocyte counts, platelet counts, and plasma levels of the platelet-derived neutrophil-activating chemokine C-X-C-motif ligand (CXCL) 4 (PF-4), the neutrophil attractant CXCL7 (NAP-2), and myeloperoxidase (MPO). The clinical-biological relevance of these variables was corroborated by specific associations with molecular-cellular, structural-radiological, hemodynamic, and clinical-functional parameters. Seventy consecutive patients fulfilling all predefined criteria entered analysis. Mean local CXCL4 (+ 39%: 571 vs 410 ng/ml, P = .0095) and CXCL7 (+ 9%: 693 vs 636 ng/ml, P = .013) concentrations were higher compared with self-controls. Local platelet counts were lower (− 10%: 347,582 vs 383,284/µl, P = .0052), whereas neutrophil counts were elevated (+ 10%: 6022 vs 5485/µl, P = 0.0027). Correlation analyses revealed associations between local platelet and neutrophil counts (r = 0.27, P = .034), and between CXCL7 and MPO (r = 0.24, P = .048). Local CXCL4 was associated with the angiographic degree of reperfusion following recanalization (r =  − 0.2523, P = .0479). Functional outcome at discharge correlated with local MPO concentrations (r = 0.3832, P = .0014) and platelet counts (r = 0.288, P = .0181). This study provides human evidence of cerebral platelet activation and platelet-neutrophil interactions during AIS and points to the relevance of per-ischemic thrombo-inflammatory mechanisms to impaired reperfusion and worse functional outcome following recanalization.


Medicine ◽  
2020 ◽  
Vol 99 (47) ◽  
pp. e23296
Author(s):  
Chong Pui Kei ◽  
Nor Azlin Mohd Nordin ◽  
Aznida Firzah Abdul Aziz

2019 ◽  
Vol 13 ◽  
Author(s):  
Nipaporn Butsing ◽  
Mathuros Tipayamongkholgul ◽  
Disya Ratanakorn ◽  
Nawarat Suwannapong ◽  
Kanitta Bundhamcharoen

AbstractSophisticated medical technologies can prolong a stroke patient’s life but not always their quality of life (QoL) due to poor functional outcomes. Social support can theoretically assist a patient’s adaptation to life after stroke and improve their QoL, but existing findings are inconclusive. This inconclusiveness is especially found in large cities where family and social bonding can be scarce. We conducted a hospital-based, cross-sectional study among 358 stroke patients to identify the effects of social support and functional outcome on QoL and its domains. The study took place in Bangkok, Thailand between July and December 2016. Data were collected by personal interview using a structured questionnaire that included the Short-Form WHO Quality of Life Instrument (WHOQOL-BREF) and by review of medical records. A hierarchical linear regression method was used to analyze data. The mean age of stroke respondents was 66.0 years (SD 13.5 years), and half were male. The mean total QoL score for patients was 68.6 (SD 15.2). Hierarchical multiple regression analysis found emotional support significantly impacted QoL in every domain (ps < .05) when all included variables were controlled for. To improve the quality of life among stroke survivors, health personnel and family members should provide not only physical assistance but also psychological support.


2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Lisa Miorin ◽  
Maudry Laurent-Rolle ◽  
Giuseppe Pisanelli ◽  
Pierre Hendrick Co ◽  
Randy A. Albrecht ◽  
...  

ABSTRACT The recent yellow fever virus (YFV) epidemic in Brazil in 2017 and Zika virus (ZIKV) epidemic in 2015 serve to remind us of the importance of flaviviruses as emerging human pathogens. With the current global flavivirus threat, there is an urgent need for antivirals and vaccines to curb the spread of these viruses. However, the lack of suitable animal models limits the research questions that can be answered. A common trait of all flaviviruses studied thus far is their ability to antagonize interferon (IFN) signaling so as to enhance viral replication and dissemination. Previously, we reported that YFV NS5 requires the presence of type I IFN (IFN-α/β) for its engagement with human signal transducer and activator of transcription 2 (hSTAT2). In this manuscript, we report that like the NS5 proteins of ZIKV and dengue virus (DENV), YFV NS5 protein is able to bind hSTAT2 but not murine STAT2 (mSTAT2). Contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, replacing mSTAT2 with hSTAT2 cannot rescue the YFV NS5-STAT2 interaction, as YFV NS5 is also unable to interact with hSTAT2 in murine cells. We show that the IFN-α/β-dependent ubiquitination of YFV NS5 that is required for STAT2 binding in human cells is absent in murine cells. In addition, we demonstrate that mSTAT2 restricts YFV replication in vivo. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses. IMPORTANCE Flaviviruses such as yellow fever virus (YFV), Zika virus (ZIKV), and dengue virus (DENV) are important human pathogens. A common flavivirus trait is the antagonism of interferon (IFN) signaling to enhance viral replication and spread. We report that like ZIKV NS5 and DENV NS5, YFV NS5 binds human STAT2 (hSTAT2) but not mouse STAT2 (mSTAT2), a type I IFN (IFN-α/β) pathway component. Additionally, we show that contrary to what has been demonstrated with ZIKV NS5 and DENV NS5, YFV NS5 is unable to interact with hSTAT2 in murine cells. We demonstrate that mSTAT2 restricts YFV replication in mice and that this correlates with a lack of IFN-α/β-induced YFV NS5 ubiquitination in murine cells. The lack of suitable animal models limits flavivirus pathogenesis, vaccine, and drug research. These data serve as further impetus for the development of an immunocompetent mouse model that can serve as a disease model for multiple flaviviruses.


2011 ◽  
Vol 2 (2) ◽  
pp. 138-143 ◽  
Author(s):  
Renée J. Turner ◽  
Glen C. Jickling ◽  
Frank R. Sharp
Keyword(s):  

Cephalalgia ◽  
2016 ◽  
Vol 36 (11) ◽  
pp. 1048-1056 ◽  
Author(s):  
Alycia F Tipton ◽  
Igal Tarash ◽  
Brenna McGuire ◽  
Andrew Charles ◽  
Amynah A Pradhan

Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine-preventive treatments. Methods Migraine therapies were administered to male and female mice for 11 days. On day 3, mice were tested with nitroglycerin every second day for nine days. Basal and nitroglycerin-evoked mechanical hypersensitivity was evaluated using von Frey filaments. Results Chronic intermittent nitroglycerin produced acute hyperalgesia with each administration, and progressive and sustained basal hypersensitivity. The established preventive migraine therapy propranolol effectively blocked the development of acute and chronic nitroglycerin-induced hyperalgesia, while valproate had no effect. Potential migraine-preventive therapies were also tested: Amiloride inhibited nitroglycerin-induced acute and chronic hyperalgesia; while memantine was ineffective. We also tested the acute migraine therapy sumatriptan, which did not alter nitroglycerin-induced hyperalgesia, but instead resulted in acute and chronic hyperalgesia similar to that observed following nitroglycerin administration. Conclusions This study establishes the chronic nitroglycerin model as an additional screening tool to test novel migraine-preventive therapies.


2003 ◽  
Vol 16 (1) ◽  
pp. 16-25 ◽  
Author(s):  
Frances P. Noonan ◽  
James Dudek ◽  
Glenn Merlino ◽  
Edward C. De Fabo

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