It doesn't sound like anything in here describes anything useful to stroke recovery, but have your doctor check it out
Therapeutic Opportunities and Delivery Strategies for Brain Revascularization in Stroke, Neurodegeneration, and Aging
Abstract
Central nervous system (CNS) diseases, especially acute ischemic events and neurodegenerative disorders, constitute a public health problem with no effective treatments to allow a persistent solution. Failed therapies targeting neuronal recovery have revealed the multifactorial and intricate pathophysiology underlying such CNS disorders as ischemic stroke, Alzheimeŕs disease, amyotrophic lateral sclerosis, vascular Parkisonism, vascular dementia, and aging, in which cerebral microvasculature impairment seems to play a key role. In fact, a reduction in vessel density and cerebral blood flow occurs in these scenarios, contributing to neuronal dysfunction and leading to loss of cognitive function. In this review, we provide an overview of healthy brain microvasculature structure and function in health and the effect of the aforementioned cerebral CNS diseases. We discuss the emerging new therapeutic opportunities, and their delivery approaches, aimed at recovering brain vascularization in this context.
Significance Statement The lack of effective treatments, mainly focused on neuron recovery, has prompted the search of other therapies to treat cerebral central nervous system diseases. The disruption and degeneration of cerebral microvasculature has been evidenced in neurodegenerative diseases, stroke, and aging, constituting a potential target for restoring vascularization, neuronal functioning, and cognitive capacities by the development of therapeutic pro-angiogenic strategies.
I. Introduction
Neurologic disorders are the second leading cause of death and the principal cause of disability in the world (GBD 2015 Neurologic Disorders Collaborator Group, 2017). Increasing life expectancy and population growth worldwide imply that more and more people are reaching ages in which neurologic disorders are more prevalent. The rising incidence and prevalence of these related central nervous system (CNS) diseases have an important socioeconomic impact, so it becomes a real problem not only for patients and families but also for the economy and healthcare systems (Harper, 2014; Wimo et al., 2020). There are no curative pharmacological treatments able to attain a complete neurovascular recovery in CNS diseases; they can only slow down the neurologic degenerative processes. This scenario underscores the difficulty of current pharmacological drugs to target and efficiently act in the brain. One of the main obstacles that lacks the success of such therapies is the blood-brain-barrier (BBB), along with other factors that must be taken into consideration, such as the presence of other extracellular and intracellular barriers and the complexity of the neurovascular network with interactions at several levels. For this reason, huge research efforts are being conducted to find and develop novel therapeutic strategies for CNS diseases (Niu et al., 2019; Poovaiah et al., 2018; Teleanu et al., 2019).
A few years ago, neuroscientists considered the brain as a dichotomized organ comprised of brain cells and cerebral blood vessels, with no relationship among these two entities. Nowadays however, the scientific community is aware of the close connection established and required between neuronal and vascular CNS cells for correct brain functioning. The brain is one of the most highly perfused organs in the body; in fact, nearly every neuron has its own capillary (Zlokovic, 2005), highlighting the pivotal relationship between the neuronal and vascular systems, called the neurovascular network. The neurovascular network in CNS is responsible for supplying the 20% of the cardiac output carrying oxygen and nutrients to the brain (Iadecola, 2013) and thus contributing to a healthy neurologic function. That is why lack of this supply, caused by vessel damage or degeneration, could have a major role in the pathogenesis of CNS diseases. Consequently, it is not surprising that the cognitive impairment that occurs in many CNS diseases could be related to cerebrovascular disruptions, mainly at the microvasculature level, and cerebral blood flow reduction, as in the case of ischemic stroke, amyotrophic lateral sclerosis (ALS), Alzheimeŕs disease (AD), vascular Parkisonism (VP), vascular dementia (VaD) and aging, which will be described in depth in section III, Vascular Disorders in Brain CNS Diseases.
This review provides an overview of the cellular and molecular mechanisms needed to manage the cerebral microvasculature, as well as an up-to-date perspective of CNS diseases related to cerebral microvasculature damage or deterioration, as is the case of ischemic stroke, Alzheimeŕs disease (AD), amyotrophic lateral sclerosis (ALS), vascular Parkisonism (VP), vascular dementia (VaD) and aging, all of which are associated with cognitive impairment. In particular, we describe evidence for microvasculature regeneration as a form of neurologic and cognitive function improvement by looking at progress in the identification of potential therapeutic pro-angiogenic factors and focusing on the nanotechnological approaches, advanced opportunities, and the administration strategies employed.
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