d'Anglemont de Tassigny Xavier, Sirerol-Piquer M Salomé, Gómez-Pinedo Ulises, Pardal Ricardo, Bonilla Sonia, Capilla-Gonzalez Vivian, López-López Ivette, De la Torre-Laviana Francisco Javier, García-Verdugo José Manuel, López-Barneo José
Medical Physiology and Biophysics Department, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain.
Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain; Network Center of Biomedical Research on Neurodegenerative Diseases (CIBERNED), Spain.
Hypoxia (Auckl). 2015 Jun 8;3:15-33. doi: 10.2147/HP.S78248. eCollection 2015.
Chronic hypoxemia, as evidenced in de-acclimatized high-altitude residents or in patients with chronic obstructive respiratory disorders, is a common medical condition that can produce serious neurological alterations. However, the pathogenesis of this phenomenon is unknown. We have found that adult rodents exposed for several days/weeks to hypoxia, with an arterial oxygen tension similar to that of chronically hypoxemic patients, manifest a partially irreversible structural disarrangement of the subventricular neurogenic niche (subventricular zone) characterized by displacement of neurons and myelinated axons, flattening of the ependymal cell layer, and thinning of capillary walls. Despite these abnormalities, the number of neuronal and oligodendrocyte progenitors, neuroblasts, and neurosphere-forming cells as well as the proliferative activity in subventricular zone was unchanged. These results suggest that neural stem cells and their undifferentiated progeny are resistant to hypoxia. However, in vivo and in vitro experiments indicate that severe chronic hypoxia decreases the survival of newly generated neurons and oligodendrocytes, with damage of myelin sheaths. These findings help explain the effects of hypoxia on adult neurogenesis and provide new perspectives on brain responsiveness to persistent hypoxemia.
在适应不良的高原居民或慢性阻塞性呼吸系统疾病患者中所表现出的慢性低氧血症，是一种常见的医学状况，可导致严重的神经改变。然而，这一现象的发病机制尚不清楚。我们发现，成年啮齿动物连续数天/数周暴露于低氧环境中，其动脉血氧张力与慢性低氧血症患者相似，表现出室下神经源性微环境（室下区）部分不可逆的结构紊乱，其特征为神经元和有髓轴突移位、室管膜细胞层扁平以及毛细血管壁变薄。尽管存在这些异常，但室下区神经元和少突胶质细胞前体细胞、神经母细胞以及神经球形成细胞的数量以及增殖活性并未改变。这些结果表明神经干细胞及其未分化的后代对低氧具有抗性。然而，体内和体外实验表明，严重的慢性低氧会降低新生成的神经元和少突胶质细胞的存活率，并损害髓鞘。这些发现有助于解释低氧对成体神经发生的影响，并为大脑对持续性低氧血症的反应提供新的视角。
