Dataset Information

Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke.

ABSTRACT: It has recently been identified that after motor cortex stroke, the ability of microglia processes to respond to local damage cues is lost from the thalamus, a major site of secondary neurodegeneration (SND). In this study, we combine a photothrombotic stroke model in mice, acute slice and fluorescent imaging to analyse the loss of microglia process responsiveness. The peri-infarct territories and thalamic areas of SND were investigated at time-points 3, 7, 14, 28 and 56 days after stroke. We confirmed the highly specific nature of non-responsive microglia processes to sites of SND. Non-responsiveness was at no time observed at the peri-infarct but started in the thalamus seven days post-stroke and persisted for 56 days. Loss of directed process extension is not a reflection of general functional paralysis as phagocytic function continued to increase over time. Additionally, we identified that somal P₂Y₁₂ was present on non-responsive microglia in the first two weeks after stroke but not at later time points. Finally, both classical microglia activation and loss of process extension are highly correlated with neuronal damage. Our findings highlight the importance of microglia, specifically microglia dynamic functions, to the progression of SND post-stroke, and their potential relevance as modulators or therapeutic targets during stroke recovery.

SUBMITTER: Kluge MG

PROVIDER: S-EPMC6893987 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke.

Kluge Murielle G MG Abdolhoseini Mahmoud M Zalewska Katarzyna K Ong Lin Kooi LK Johnson Sarah J SJ Nilsson Michael M Walker Frederick R FR

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20180911 12

It has recently been identified that after motor cortex stroke, the ability of microglia processes to respond to local damage cues is lost from the thalamus, a major site of secondary neurodegeneration (SND). In this study, we combine a photothrombotic stroke model in mice, acute slice and fluorescent imaging to analyse the loss of microglia process responsiveness. The peri-infarct territories and thalamic areas of SND were investigated at time-points 3, 7, 14, 28 and 56 days after stroke. We co ...[more]

PMID: 30204044

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Project description:Posture and movement planning, preparation, and execution of a goal-directed reaching movement are impaired in individuals with stroke. No studies have shown whether the deficits are generally impaired or are specific to the lesioned hemisphere/paretic arm. This study utilized StartReact (SR) responses elicited by loud acoustic stimuli (LAS) to investigate the preparation and execution of anticipatory postural adjustments (APAs) and reach movement response during both paretic and nonparetic arm reaching in individuals with stroke and in age-matched healthy controls. Subjects were asked to get ready after receiving a warning cue and to reach at a "go" cue. An LAS was delivered at -500, -200, and 0 ms relative to the go cue. Kinetic, kinematic, and electromyographic data were recorded to characterize APA-reach movement responses. Individuals with stroke demonstrated systemwide deficits in posture and in movement planning, preparation, and execution of APA-reach sequence as shown by significant reduction in the incidence of SR response and impaired APA-reach performance, with greater deficits during paretic arm reaching. Use of trunk compensation strategy as characterized by greater involvement of trunk and pelvic rotation was utilized by individuals with stroke during paretic arm reaching compared with nonparetic arm reaching and healthy controls. Our findings have implications for upper extremity and postural control, suggesting that intervention should include training not only for the paretic arm but also for the nonparetic arm with simultaneous postural control requirements to improve the coordination of the APA-reach performance and subsequently reduce instability while functional tasks are performed during standing. NEW & NOTEWORTHY Our study is the first to show that nonparetic arm reaching also demonstrates impairment in posture and movement planning, preparation, and execution when performed during standing by individuals with stroke. In addition, we found compensatory trunk and pelvic rotations were used during a standing reach task for the paretic arms. The findings have clinical implications for upper extremity and postural rehabilitation, suggesting that training should include the nonparetic arms and incorporate simultaneous postural control demands.

Project description:Background: Deficits in interjoint coordination, such as the inability to move out of synergy, are frequent symptoms in stroke subjects with upper limb impairments that hinder them from regaining normal motor function. Kinematic measurements allow a fine-grained assessment of movement pathologies, thereby complementing clinical scales, like the Fugl-Meyer Motor Assessment of the Upper Extremity (FMMA-UE). The study goal was to investigate the effects of the performed task, the tested arm, the dominant affected hand, upper limb function, and age on spatiotemporal parameters of the elbow, shoulder, and trunk. The construct validity of the metrics was examined by relating them with each other, the FMMA-UE, and its arm section. Methods: This is a cross-sectional observational study including chronic stroke patients with mild to moderate upper limb motor impairment. Kinematic measurements were taken using a wearable sensor suit while performing four movements with both upper limbs: (1) isolated shoulder flexion, (2) pointing, (3) reach-to-grasp a glass, and (4) key insertion. The kinematic parameters included the joint ranges of shoulder abduction/adduction, shoulder flexion/extension, and elbow flexion/extension; trunk displacement; shoulder-elbow correlation coefficient; median slope; and curve efficiency. The effects of the task and tested arm on the metrics were investigated using a mixed-model analysis. The validity of metrics compared to clinically measured interjoint coordination (FMMA-UE) was done by correlation analysis. Results: Twenty-six subjects were included in the analysis. The movement task and tested arm showed significant effects (p < 0.05) on all kinematic parameters. Hand dominance resulted in significant effects on shoulder flexion/extension and curve efficiency. The level of upper limb function showed influences on curve efficiency and the factor age on median slope. Relations with the FMMA-UE revealed the strongest and significant correlation for curve efficiency (r = 0.75), followed by shoulder flexion/extension (r = 0.68), elbow flexion/extension (r = 0.53), and shoulder abduction/adduction (r = 0.49). Curve efficiency additionally correlated significantly with the arm subsection, focusing on synergistic control (r = 0.59). Conclusion: The kinematic parameters of the upper limb after stroke were influenced largely by the task. These results underpin the necessity to assess different relevant functional movements close to real-world conditions rather than relying solely on clinical measures. Study Registration: clinicaltrials.gov, identifier NCT03135093 and BASEC-ID 2016-02075.

Dataset Information

Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke.

Publications

Spatiotemporal analysis of impaired microglia process movement at sites of secondary neurodegeneration post-stroke.

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