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.
Highlights
Demographic change is an undeniable reality in modern countries
It is assumed that the modulation of activity in molecules related to inflammation/oxidative stress/excitotoxicity pathways produces neuroprotection during the window of intervention, the efficacy of such neuroprotective treatments is limited by a profound decay of activity linked with the poor stability and rapid degradation of majority of neuroprotective compounds
NPs have been conventionally classified as different types, including (1) polymeric NPs, (2) lipid-based NPs composed of fatty acids and triglycerides, (3) inorganic NPs formed by silicon, pure metals, and alloys, or (4) hybrid NPs
Summary
Daniel González-Nieto 1,2,3, *, Rocío Fernández-Serra 1,2 , José Pérez-Rigueiro 1,3,4 , Fivos Panetsos 5,6 , Ricardo Martinez-Murillo 7 and Gustavo V. Departamento de Tecnología Fotónica y Bioingeniería, ETSI Telecomunicaciones, Universidad Politécnica de Madrid, 28040 Madrid, Spain. Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine (CIBER-BBN), 28029 Madrid, Spain. Brain Plasticity Group, Health Research Institute of the Hospital Clínico San Carlos (IdISSC), Department of Translational Neuroscience, Instituto Cajal (CSIC), 28002 Madrid, Spain;
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