Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows

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González-Nieto, Daniel and Fernández-Serra, Rocío and Pérez-Rigueiro, José and Panetsos Petrova, Fivos and Martinez-Murillo, Ricardo and Guinea, Gustavo V. (2020) Biomaterials to Neuroprotect the Stroke Brain: A Large Opportunity for Narrow Time Windows. Cells, 9 (5). p. 1074. ISSN 2073-4409

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Official URL: https://doi.org/10.3390/cells9051074




Abstract

Ischemic stroke represents one of the most prevalent pathologies in humans and is a leading cause of death and disability. Anti-thrombolytic therapy with tissue plasminogen activator (t-PA) and surgical thrombectomy are the primary treatments to recanalize occluded vessels and normalize the blood flow in ischemic and peri-ischemic regions. A large majority of stroke patients are refractory to treatment or are not eligible due to the narrow time window of therapeutic efficacy. In recent decades, we have significantly increased our knowledge of the molecular and cellular mechanisms that inexorably lead to progressive damage in infarcted and peri-lesional brain areas. As a result, promising neuroprotective targets have been identified and exploited in several stroke models. However, these considerable advances have been unsuccessful in clinical contexts. This lack of clinical translatability and the emerging use of biomaterials in different biomedical disciplines have contributed to developing a new class of biomaterial-based systems for the better control of drug delivery in cerebral disorders. These systems are based on specific polymer formulations structured in nanoparticles and hydrogels that can be administered through different routes and, in general, bring the concentrations of drugs to therapeutic levels for prolonged times. In this review, we first provide the general context of the molecular and cellular mechanisms impaired by cerebral ischemia, highlighting the role of excitotoxicity, inflammation, oxidative stress, and depolarization waves as the main pathways and targets to promote neuroprotection avoiding neuronal dysfunction. In the second part, we discuss the versatile role played by distinct biomaterials and formats to support the sustained administration of particular compounds to neuroprotect the cerebral tissue at risk of damage.


Item Type:Article
Uncontrolled Keywords:stroke; brain ischemia; inflammation; excitotoxicity; oxidative stress; spreading depression; neuroprotection; drug delivery; biomaterials; polymers; nanoparticles; hydrogels
Subjects:Medical sciences > Medicine > Neurosciences
ID Code:64384
Deposited On:18 Mar 2021 17:50
Last Modified:22 Mar 2021 08:03

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