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p75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin

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dc.contributor.authorXiao, Q.X.
dc.contributor.authorXue, L.L.
dc.contributor.authorTan, Y.X.
dc.contributor.authorHuangfu, L.R.
dc.contributor.authorChen, L.
dc.contributor.authorZhai, C.Y.
dc.contributor.authorMa, R.F.
dc.contributor.authorAl Hawwas, M.
dc.contributor.authorZhou, H.S.
dc.contributor.authorWang, T.H.
dc.contributor.authorZhou, X.F.
dc.contributor.authorXiong, L.L.
dc.date.issued2024
dc.descriptionData source: Supplementary material, https://doi.org/10.1016/j.biopha.2024.117338
dc.description.abstractA recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 μM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 μg/3 μl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.
dc.identifier.citationBiomedicine & Pharmacotherapy, 2024; 179(117338):1-17
dc.identifier.doi10.1016/j.biopha.2024.117338
dc.identifier.issn0753-3322
dc.identifier.issn1950-6007
dc.identifier.orcidZhou, X.F. [0000-0002-8687-0175]
dc.identifier.urihttps://hdl.handle.net/11541.2/40217
dc.language.isoen
dc.publisherElsevier Masson
dc.relation.fundingZunyi Medical University 12345 Future Talent Training Program-Technology Elite ZYSE-2021–03
dc.relation.fundingGuizhou Provincial Higher Education Science and Technological Innovation Team [2023]072
dc.relation.fundingGuizhou Province Distinguished Young Scientific and Technological Talent Program YQK[2023]040
dc.relation.fundingNational Natural Science Foundation of China 82001604
dc.relation.fundingNational Natural Science Foundation of China 82060243
dc.relation.fundingZunyi Science and Technology Bureau [2021] 39
dc.rightsCopyright 2024 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC license (https://creativecommons.org/licenses/by-nc/4.0/)
dc.source.urihttps://doi.org/10.1016/j.biopha.2024.117338
dc.subjectglial polarization
dc.subjectneonatal hypoxic-ischemic encephalopathy
dc.subjectNestin
dc.subjectneuronal survival and regeneration
dc.subjectp75ECD-Fc
dc.subjectMicroglia
dc.subjectNeurons
dc.subjectAnimals
dc.subjectAnimals, Newborn
dc.subjectHumans
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectHypoxia-Ischemia, Brain
dc.subjectDisease Models, Animal
dc.subjectReceptors, Nerve Growth Factor
dc.subjectRecombinant Fusion Proteins
dc.subjectNeuroprotective Agents
dc.subjectApoptosis
dc.subjectCell Survival
dc.subjectImmunoglobulin Fc Fragments
dc.subjectMale
dc.titlep75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12292217390001831 13292217380001831 p75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin
ror.mmsid9916905329301831

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