{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:12:09Z","timestamp":1792181529612,"version":"4.4.0"},"reference-count":127,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>BACKGROUND: Cerebral circulation delivers the blood flow to the brain through a dedicated network of sanguine vessels. A healthy human brain can regulate cerebral blood flow (CBF) according to any physiological or pathological challenges. The brain is protected by its self-regulatory mechanisms, which are dependent on neuronal and support cellular populations, including endothelial ones, as well as metabolic, and even myogenic factors. OBJECTIVES: Accumulating data suggest that \u201cnon-pharmacological\u201d approaches might provide new opportunities for stroke therapy, such as electro-\/acupuncture, hyperbaric oxygen therapy, hypothermia\/cooling, photobiomodulation, therapeutic gases, transcranial direct current stimulations, or transcranial magnetic stimulations. We reviewed the recent data on the mechanisms and clinical implications of these non-pharmaceutical treatments. METHODS: To present the state-of-the-art for currently available non-invasive, non-pharmacological-related interventions in acute ischemic stroke, we accomplished this synthetic and systematic literature review based on the Preferred Reporting Items for Systematic Principles Reviews and Meta-Analyses (PRISMA). RESULTS: The initial number of obtained articles was 313. After fulfilling the five steps in the filtering\/selection methodology, 54 fully eligible papers were selected for synthetic review. We enhanced our documentation with other bibliographic resources connected to our subject, identified in the literature within a non-standardized search, to fill the knowledge gaps. Fifteen clinical trials were also identified. DISCUSSION: Non-invasive, non-pharmacological therapeutic\/rehabilitative interventions for acute ischemic stroke are mainly holistic therapies. Therefore, most of them are not yet routinely used in clinical practice, despite some possible beneficial effects, which have yet to be supplementarily proven in more related studies. Moreover, few of the identified clinical trials are already completed and most do not have final results. CONCLUSIONS: This review synthesizes the current findings on acute ischemic stroke therapeutic\/rehabilitative interventions, described as non-invasive and non-pharmacological.<\/jats:p>","DOI":"10.3390\/ijms23020907","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T12:34:04Z","timestamp":1642163644000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["Cellular and Molecular Targets for Non-Invasive, Non-Pharmacological Therapeutic\/Rehabilitative Interventions in Acute Ischemic Stroke"],"prefix":"10.3390","volume":"23","author":[{"given":"Gelu","family":"Onose","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelian","family":"Anghelescu","sequence":"additional","affiliation":[{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"},{"name":"Faculty of Midwives and Nursing, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Blendea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University \u201dTitu Maiorescu\u201d, 0400511 Bucharest, Romania"},{"name":"Physical and Rehabilitation Medicine & Balneology Clinic Division, Teaching Emergency Hospital of the Ilfov County, 022113 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlad","family":"Ciobanu","sequence":"additional","affiliation":[{"name":"Computer Science Department, Politehnica University of Bucharest, 060042 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Daia","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florentina","family":"Firan","sequence":"additional","affiliation":[{"name":"Physical and Rehabilitation Medicine & Balneology Clinic Division, Teaching Emergency Hospital of the Ilfov County, 022113 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihaela","family":"Oprea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aura","family":"Spinu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"},{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Popescu","sequence":"additional","affiliation":[{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anca","family":"Ionescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4678-9655","authenticated-orcid":false,"given":"\u0218tefan","family":"Busnatu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Medicine and Pharmacy \u201cCarol Davila\u201d, 020022 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-7710","authenticated-orcid":false,"given":"Constantin","family":"Munteanu","sequence":"additional","affiliation":[{"name":"Neuromuscular Rehabilitation Clinic Division, Teaching Emergency Hospital\u201d Bagdasar-Arseni\u201d, 041915 Bucharest, Romania"},{"name":"Faculty of Medical Bioengineering, University of Medicine and Pharmacy\u201d Grigore T. Popa\u201d, 700115 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3389\/fnins.2020.00473","article-title":"Application of Stem Cells in Stroke: A Multifactorial Approach","volume":"14","author":"Singh","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Mestre, H., Cohen-Minian, Y., Zajarias-Fainsod, D., and Ibarra, D.Z.-F.A.A. (2013). Pharmacological Treatment of Acute Ischemic Stroke. Neurodegener. Dis., 581\u2013614.","DOI":"10.5772\/53774"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1177\/1545968315604400","article-title":"The Specific Requirements of Neural Repair Trials for Stroke","volume":"30","author":"Dobkin","year":"2015","journal-title":"Neurorehabilit. 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