Neurovascular unit remodelling in the subacute stage of stroke recovery

Lake, Evelyn M. R.; Bazzigaluppi, Paolo; Mester, James R.; Thomason, Lynsie A.M.; Janik, Rafal; Brown, Mary Elizabeth; McLaurin, JoAnne; Carlen, Peter L.; Corbett, Dale; Stanisz, Greg J.; Stefanović, Bojana

doi:10.1016/j.neuroimage.2016.09.016

Cited by 43 publications

(48 citation statements)

References 53 publications

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“…The definition of "subacute" was limited to within 1-6 months after onset in consideration of the influence of spontaneous recovery (46) and relatively stable blood flow (47). In this stage, patients were able to receive more intensive training, i.e., 2-3 h per day.…”

Section: Discussionmentioning

confidence: 99%

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training

Zan

et al. 2020

Front. Neurol.

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Brain computer interface (BCI)-based training is promising for the treatment of stroke patients with upper limb (UL) paralysis. However, most stroke patients receive comprehensive treatment that not only includes BCI, but also routine training. The purpose of this study was to investigate the topological alterations in brain functional networks following comprehensive treatment, including BCI training, in the subacute stage of stroke. Twenty-five hospitalized subacute stroke patients with moderate to severe UL paralysis were assigned to one of two groups: 4-week comprehensive treatment, including routine and BCI training (BCI group, BG, n = 14) and 4-week routine training without BCI support (control group, CG, n = 11). Functional UL assessments were performed before and after training, including, Fugl-Meyer Assessment-UL (FMA-UL), Action Research Arm Test (ARAT), and Wolf Motor Function Test (WMFT). Neuroimaging assessment of functional connectivity (FC) in the BG was performed by resting state functional magnetic resonance imaging. After training, as compared with baseline, all clinical assessments (FMA-UL, ARAT, and WMFT) improved significantly (p < 0.05) in both groups. Meanwhile, better functional improvements were observed in FMA-UL (p < 0.05), ARAT (p < 0.05), and WMFT (p < 0.05) in the BG. Meanwhile, FC of the BG increased across the whole brain, including the temporal, parietal, and occipital lobes and subcortical regions. More importantly, increased inter-hemispheric FC between the somatosensory association cortex and putamen was strongly positively associated with UL motor function after training. Our findings demonstrate that comprehensive rehabilitation, including BCI training, can enhance UL motor function better than routine training for subacute stroke patients. The reorganization of brain functional networks topology in subacute stroke patients allows for increased coordination between the Wu et al.Clinical and rs-fMRI Study multi-sensory and motor-related cortex and the extrapyramidal system. Future long-term, longitudinal, controlled neuroimaging studies are needed to assess the effectiveness of BCI training as an approach to promote brain plasticity during the subacute stage of stroke.

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Section: Discussionmentioning

confidence: 99%

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training

Zan

et al. 2020

Front. Neurol.

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“…The neurovascular unit a complex interplay of biochemical and molecular mechanisms involving practically any cell type of the brain . After ischemic stroke, disruption of the normal vasculature leads to neuronal ischemia and cascades of pro‐inflammatory responses that eventually exacerbates ischemic brain injury . Angiogenesis, the growth of new blood vessels, could be interpreted as a natural defense mechanism helping to restore oxygen and nutrient supply to the affected brain tissue .…”

Section: The Role Of Neuroinflammation In Multiple Brain Repair Mechamentioning

confidence: 99%

“…In this context, angiogenesis and structure reconstruction are necessary and important steps towards function restoration . Soon after ischemic attack, endothelial cells proliferate and migrate to the impaired region under the regulation of angiogenic growth factors to form a new microvasculature structure, while the perilesional vascular reactivity remains elevated until 21 days after stroke . Angiogenesis relies heavily on the coordination of proangiogenic and antiangiogenic factors, in which the neuro‐immune crosstalk by microglia, astrocytes, and peripheral immune cells is actively involved (Figure ).…”

Section: The Role Of Neuroinflammation In Multiple Brain Repair Mechamentioning

confidence: 99%

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

et al. 2018

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Stroke is the world's leading cause of disability with limited brain repair treatments which effectively improve long-term neurological deficits. The neuroinflammatory responses persist into the late repair phase of stroke and participate in all brain repair elements, including neurogenesis, angiogenesis, synaptogenesis, remyelination and axonal sprouting, shedding new light on post-stroke brain recovery. Resident brain glial cells, such as astrocytes not only contribute to neuroinflammation after stroke, but also secrete a wide range of trophic factors that can promote post-stroke brain repair. Alternatively, activated microglia, monocytes, and neutrophils in the innate immune system, traditionally considered as major damaging factors after stroke, have been suggested to be extensively involved in brain repair after stroke. The adaptive immune system may also have its bright side during the late regenerative phase, affecting the immune suppressive regulatory T cells and B cells. This review summarizes the recent findings in the evolving role of neuroinflammation in multiple post-stroke brain repair mechanisms and poses unanswered questions that may generate new directions for future research and give rise to novel therapeutic targets to improve stroke recovery.

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“…Thus, ECM integrity is essential for sustained synaptic signaling and neuronal circuit stability. Upon brain injury induced by ischemic stroke, the ECM is rapidly degraded within a few hours (Härtig et al, 2017), and it remains partly decomposed after one week in lesion-surrounding brain areas (Dzyubenko et al, 2018), in which neuronal network activity is compromised (Clarkson et al, 2010;Lake et al, 2017). Whether ECM depletion contributes to the altered neuronal network activity after brain injury and how it influences synaptic plasticity remains to be identified.…”

Section: Introductionmentioning

confidence: 99%

Extracellular matrix supports excitation-inhibition balance in neuronal networks by stabilizing inhibitory synapses

Dzyubenko

Fleischer

Manrique-Castano

et al. 2020

Preprint

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Maintaining the balance between excitation and inhibition is essential for the appropriate control of neuronal network activity. Sustained excitation-inhibition (E-I) balance relies on the orchestrated adjustment of synaptic strength, neuronal activity and network circuitry. While growing evidence indicates that extracellular matrix (ECM) of the brain is a crucial regulator of neuronal excitability and synaptic plasticity, it remains unclear whether and how ECM contributes to neuronal circuit stability. Here we demonstrate that the integrity of ECM supports the maintenance of E-I balance by retaining inhibitory connectivity. Depletion of ECM in mature neuronal networks preferentially decreases the density of inhibitory synapses and the size of individual inhibitory postsynaptic scaffolds. After ECM depletion, inhibitory synapse strength homeostatically increases via the reduction of presynaptic GABAB receptors. However, the inhibitory connectivity reduces to an extent that inhibitory synapse scaling is no longer efficient in controlling neuronal network state. Our results indicate that the brain ECM preserves the balanced network state by stabilizing inhibitory control.

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Neurovascular unit remodelling in the subacute stage of stroke recovery

Cited by 43 publications

References 53 publications

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training

Brain Functional Networks Study of Subacute Stroke Patients With Upper Limb Dysfunction After Comprehensive Rehabilitation Including BCI Training

The evolving role of neuro‐immune interaction in brain repair after cerebral ischemic stroke

Extracellular matrix supports excitation-inhibition balance in neuronal networks by stabilizing inhibitory synapses

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