Therapeutic Opportunities and Delivery Strategies for Brain Revascularization in Stroke, Neurodegeneration, and Aging

Gallego, Idoia; Villate-Beitia, Ilia; Burgo, Laura Sáenz del; Puras, Gustavo; Pedraz, José Luís

doi:10.1124/pharmrev.121.000418

Cited by 15 publications

(11 citation statements)

References 231 publications

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“…Revascularization is important for structural and functional recovery in ischaemic injury. [ 25 ] Immunostaining of heart sections against the vascular marker CD31 showed that there were few vessels in the PBS group, indicating poor revascularization in these tissues. In comparison, significantly more vascular structures were observed in the HA and NP groups ( Figure ), indicating that HA and NPs promoted myocardial revascularization.…”

Section: Resultsmentioning

confidence: 99%

Cobweb‐Inspired Microenvironment‐Targeting Nanosystem with Sequential Multiple‐Stage Stimulus‐Response Capacity for Ischaemic Tissue Repair

Ding

Xing

Liu

et al. 2023

Adv Funct Materials

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Myocardial ischaemia is pathologically complicated; various changes in intracellular and extracellular microenvironments make it essential to develop a smart drug system with multiple stimulus responses to adapt to the complex process. Inspired by the cobweb, this study designs a microreticular nanosystem that adheres to tissue and is sequentially responsive to multiple stimuli in the ischaemic microenvironment. The nanosystem is fabricated from hyaluronic acid (HA), ROS‐responsive B‐PDEA, and hypoxia‐sensitive VEGF‐expressing plasmids (EPODNA) through electrostatic interactions. After intramyocardial injection, the tissue‐adhesive property of the nanosystem will significantly decrease its acute loss from the injection site. Extracellularly, the microreticular nanosystem first responds to activated hyaluronidase (hyal), releasing HA for microenvironment regulation and B‐PDEA/DNA nanoparticles (NP) with high transfection efficiency for cardiac cells. Intracellularly, ROS sequentially induced B‐PDEA/DNA NP dissociation, consuming some ROS to attenuate oxidative stress and releasing DNA to promote its expression. Meanwhile, local hypoxia significantly activates VEGF expression in plasmids for myocardial revascularization and repair. The function of the microreticular nanosystem is systematically evaluated in vitro. In a rat model of myocardial infarction, treatment with the microreticular nanosystem significantly promotes functional and structural improvements. Collectively, the study provides a promising smart nanosystem to promote tissue repair after complex damage.

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Section: Resultsmentioning

confidence: 99%

Cobweb‐Inspired Microenvironment‐Targeting Nanosystem with Sequential Multiple‐Stage Stimulus‐Response Capacity for Ischaemic Tissue Repair

Ding

Xing

Liu

et al. 2023

Adv Funct Materials

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“…Targeting brain (particularly motor cortical) microvascular health preventively and therapeutically might represent a powerful approach to mitigate ALS-related neurodegeneration. The link between vascular health, cerebromicrovascular integrity and synaptic or neuronal dysfunction in similar region-specific spreading neurodegenerative diseases, such as AD or PD, further highlights the importance of “(micro)vascular integration in neurodegeneration”, to go beyond a pure “neuron-centric” concept [ 74 , 165 ]. A spotlight on the relationship between microvascular and neuronal health is needed in ALS.…”

Section: Concluding Remarks On Vascular Rethinking In Als Managementmentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

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Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

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Section: Introductionmentioning

confidence: 99%

“…Emerging tissue engineering focuses on manufacturing medical biomaterials as new interventions to treat stroke lesions ( Gallego et al, 2022 ). Biomaterial-based therapy could transplant therapeutic stem cells or molecules into the targeted brain area rather precisely and with minimal invasion for the treatment of IS ( Gallego et al, 2022 ). In this case, the implantation of biomaterials into the cavity could provide solid structures to attract repair cells or release therapeutic drugs, indicating a possibility for successful clinical translation.…”

Section: Introductionmentioning

confidence: 99%

Perspective insights into hydrogels and nanomaterials for ischemic stroke

Zhang

Yang

et al. 2023

Front. Cell. Neurosci.

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Ischemic stroke (IS) is a neurological disorder prevalent worldwide with a high disability and mortality rate. In the clinic setting, tissue plasminogen activator (tPA) and thrombectomy could restore blood flow of the occlusion region and improve the outcomes of IS patients; however, these therapies are restricted by a narrow time window. Although several preclinical trials have revealed the molecular and cellular mechanisms underlying infarct lesions, the translatability of most findings is unsatisfactory, which contributes to the emergence of new biomaterials, such as hydrogels and nanomaterials, for the treatment of IS. Biomaterials function as structural scaffolds or are combined with other compounds to release therapeutic drugs. Biomaterial-mediated drug delivery approaches could optimize the therapeutic effects based on their brain-targeting property, biocompatibility, and functionality. This review summarizes the advances in biomaterials in the last several years, aiming to discuss the therapeutic potential of new biomaterials from the bench to bedside. The promising prospects of new biomaterials indicate the possibility of an organic combination between materialogy and medicine, which is a novel field under exploration.

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Therapeutic Opportunities and Delivery Strategies for Brain Revascularization in Stroke, Neurodegeneration, and Aging

Cited by 15 publications

References 231 publications

Cobweb‐Inspired Microenvironment‐Targeting Nanosystem with Sequential Multiple‐Stage Stimulus‐Response Capacity for Ischaemic Tissue Repair

Cobweb‐Inspired Microenvironment‐Targeting Nanosystem with Sequential Multiple‐Stage Stimulus‐Response Capacity for Ischaemic Tissue Repair

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Perspective insights into hydrogels and nanomaterials for ischemic stroke

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