Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Alia, Claudia; Spalletti, Cristina; Lai, Stefano; Panarese, Alessandro; Lamola, Giuseppe; Bertolucci, Federica; Vallone, Fabio; Garbo, Angelo Di; Chisari, Carmelo; Micera, Silvestro; Caleo, Matteo

doi:10.3389/fncel.2017.00076

Cited by 173 publications

(130 citation statements)

References 250 publications

(341 reference statements)

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“…Stroke patients usually demonstrate a degree of spontaneous improvement in the subacute phase, which can be further enhanced with appropriate prolonged rehabilitation. The observed functional outcomes appear to be consistent with partial rewiring of surviving neural networks and recruitment of intact synapses, which tends to occur contralateral, but also ipsilateral to the lesion (Alia et al., ; Askim, Indredavik, & Haberg, ; Askim, Indredavik, Vangberg, & Haberg, ; Cramer & Chopp, ; Harrison, Silasi, Boyd, & Murphy, ). Depending on the severity of the stroke and the type of clinical treatment and/or rehabilitation paradigm, these mechanisms may account for spontaneous functional recovery which may be observed in certain stroke patients 30–90 days post‐ischaemia, especially with regard to alleviation of language and cognitive impairments, but also motor impairments such as voluntary maximum arm extension (Grefkes & Ward, ).…”

Section: Introductionmentioning

confidence: 58%

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Sandvig

Augestad

Håberg

et al. 2018

Eur J of Neuroscience

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Neuroplasticity after ischaemic injury involves both spontaneous rewiring of neural networks and circuits as well as functional responses in neurogenic niches. These events involve complex interactions with activated microglia, which evolve in a dynamic manner over time. Although the exact mechanisms underlying these interactions remain poorly understood, increasing experimental evidence suggests a determining role of pro- and anti-inflammatory microglial activation profiles in shaping both synaptogenesis and neurogenesis. While the inflammatory response of microglia was thought to be detrimental, a more complex profile of the role of microglia in tissue remodelling is emerging. Experimental evidence suggests that microglia in response to injury can rapidly modify neuronal activity and modulate synaptic function, as well as be beneficial for the proliferation and integration of neural progenitor cells (NPCs) from endogenous neurogenic niches into functional networks thereby supporting stroke recovery. The manner in which microglia contribute towards sculpting neural synapses and networks, both in terms of activity-dependent and homeostatic plasticity, suggests that microglia-mediated pro- and/or anti-inflammatory activity may significantly contribute towards spontaneous neuronal plasticity after ischaemic lesions. In this review, we first introduce some of the key cellular and molecular mechanisms underlying neuroplasticity in stroke and then proceed to discuss the crosstalk between microglia and endogenous neuroplasticity in response to brain ischaemia with special focus on the engagement of synapses and neural networks and their implications for grey matter integrity and function in stroke repair.

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Section: Introductionmentioning

confidence: 58%

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Sandvig

Augestad

Håberg

et al. 2018

Eur J of Neuroscience

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“…with reorganization of the connections that is modulated/influenced by experiences [7,8]. Plastic rewiring involve the perilesional tissue and injured hemisphere, the contralateral brain, subcortical, and spinal regions [9]. Increasing therapy dosage, intensity, number of repetition, execution of task‐oriented exercises, and combining top‐down and bottom‐up approaches, can promote plasticity and functional recovery [10‐12].…”

Section: Introductionmentioning

confidence: 99%

Exoskeleton and End‐Effector Robots for Upper and Lower Limbs Rehabilitation: Narrative Review

Molteni

Gasperini

Cannaviello

et al. 2018

PM&R

196

143

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Recovery of upper and lower limbs function is essential to reach independence in daily activities in patients with upper motor neuron syndrome (UMNS). Rehabilitation can provide a guide for motor recovery influencing the neurobiology of neuronal plasticity providing controlled, repetitive, and variable patterns. Increasing therapy dosage, intensity, number of repetition, execution of task‐oriented exercises, and combining top‐down and bottom‐up approaches can promote plasticity and functional recovery. Robotic exoskeletons for upper and lower limbs, based on the principle of motor learning, have been introduced in neurorehabilitation. In this narrative review, we provide an overview of literature published on exoskeleton devices for upper and lower limb rehabilitation in patients with UMNS; we summarized the available current research evidence and outlined the new challenges that neurorehabilitation and bioengineering will have to face in the upcoming years. Robotic treatment should be considered a rehabilitation tool useful to generate a more complex, controlled multisensory stimulation of the patient and useful to modify the plasticity of neural connections through the experience of movement. Efficacy and efficiency of robotic treatment should be defined starting from intensity, complexity, and specificity of the robotic exercise, that are related to human‐robot interaction in terms of motion, emotion, motivation, meaning of the task, feedback from the exoskeleton, and fine motion assistance. Duration of a single session, global period of the treatment, and the timing for beginning of robotic treatment are still open questions. There is the need to evaluate and individualize the treatment according to patient's characteristics. Robotic devices for upper and lower limbs open a window to define therapeutic modalities as possible beneficial drug, able to boost biological, neurobiological, and epigenetic changes in central nervous system. We need to implement large and innovative research programs to answer these issues in the near future.

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“…The interplay between growth factors and microvascular cells prompts axonal sprouting and facilitates functional recovery [12]. The endogenous remodeling of the central nervous system is restrictive regarding the induction of complete restoration of neurological function; however, the elicitation of the endogenous restorative mechanism may represent a therapeutic avenue for this condition [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Sequential Transcriptome Changes in the Penumbra after Ischemic Stroke

Choi

Yun

Kim

et al. 2019

IJMS

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To investigate the changes in the expression of specific genes that occur during the acute-to-chronic post-stroke phase, we identified differentially expressed genes (DEGs) between naive cortical tissues and peri-infarct tissues at 1, 4, and 8 weeks after photothrombotic stroke. The profiles of DEGs were subjected to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology analyses, followed by string analysis of the protein–protein interactions (PPI) of the products of these genes. We found 3771, 536, and 533 DEGs at 1, 4, and 8 weeks after stroke, respectively. A marked decrease in biological–process categories, such as brain development and memory, and a decrease in neurotransmitter synaptic and signaling pathways were observed 1 week after stroke. The PPI analysis showed the downregulation of Dlg4, Bdnf, Gria1, Rhoa, Mapk8, and glutamatergic receptors. An increase in biological–process categories, including cell population proliferation, cell adhesion, and inflammatory responses, was detected at 4 and 8 weeks post-stroke. The KEGG pathways of complement and coagulation cascades, phagosomes, antigen processing, and antigen presentation were also altered. CD44, C1, Fcgr2b, Spp1, and Cd74 occupied a prominent position in network analyses. These time-dependent changes in gene profiles reveal the unique pathophysiological characteristics of stroke and suggest new therapeutic targets for this disease.

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Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Cited by 173 publications

References 250 publications

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Neuroplasticity in stroke recovery. The role of microglia in engaging and modifying synapses and networks

Exoskeleton and End‐Effector Robots for Upper and Lower Limbs Rehabilitation: Narrative Review

Sequential Transcriptome Changes in the Penumbra after Ischemic Stroke

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