Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway

Baba, Tetsuya; Kameda, Masahiro; Yasuhara, Takao; Morimoto, T; Kondo, Akihiko; Shingo, Tetsuro; Tajiri, Naoki; Wang, Feifei; Miyoshi, Yasuyuki; Borlongan, Cesario V.; Matsumae, Mitsunori; Date, Isao

doi:10.1161/strokeaha.109.563627

Cited by 120 publications

(126 citation statements)

References 29 publications

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“…Evidence to support specific mechanisms underlying the effects of open-loop electrical stimulation of the cortex on recovery is largely correlative but includes motor map reorganization, increased dendritic length and spine density, cell proliferation and cell migration in the subventricular zone, receptor subunit expression, activation of antiapoptotic cascades, increased neurotrophic factors, enhanced angiogenesis, and proliferation of inflammatory cells (20,21,(24)(25)(26)(27)(28). Because the number of stimulus pulses was similar in the ADS and OLS groups in the present study, it is reasonable to conclude that if electrical stimulation promoted proliferative processes, the effects were the same in the two groups.…”

Section: Differential Mechanisms Underlying the Effects Of Ols And Admentioning

confidence: 99%

Restoration of function after brain damage using a neural prosthesis

Guggenmos

Azin

Barbay

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

195

182

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Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities. After implantation of microelectrodes in cerebral cortex, a neural prosthesis discriminated action potentials (spikes) in premotor cortex that triggered electrical stimulation in somatosensory cortex continuously over subsequent weeks. Within 1 wk, while receiving spike-triggered stimulation, rats showed substantially improved reaching and grasping functions that were indistinguishable from prelesion levels by 2 wk. Post hoc analysis of the spikes evoked by the stimulation provides compelling evidence that the neural prosthesis enhanced functional connectivity between the two target areas. This proofof-concept study demonstrates that neural interface systems can be used effectively to bridge damaged neural pathways functionally and promote recovery after brain injury.brain-machine-brain interface | neural plasticity | traumatic brain injury | closed-loop | long-term potentiation T he view of the brain as a collection of independent anatomical modules, each with discrete functions, is currently undergoing radical change. New evidence from neurophysiological and neuroanatomical experiments in animals, as well as neuroimaging studies in humans, now suggests that normal brain function can be best appreciated in the context of the complex arrangements of functional and structural interconnections among brain areas. Although mechanistic details are still under refinement, synchronous discharge of neurons in widespread areas of the cerebral cortex appears to be an emergent property of neuronal networks that functionally couple remote locations (1). It is now recognized that not only are discrete regions of the brain damaged in injury or disease but, perhaps more importantly, the interconnections among uninjured areas are disrupted, potentially leading to many of the functional impairments that persist after brain injury (2). Likewise, plasticity of brain interconnections may partially underlie recovery of function after injury (3).Technological efforts to restore brain function after injury have focused primarily on modulating the excitability of focal regions in uninjured parts of the brain (4). Purportedly, increasing the excitability of neurons involved in adaptive plasticity expands the neural substrate potentially involved in functional recovery. However, no methods are yet available to alter the functional connectivity between spared brain regions directly, with the intent to restore normal communication patterns. The present paper tests the hypothesis that an artificial communication link between uninjured regions of the...

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Section: Differential Mechanisms Underlying the Effects Of Ols And Admentioning

confidence: 99%

Restoration of function after brain damage using a neural prosthesis

Guggenmos

Azin

Barbay

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

195

182

View full text Add to dashboard Cite

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“…88,89 There is now mounting evidence that angiogenesis occurs in concert with neurogenesis and synaptogenesis in experimental models of recovery after ischemic brain injury. 90 These processes take place in response to a disparate range of interventions, from cortical stimulation 91 to antidepressant therapy. 92 Although the time course of angiogenesis and neurogenesis overlaps, many investigators have now concluded that the angiogenesis occurs first and leads to axonal remodeling 93 and neuroblast migration along new blood vessels.…”

Section: Stroke and Neovascularizationmentioning

confidence: 99%

Cerebral Neovascularization in Diabetes: Implications for Stroke Recovery and beyond

Ergul

Abdelsaid

Fouda

et al. 2014

J Cereb Blood Flow Metab

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Neovascularization is an innate physiologic response by which tissues respond to various stimuli through collateral remodeling (arteriogenesis) and new vessel formation from existing vessels (angiogenesis) or from endothelial progenitor cells (vasculogenesis). Diabetes has a major impact on the neovascularization process but the response varies between different organ systems. While excessive angiogenesis complicates diabetic retinopathy, impaired neovascularization contributes to coronary and peripheral complications of diabetes. How diabetes influences cerebral neovascularization remained unresolved until recently. Diabetes is also a major risk factor for stroke and poor recovery after stroke. In this review, we discuss the impact of diabetes, stroke, and diabetic stroke on cerebral neovascularization, explore potential mechanisms involved in diabetes-mediated neovascularization as well as the effects of the diabetic milieu on poststroke neovascularization and recovery, and finally discuss the clinical implications of these effects.

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“…Striatal stimulation enhances migration of neural progenitor cells towards the penumbra and their subsequent differentiation into neurons [80]. In acute models, cortical stimulation may operate by upregulating neurotrophic and angiogenic factors in tandem with suppression of apoptotic cell death [81]. The ability of stimulation to induce neuroprotection may emerge from its capacity to salvage ischemic tissue, promote neural repair, and/or lower cell death to help sustain gains from rehabilitation-a promise that remains to be substantiated in future.…”

Section: Differentiating Between Short-and Long-term Mechanisms Of Comentioning

confidence: 99%

Invasive Neurostimulation in Stroke Rehabilitation

Plow

Machado

2014

Neurotherapeutics

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The last decade has seen a growing interest in adjuvant treatments that synergistically influence mechanisms underlying rehabilitation of paretic upper limb in stroke. One such approach is invasive neurostimulation of spared cortices at the periphery of a lesion. Studies in animals have shown that during training of paretic limb, adjuvant stimulation targeting the peri-infarct circuitry enhances mechanisms of its reorganization, generating functional advantage. Success of early animal studies and clinical reports, however, failed to translate to a phase III clinical trial. As lesions in humans are diffuse, unlike many animal models, peri-infarct circuitry may not be a feasible, or consistent target across most. Instead, alternate mechanisms, such as changing transcallosal inhibition between hemispheres, or reorganization of other viable regions in motor control, may hold greater potential. Here, we review comprehensive mechanisms of clinical recovery and factors that govern which mechanism(s) become operative when. We suggest novel approaches that take into account a patient's initial clinical-functional state, and findings from neuroimaging and neurophysiology to guide to their most suitable mechanism for ideal targeting. Further, we suggest new localization schemes, and bypass strategies that indirectly target peri-lesional circuitry, and methods that serve to counter technical and theoretical challenge in identifying and stimulating such targets at the periphery of infarcts in humans. Last, we describe how stimulation may modulate mechanisms differentially across varying phases of recovery-a temporal effect that may explain missed advantage in clinical trials and help plan for the next stage. With information presented here, future trials would effectively be able to target patient's specific mechanism(s) with invasive (or noninvasive) neurostimulation for the greatest, most consistent benefit. [2], which remains one of the most important predictors of disability and poor quality of life [3]. Disability adds to the costs of disease management that total $74 billion/ year [4]. Developing methods to effectively alleviate residual deficits will reduce health and economic burden of stroke.Several evidence-based rehabilitative approaches have been developed with prominent ones, including neuromuscular electrical stimulation [5], motor learning [6], robotic training [7] constraint-induced movement therapy [8], and bilateral arm training [9], etc. In spite of extensive therapy, recovery is frequently incomplete [10]. There is a critical need for adjuvant strategies that augment rehabilitative outcomes of paretic hand.The last decade has seen a growing interest in the promise of adjuvant treatments that synergistically influence mechanisms associated with rehabilitation. One such approach is invasive neuromodulation, involving electrical stimulation applied to cortical or subcortical targets spared by stroke. By directly stimulating viable targets, it is believed that potential for plasticity underlying reh...

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Electrical Stimulation of the Cerebral Cortex Exerts Antiapoptotic, Angiogenic, and Anti-Inflammatory Effects in Ischemic Stroke Rats Through Phosphoinositide 3-Kinase/Akt Signaling Pathway

Cited by 120 publications

References 29 publications

Restoration of function after brain damage using a neural prosthesis

Restoration of function after brain damage using a neural prosthesis

Cerebral Neovascularization in Diabetes: Implications for Stroke Recovery and beyond

Invasive Neurostimulation in Stroke Rehabilitation

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