The Role of Noninvasive Techniques in Stroke Therapy

Noninvasive techniques such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have provided insight into understanding how neural connections are altered in consequence to cerebrovascular injury. The first part of this review will briefly survey some of the methodological issues and limitations related to noninvasive poststroke motor recovery studies. The second section will investigate some of the different neural mechanisms that underlie neurorehabilitation in stroke patients. The third part will explore our current understanding of motor memory processing, describe the neural structures that subserve motor memory consolidation, and discuss the current literature related to memory reconsolidation in healthy adults. Lastly, this paper will suggest the potential therapeutic applications of integrating noninvasive tools with memory consolidation and reconsolidation theories to enhance motor recovery. The overall objective of this work is to demonstrate how noninvasive technologies have been utilized in the multidisciplinary field of clinical behavioral neuroscience and to highlight their potential to be employed as clinical tools to promote individualized motor recovery in stroke patients

The role of noninvasive techniques in stroke therapy.

Noninvasive techniques such as functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) have provided insight into understanding how neural connections are altered in consequence to cerebrovascular injury. The first part of this review will briefly survey some of the methodological issues and limitations related to noninvasive poststroke motor recovery studies. The second section will investigate some of the different neural mechanisms that underlie neurorehabilitation in stroke patients. The third part will explore our current understanding of motor memory processing, describe the neural structures that subserve motor memory consolidation, and discuss the current literature related to memory reconsolidation in healthy adults. Lastly, this paper will suggest the potential therapeutic applications of integrating noninvasive tools with memory consolidation and reconsolidation theories to enhance motor recovery. The overall objective of this work is to demonstrate how noninvasive technologies have been utilized in the multidisciplinary field of clinical behavioral neuroscience and to highlight their potential to be employed as clinical tools to promote individualized motor recovery in stroke patients.Peer Reviewe

Restorative Therapies after Stroke: Drugs, Devices and Robotics

Restorative therapies aim to improve outcome and function by promoting plasticity within a therapeutic time window between days to weeks to years. In this article, the mechanisms by which cell-based, pharmacological and robotic treatments stimulate endogenous brain remodelling after stroke, particularly neurogenesis, axonal plasticity and white-matter integrity are described with a brief outline of the potential of neuroimaging (fMRI) techniques. Stem cells aid stroke recovery via mechanisms depending on the type of cells used. Transplanted embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and neural stem cells (NSCs) can replace the missing brain cells in the Infarcted area, while adult stem cells, such as mesenchymal stem cells or multipotent stromal cells (MSCs) and MNCs, provide trophic support to enhance self-repair systems such as endogenous neurogenesis. Most preclinical studies of stem cell therapy for stroke have emphasized the need to enhance self-repair systems rather than to replace lost cells, regardless of the type of cells used. Noninvasive brain stimulation (NIBS) provides a valuable tool for interventional neurophysiology by modulating brain activity in a specific distributed, cortico-subcortical network. The two most commonly used techniques for noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). The article also discusses the potential role and current evidence for the use of pharmacological therapy, robotics and specific forms of physiotherapy regimes in optimizing stroke recovery. Neurorestoration is a concept that has been proven emphatically in several experimental models and clinical studies of stroke. Elucidating the underlying mechanisms of cell-based, pharmacological and rehabilitative therapies is of primary interest and crucial for translation of treatments to clinical use. The knowledge must provide an impetus for the development of superior, advanced and cost effective neuro restorative interventions that will enhance stroke recovery. Keywords : Cerebral stroke, stroke therapy, functional neuroimaging

The future of ischemic stroke: flow from prehospital neuroprotection to definitive reperfusion.

Recent advances in ischemic stroke enable a seamless transition of the patient flow from the prehospital setting to definitive reperfusion, without the arbitrary separation of therapeutic phases of ischemia based on time alone. In 2013, the framework to understand and directly address the pathophysiology of cerebral blood flow that determines the timeline or evolution of ischemia in an individual case is given. This continuum of flow and the homeostasis of brain perfusion balanced by collaterals may be captured with serial imaging. Ongoing imaging core laboratory activities permit large-scale measurement of angiographic and tissue biomarkers of ischemia. Prehospital neuroprotection has become a reality and may be combined with revascularization therapies. Recent studies confirm that image-guided thrombolysis may be achieved without restrictive time windows. Baseline imaging patterns may be used to predict response to therapy and serial imaging may discern recanalization and reperfusion. Advanced techniques, such as arterial spin-labeled MRI, may also report hyperperfusion associated with hemorrhagic transformation. Endovascular therapies, including novel stent retriever devices, may augment revascularization and angiographic core laboratories may define optimal reperfusion. Serial evaluation of collaterals and reperfusion may identify definitive reperfusion linked with good clinical outcome rather than imposing arbitrary definitions of effective recanalization. Reperfusion injury and hemorrhagic transformation of various types may be detailed to explain clinical outcomes. Similar approaches may be used in intracranial atherosclerosis where flow, and not the degree of luminal stenosis, is paramount. Fractional flow may now be measured with computational fluid dynamics to identify high-risk lesions that require revascularization to restore the equilibrium of antegrade and collateral perfusion. Serial perfusion imaging of such cases may also illustrate inadequate cerebral blood volume gradients that may be more informative than blood flow delay alone. In sum, the growing understanding of collateral perfusion throughout all stages of ischemic stroke provides a framework for the future of ischemic stroke

Drug delivery in overcoming the blood-brain barrier: role of nasal mucosal grafting

The blood–brain barrier (BBB) plays a fundamental role in protecting and maintaining the homeostasis of the brain. For this reason, drug delivery to the brain is much more difficult than that to other compartments of the body. In order to bypass or cross the BBB, many strategies have been developed: invasive techniques, such as temporary disruption of the BBB or direct intraventricular and intracerebral administration of the drug, as well as noninvasive techniques. Preliminary results, reported in the large number of studies on the potential strategies for brain delivery, are encouraging, but it is far too early to draw any conclusion about the actual use of these therapeutic approaches. Among the most recent, but still pioneering, approaches related to the nasal mucosa properties, the permeabilization of the BBB via nasal mucosal engrafting can offer new potential opportunities. It should be emphasized that this surgical procedure is quite invasive, but the implication for patient outcome needs to be compared to the gold standard of direct intracranial injection, and evaluated whilst keeping in mind that central nervous system diseases and lysosomal storage diseases are chronic and severely debilitating and that up to now no therapy seems to be completely successful

A Calibrated Method of Massage Therapy Decreases Systolic Blood Pressure Concomitant With Changes in Heart Rate Variability in Male Rats.

ObjectiveThe purpose of this study was to develop a method for applying calibrated manual massage pressures by using commonly available, inexpensive sphygmomanometer parts and validate the use of this approach as a quantitative method of applying massage therapy to rodents.MethodsMassage pressures were monitored by using a modified neonatal blood pressure (BP) cuff attached to an aneroid gauge. Lightly anesthetized rats were stroked on the ventral abdomen for 5 minutes at pressures of 20 mm Hg and 40 mm Hg. Blood pressure was monitored noninvasively for 20 minutes following massage therapy at 5-minute intervals. Interexaminer reliability was assessed by applying 20 mm Hg and 40 mm Hg pressures to a digital scale in the presence or absence of the pressure gauge.ResultsWith the use of this method, we observed good interexaminer reliability, with intraclass coefficients of 0.989 versus 0.624 in blinded controls. In Long-Evans rats, systolic BP dropped by an average of 9.86% ± 0.27% following application of 40 mm Hg massage pressure. Similar effects were seen following 20 mm Hg pressure (6.52% ± 1.7%), although latency to effect was greater than at 40 mm Hg. Sprague-Dawley rats behaved similarly to Long-Evans rats. Low-frequency/high-frequency ratio, a widely-used index of autonomic tone in cardiovascular regulation, showed a significant increase within 5 minutes after 40 mm Hg massage pressure was applied.ConclusionsThe calibrated massage method was shown to be a reproducible method for applying massage pressures in rodents and lowering BP

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

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

Focal Spot, Winter 2008/2009

https://digitalcommons.wustl.edu/focal_spot_archives/1110/thumbnail.jp