Neurogenesis Is Reduced at 48 h in the Subventricular Zone Independent of Cell Death in a Piglet Model of Perinatal Hypoxia-Ischemia

Frontiers in Pediatrics

article

Daniel Alonso-Alconada¹  Pierre Gressens²  Xavier Golay³  Nicola J. Robertson⁴ 

[1] Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country;NeuroDiderot, Inserm, Université de Paris;Department of Brain Repair and Rehabilitation, Institute of Neurology, University College London;Institute for Women’s Health, University College London;Edinburgh Neuroscience, Centre for Clinical Brain Sciences, The University of Edinburgh

关键词: newborn;    neonatal brain;    hypoxia-ischemia;    neurogenesis;    subventricular zone;   

DOI  :  10.3389/fped.2022.793189

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Cellular and tissue damage triggered after hypoxia-ischemia (HI) can be generalized and affect the neurogenic niches present in the central nervous system. As neuroregeneration may be critical for optimizing functional recovery in neonatal encephalopathy, the goal of the present work was to investigate the neurogenic response to HI in the neurogenic niche of the subventricular zone (SVZ) in the neonatal piglet. A total of 13 large white male piglets aged <24 h were randomized into two groups: i) HI group ( n = 7), animals submitted to transient cerebral HI and resuscitation; and ii) Control group ( n = 6), non-HI animals. At 48 h, piglets were euthanized, and the SVZ and its surrounding regions, such as caudate and periventricular white matter, were analyzed for histology using hematoxylin-eosin staining and immunohistochemistry by evaluating the presence of cleaved caspase 3 and TUNEL positive cells, together with the cell proliferation/neurogenesis markers Ki67 (cell proliferation), GFAP (neural stem cells processes), Sox2 (neural stem/progenitor cells), and doublecortin (DCX, a marker of immature migrating neuroblasts). Hypoxic-ischemic piglets showed a decrease in cellularity in the SVZ independent of cell death, together with decreased length of neural stem cells processes, neuroblast chains area, DCX immunoreactivity, and lower number of Ki67 + and Ki67 + Sox2 + cells. These data suggest a reduction in both cell proliferation and neurogenesis in the SVZ of the neonatal piglet, which could in turn compromise the replacement of the lost neurons and the achievement of global repair.

【 授权许可】

CC BY