[P4–104]: ATTENUATION OF AKT‐MTORC1‐P70S6K ACTIVATION, TAU PHOSPHORYLATION AND INFLAMMATION IN THE CEREBRAL CORTEX INFARCTED BY PHOTOCHEMICALLY INDUCED THROMBOSIS BY REHABILITATION TRAINING
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Although stroke elicits progressive cognitive decline and is a major cause of dementia, molecular interplay between stroke and Alzheimer's disease (AD) pathology has not been fully elucidated. Furthermore, studies on the effects of post-stroke rehabilitation on AD pathology are limited. The care of animals and a protocol approved by the Institutional Animal Care and Handling Committee. Sprague-Dawley rats were randomly assigned to rehabilitation group (RG) and sedentary control group (SC) following photothrombotic infarction in the dominant side of sensorimotor cortex. RG received 4-weeks of task-specific rehabilitation once daily by single pellet reaching training (SPRT). Cortical expression levels of proteins related to tau modification and inflammation were evaluated on post-stroke day (PSD) 1 and 28. The expression levels of acetyl-tau, phosphorylated-tau at Ser262(p-tauS262) and Ser202/Thr205 (p-tau202/205) and truncated tau on PSD1 were significantly higher in infarcted cortex (ipsilateral) than the paired non-ischemic cortex (contralateral), whereas p-tauS396 levels was comparable. The positive feedback loop of Akt-mTORC2 (p-Sin1) and concurrent activation of mTORC1-p70S6K pathway in ipsilateral sides on PSD1 were significantly greater, whereas the expression levels of p-AMPK, GSK3β activity, Sirt1 and brain-derived neurotrophic factor were significantly lower than in the paired contralateral sides. The acute increase of cyclooxygenase 2 (COX-2) levels was also observed. The rehabilitation by SPRT for 4 weeks significantly attenuated the tau phosphorylation and activation of Akt-mTORC1-p70S6K pathway in ipsilateral cortex of RG, as compared to those in ipsilateral cortex of SC, which concurred with improvement of functional motor performance but not memory. In addition, the levels of ipsilateral p-AMPK and COX-2 of RG was significantly lower than those of SC, whereas the ipsilateral GSK3β activity and acetyl tau levels of RG were comparable to those of SC. Photothrombotic cortical infarction was found to induce cortical tau modification through the Akt-mTORC1-p70S6K activation, and to downregulate the expression of AMPK-related proteins. Task-specific rehabilitation for 4 weeks greatly improved motor function, but not memory, and suppressed p-tau expression and neuroinflammation. These results indicated that rehabilitation training may attenuate the acute pathologic changes related to tau modification and inflammation after cortical ischemic damage.Keywords:
Stroke
Abstract Inflammationis the body’s response to cellular injury. It serves to dilute and remove injurious agents and trigger healing of the damaged tissue. Although inflammation is intended to be a protective response, it may also be harmful when inappropriately activated. Inflammation is elicited by any form of cellular damage including infection, physical injury, chemical injury, and ischaemia. Be careful not to equate inflammation with infection. Whilst infection is often accompanied by inflammation, there are many diseases characterized by inflammation which are not caused by infection, such as autoimmune diseases, and even some infectious diseases where inflammation is absent, e.g. variant Creutzfeldt–Jacob disease.
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The article discusses the history of brain neuroplasticity, its effect on the restoration of functions after a stroke. Various mechanisms of neuroplasticity are considered: functions of reorganization, neurogenesis, the effect on neuroplasticity of training, the use of various rehabilitation techniques, and drug therapy.
Stroke
Stroke Recovery
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This chapter contains sections titled: Clinical characteristics of inflammation Phases of inflammation Innate defence mechanisms Cell apoptosis and inflammation Major histocompatibility complex and inflammation Cellular components of cutaneous inflammation Mediators of inflammation Vasculature and inflammation References
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Transcranial Direct Current Stimulation
Premovement neuronal activity
Brain stimulation
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Phantom limb
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The article discusses the history of brain neuroplasticity, its effect on the restoration of functions after a stroke. Various mechanisms of neuroplasticity are considered: functions of reorganization, neurogenesis, the effect on neuroplasticity of training, the use of various rehabilitation techniques, and drug therapy.
Stroke
Stroke Recovery
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Background Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown. Objective The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition. Methods We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS) paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS. Results Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons). The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise. Conclusions Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response.
Aerobic Exercise
Stroke
Brain stimulation
Functional electrical stimulation
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Irregular inflammatory responses are a major contributor to tissue dysfunction and inefficient repair. Skin has proven to be a powerful model to study mechanisms that regulate inflammation. In particular, skin wound healing is dependent on a rapid, robust immune response and subsequent dampening of inflammatory signaling. While injury-induced inflammation has historically been attributed to keratinocytes and immune cells, a vast body of evidence supports the ability of non-immune cells to coordinate inflammation in numerous tissues and diseases. In this review, we concentrate on the active participation of tissue-resident adipocytes and fibroblasts in pro-inflammatory signaling after injury, and how altered cellular communication from these cells can contribute to irregular inflammation associated with aberrant wound healing. Furthering our understanding of how tissue-resident mesenchymal cells contribute to inflammation will likely reveal new targets that can be manipulated to regulate inflammation and repair.
Skin repair
Tissue Repair
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