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p75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin.
Xiao, Qiu-Xia; Xue, Lu-Lu; Tan, Ya-Xin; Huangfu, Li-Ren; Chen, Li; Zhai, Chen-Yang; Ma, Rui-Fang; Al-Hawwas, Mohammed; Zhou, Hong-Su; Wang, Ting-Hua; Zhou, Xin-Fu; Xiong, Liu-Lin.
Afiliación
  • Xiao QX; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China.
  • Xue LL; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China.
  • Tan YX; Animal Zoology Department, Institute of Neuroscience, Kunming Medical University, Yunnan, China; Department of Pediatrics, The PLA Rocket Force Characteristic Medical Center, Beijing, China.
  • Huangfu LR; Animal Zoology Department, Institute of Neuroscience, Kunming Medical University, Yunnan, China.
  • Chen L; Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Sichuan, China.
  • Zhai CY; Animal Zoology Department, Institute of Neuroscience, Kunming Medical University, Yunnan, China.
  • Ma RF; Animal Zoology Department, Institute of Neuroscience, Kunming Medical University, Yunnan, China.
  • Al-Hawwas M; Clinical and Health Sciences, University of South Australia, South Australia, Australia.
  • Zhou HS; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China.
  • Wang TH; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China. Electronic address: Wangth_email@163.com.
  • Zhou XF; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China. Electronic address: xin-fu.zhou@unisa.edu.au.
  • Xiong LL; Department of Anesthesiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Guizhou, China. Electronic address: 499465010@qq.com.
Biomed Pharmacother ; 179: 117338, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39278187
ABSTRACT
A 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos Fc de Inmunoglobulinas / Ratas Sprague-Dawley / Apoptosis / Hipoxia-Isquemia Encefálica / Nestina / Animales Recién Nacidos Límite: Animals / Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos Fc de Inmunoglobulinas / Ratas Sprague-Dawley / Apoptosis / Hipoxia-Isquemia Encefálica / Nestina / Animales Recién Nacidos Límite: Animals / Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Francia