Robot‐assisted mechanical therapy attenuates stroke‐induced limb skeletal muscle injury

Sen, Chandan K.; Khanna, Savita; Harris, Hallie; Stewart, Richard; Balch, Maria; Heigel, Mallory; Teplitsky, Seth; Gnyawali, Surya; Rink, Cameron

doi:10.1096/fj.201600437r

Cited by 17 publications

(17 citation statements)

References 49 publications

(58 reference statements)

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“…Exact molecular mechanisms of AIS-induced muscular decline are unclear. Myostatin is upregulated in post-stroke paretic muscle [ 13 , 108 ]. Myostatin inhibits the anabolic Akt/mammalian target of rapamycin (mTOR) pathway while increasing ubiquitin-proteasome activity and autophagy-lysosome proteolysis [ 108 ].…”

Section: Motor Pathway Disruptionmentioning

confidence: 99%

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

et al. 2020

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Stroke research has traditionally focused on the cerebral processes following ischemic brain injury, where oxygen and glucose deprivation incite prolonged activation of excitatory neurotransmitter receptors, intracellular calcium accumulation, inflammation, reactive oxygen species proliferation, and ultimately neuronal death. A recent growing body of evidence, however, points to far-reaching pathophysiological consequences of acute ischemic stroke. Shortly after stroke onset, peripheral immunodepression in conjunction with hyperstimulation of autonomic and neuroendocrine pathways and motor pathway impairment result in dysfunction of the respiratory, urinary, cardiovascular, gastrointestinal, musculoskeletal, and endocrine systems. These end organ abnormalities play a major role in the morbidity and mortality of acute ischemic stroke. Using a pathophysiology-based approach, this current review discusses the pathophysiological mechanisms following ischemic brain insult that result in end organ dysfunction. By characterizing stroke as a systemic disease, future research must consider bidirectional interactions between the brain and peripheral organs to inform treatment paradigms and develop effective, comprehensive therapeutics for acute ischemic stroke.

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Section: Motor Pathway Disruptionmentioning

confidence: 99%

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

et al. 2020

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“…Signal was visualized by subsequent incubation with fluorescencetagged secondary Ab (Alexa Fluor 568-tagged a-rabbit, 1:200) and counterstained with DAPI (Thermo Fisher Scientific). Images were captured on an Axio Observer.Z1 (Ziess), and mean fluorescent intensity from images was quantified by using Zen 2 (blue edition) software (Ziess) (31)(32)(33).…”

Section: Immunohistochemistry and Microscopymentioning

confidence: 99%

Phytoestrogen isoflavone intervention to engage the neuroprotective effect of glutamate oxaloacetate transaminase against stroke

et al. 2017

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In the pathophysiologic setting of cerebral ischemia, excitotoxic levels of glutamate contribute to neuronal cell death. Our previous work demonstrated the ability of glutamate oxaloacetate transaminase (GOT) to metabolize neurotoxic glutamate in the stroke-affected brain. Here, we seek to identify small-molecule inducers of GOT expression to mitigate ischemic stroke injury. From a panel of phytoestrogen isoflavones, biochanin A (BCA) was identified as the most potent inducer of GOT gene expression in neural cells. BCA significantly increased GOT mRNA and protein expression at 24 h and protected against glutamate-induced cell death. Of note, this protection was lost when GOT was knocked down. To validate outcomes , C57BL/6 mice were intraperitoneally injected with BCA (5 and 10 mg/kg) for 4 wk and subjected to ischemic stroke. BCA levels were significantly increased in plasma and brain of mice. Immunohistochemistry demonstrated increased GOT protein expression in the brain. BCA attenuated stroke lesion volume as measured by 9.4T MRI and improved sensorimotor function-this protection was lost with GOT knockdown. BCA increased luciferase activity in cells that were transfected with the pERREtk-LUC plasmid, which demonstrated transactivation of GOT. This increase was lost when estrogen-related receptor response element sites were mutated. Taken together, BCA represents a natural phytoestrogen that mitigates stroke-induced injury by inducing GOT expression.-Khanna, S., Stewart, R., Gnyawali, S., Harris, H., Balch, M., Spieldenner, J., Sen, C. K., Rink, C. Phytoestrogen isoflavone intervention to engage the neuroprotective effect of glutamate oxaloacetate transaminase against stroke.

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“…Capogrosso et al used a kinematic analysis system to analyze walking disorders and balance de cits that occurred after spinal cord injury in rhesus monkeys (10). Nevertheless, although various assessment devices and gait parameters have been reported for the evaluation of gait function (11)(12)(13)(14), temporo-spatial and kinetic walking characteristics of rhesus monkeys have not been investigated. In the present study, we described the walking gait of healthy rhesus monkeys and developed a normal gait database using a pressure distribution sensor apparatus.…”

Section: Introductionmentioning

confidence: 99%

Gait Analysis of Healthy Rhesus Monkeys Using a Pressure-sensing Walkway System

Won

Kim

Yeo

et al. 2020

Preprint

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Background: Gait analysis in non-human primate models has been performed to elucidate the neural systems involved in controlling quadrupedal locomotor behavior. This study aimed to use a pressure-sensing walkway to identify characteristics of species-specific quadrupedal locomotion in rhesus monkeys. A total of nine healthy adult female rhesus monkeys (Macaca mulatta) were used for gait analysis. We measured the temporo-spatial and kinetic parameters of quadrupedal gait using a custom-built pressure-sensing walkway and compared the left- and right-side parameters to assess the symmetry of the gait pattern. Results: All temporo-spatial and kinetic parameter values showed no significant differences among the nine rhesus monkeys for both the forelimbs and hindlimbs. However, significant differences were observed between forelimb and hindlimb kinetic parameters such as peak vertical force, vertical impulse, and the percentage of body weight distribution. All kinetic parameter values were higher for the forelimbs than for the hindlimbs. These data indicated that the center of gravity in healthy rhesus monkeys is located at the forelimbs rather than at the hindlimbs while walking. Furthermore, the symmetry indices considered for symmetric gait pattern showed a low variability. Most median symmetry index values were nearly zero, indicating no difference between the right and left sides. Conclusions: This study described valid methods for assessing gait parameters and demonstrated rhesus-specific characteristics of quadrupedal locomotion, providing a basis for the assessment of gait normality in rhesus monkeys.

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Robot‐assisted mechanical therapy attenuates stroke‐induced limb skeletal muscle injury

Cited by 17 publications

References 49 publications

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

Phytoestrogen isoflavone intervention to engage the neuroprotective effect of glutamate oxaloacetate transaminase against stroke

Gait Analysis of Healthy Rhesus Monkeys Using a Pressure-sensing Walkway System

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