Promoting Neurological Recovery in the Post-Acute Stroke Phase: Benefits and Challenges

Abstract

Background: Profound cellular and biochemical remodeling processes occur in the brain following an ischemic stroke, raising the possibility that we may be able to promote neurological recovery by harnessing the brain's endogenous recovery processes with pharmacological or cell-based therapies. There is a compelling body of evidence that cerebral plasticity and neurological recovery can be stimulated in the post-acute ischemic brain in this manner. Summary: This overview of neurorestorative therapies highlights the main challenges in their development, and summarizes the implications of these findings to stroke patients. Key Message: Neurorestorative therapies are a highly promising avenue of treatment for the restitution of neuronal networks damaged by stroke. Clinical Implications: The key supporting data have so far been obtained using in vivo models in animals, underscoring the need to validate these findings in humans. For human studies, several potentially confounding variables should be kept in mind, including age, and the presence of risk factors and comorbidities (such as hyperlipidemia and diabetes). Stroke patients vary considerably in age and genetic background, as well as in the etiology, localization and size of brain infarcts. The choice of patient population is a critical factor in the success of clinical trials, as patient heterogeneity could mask any potential therapeutic benefits.

Paradigm Shift to Neuroimmunomodulation for Translational Neuroprotection in Stroke

“…However, the pure blockade of a single inflammatory mechanism has led to disappointing results, being most mediators endowed with dualistic effects on the progression of ischemic brain damage (Amantea et al, 2014 ). This is consistent with the ability of the brain to trigger regenerative responses that are essential for spontaneous recovery and involve cell genesis, axon growth, and synaptic modulation (Chu et al, 2012 ; Hermann and Chopp, 2014 ; Felling and Song, 2015 ). In this context, astrocytes, microglia, and monocytes/macrophages are among the most potent modulators of brain repair/regeneration (Amantea et al, 2015 ; Liu and Chopp, 2016 ).…”

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

“…Motor network reorganization after stroke is time-and activity-dependent (4). Hebbian plasticity describes the phenomenon of coincident activation of pre-and post-synaptic neurons, leading to a reinforcement of synaptic strength, finally resulting in increased and more reliable communication between the activated neurons (5,6). The potential relevance of this concept in behavioral change is particularly wellillustrated in the context of stroke rehabilitation (7).…”

Safety and efficacy of recovery-promoting drugs for motor function after stroke: A systematic review of randomized controlled trials

“…As both reviews targeted singular drug classes, neither could provide judgement comparing the outcomes of the drugs with each other. To address this gap, the aim of this systematic review was to investigate the efficacy and safety of drug interventions trialled to enhance motor recovery post-stroke (3,4).…”

“…As many people lack access to timesensitive stroke interventions targeting prevention and reperfusion, drug interventions that mediate recovery beyond the window for effective reperfusion are important research targets. The treatment window for recovery-promoting drugs (RPD) ranges from days to years post-stroke, increasing the potential for survivors to be eligible, and benefit from treatment (3)(4)(5). Whilst rehabilitation has been proven to be of great benefit, RPDs may have a place in enhancing recovery in instances where stroke survivors receive little therapy and have low levels of physical activity (6).…”