Enduring neuroprotective effect of subacute neural stem cell transplantation after penetrating TBI

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dc.contributor.authorKassi, Anelia A. Y.
dc.contributor.authorMahavadi, Anil K.
dc.contributor.authorClavijo, Angelica
dc.contributor.authorCaliz, Daniela
dc.contributor.authorLee, Stephanie W.
dc.contributor.authorAhmed, Aminul I.
dc.contributor.authorYokobori, Shoji
dc.contributor.authorHu, Zhen
dc.contributor.authorSpurlock, Markus S.
dc.contributor.authorWasserman, Joseph M.
dc.contributor.authorRivera, Karla N.
dc.contributor.authorNodal, Samuel
dc.contributor.authorPowell, Henry R.
dc.contributor.authorDi, Long
dc.contributor.authorTorres, Rolando
dc.contributor.authorLeung, Lai Yee
dc.contributor.authorRubiano, Andrés M.
dc.contributor.authorBullock, Ross M.
dc.contributor.authorGajavelli, Shyam
dc.contributor.orcidRubiano, Andrés M. [0000-0001-8931-3254]
dc.date.accessioned2020-05-18T07:23:09Z
dc.date.available2020-05-18T07:23:09Z
dc.date.issued2019
dc.description.abstractenglishTraumatic brain injury (TBI) is the largest cause of death and disability of persons under 45 years old, worldwide. Independent of the distribution, outcomes such as disability are associated with huge societal costs. The heterogeneity of TBI and its complicated biological response have helped clarify the limitations of current pharmacological approaches to TBI management. Five decades of effort have made some strides in reducing TBI mortality but little progress has been made to mitigate TBI-induced disability. Lessons learned from the failure of numerous randomized clinical trials and the inability to scale up results from single center clinical trials with neuroprotective agents led to the formation of organizations such as the Neurological Emergencies Treatment Trials (NETT) Network, and international collaborative comparative effectiveness research (CER) to re-orient TBI clinical research. With initiatives such as TRACK-TBI, generating rich and comprehensive human datasets with demographic, clinical, genomic, proteomic, imaging, and detailed outcome data across multiple time points has become the focus of the field in the United States (US). In addition, government institutions such as the US Department of Defense are investing in groups such as Operation Brain Trauma Therapy (OBTT), a multicenter, pre-clinical drug-screening consortium to address the barriers in translation. The consensus from such efforts including "The Lancet Neurology Commission" and current literature is that unmitigated cell death processes, incomplete debris clearance, aberrant neurotoxic immune, and glia cell response induce progressive tissue loss and spatiotemporal magnification of primary TBI. Our analysis suggests that the focus of neuroprotection research needs to shift from protecting dying and injured neurons at acute time points to modulating the aberrant glial response in sub-acute and chronic time points. One unexpected agent with neuroprotective properties that shows promise is transplantation of neural stem cells. In this review we present (i) a short survey of TBI epidemiology and summary of current care, (ii) findings of past neuroprotective clinical trials and possible reasons for failure based upon insights from human and preclinical TBI pathophysiology studies, including our group's inflammation-centered approach, (iii) the unmet need of TBI and unproven treatments and lastly, (iv) present evidence to support the rationale for sub-acute neural stem cell therapy to mediate enduring neuroprotection.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.3389/fneur.2018.01097
dc.identifier.issn1664-2295
dc.identifier.urihttps://hdl.handle.net/20.500.12495/2910
dc.language.isoeng
dc.publisherFrontiers Mediaspa
dc.publisher.journalFrontiers in neurologyspa
dc.relation.ispartofseriesFrontiers in neurology, 1664-2295, Vol 9, 2019, pag 1-27spa
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fneur.2018.01097/full
dc.rightsAttribution 4.0 International*
dc.rights.creativecommons2019
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subject.decsLesiones traumáticas del encéfalospa
dc.subject.decsCélulas-madre neuralesspa
dc.subject.decsTrasplante de célulasspa
dc.subject.keywordsTraumatic brain injuryspa
dc.subject.keywordsInflammasomespa
dc.subject.keywordsPyroptosisspa
dc.subject.keywordsNeural stem cellspa
dc.subject.keywordsCell transplantationspa
dc.titleEnduring neuroprotective effect of subacute neural stem cell transplantation after penetrating TBIspa
dc.title.translatedEnduring neuroprotective effect of subacute neural stem cell transplantation after penetrating TBIspa
dc.typearticlespa
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localartículospa

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