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Arrays of reconnectable implantable fiber probes combined with advanced optogenetic fluorescent protein sensors are shown to enable a quantitative multisite time\u2010resolved study of oxidative\u2010stress and acidosis buildup dynamics as the key markers, correlates and possible drivers of ischemic stroke. The fiber probes designed for this work provide a wavelength\u2010multiplex forward\u2010propagation channel for a spatially localized, dual\u2010pathway excitation of genetically encoded fluorescence\u2010protein sensors along with a back\u2010propagation channel for the fluorescence return from optically driven fluorescence sensors. We show that the spectral analysis of the fiber\u2010probe\u2010collected fluorescence return provides means for a high\u2010fidelity autofluorescence background subtraction, thus enhancing the sensitivity of real\u2010time detection of stroke\u2010induced transients and significantly reducing measurement uncertainties in in vivo acute\u2010stroke studies as inherently statistical experiments operating with outcomes of multiply repeated measurements on large populations of individually variable animal stroke models.<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jbio202200050-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1002\/jbio.202200050","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T02:43:51Z","timestamp":1654224231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Real\u2010time fiber\u2010optic recording of acute\u2010ischemic\u2010stroke signatures"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-071X","authenticated-orcid":false,"given":"Matvey S.","family":"Pochechuev","sequence":"first","affiliation":[{"name":"Physics Department M.V. 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