Hofmeijer Jeannette, Mulder Alex T B, Farinha Ana C, van Putten Michel J A M, le Feber Joost
Clinical Neurophysiology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands; Department of Neurology, Rijnstate Hospital, Arnhem, the Netherlands.
Biomedical Signals and Sytems, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, the Netherlands.
Brain Res. 2014 Apr 4;1557:180-9. doi: 10.1016/j.brainres.2014.02.027. Epub 2014 Feb 20.
Eighty percent of patients with chronic mild cerebral ischemia/hypoxia resulting from chronic heart failure or pulmonary disease have cognitive impairment. Overt structural neuronal damage is lacking and the precise cause of neuronal damage is unclear. As almost half of the cerebral energy consumption is used for synaptic transmission, and synaptic failure is the first abrupt consequence of acute complete anoxia, synaptic dysfunction is a candidate mechanism for the cognitive deterioration in chronic mild ischemia/hypoxia. Because measurement of synaptic functioning in patients is problematic, we use cultured networks of cortical neurons from new born rats, grown over a multi-electrode array, as a model system. These were exposed to partial hypoxia (partial oxygen pressure of 150Torr lowered to 40-50Torr) during 3 (n=14) or 6 (n=8) hours. Synaptic functioning was assessed before, during, and after hypoxia by assessment of spontaneous network activity, functional connectivity, and synaptically driven network responses to electrical stimulation. Action potential heights and shapes and non-synaptic stimulus responses were used as measures of individual neuronal integrity. During hypoxia of 3 and 6h, there was a statistically significant decrease of spontaneous network activity, functional connectivity, and synaptically driven network responses, whereas direct responses and action potentials remained unchanged. These changes were largely reversible. Our results indicate that in cultured neuronal networks, partial hypoxia during 3 or 6h causes isolated disturbances of synaptic connectivity.
因慢性心力衰竭或肺部疾病导致慢性轻度脑缺血/缺氧的患者中，80%存在认知障碍。缺乏明显的结构性神经元损伤，且神经元损伤的确切原因尚不清楚。由于几乎一半的脑能量消耗用于突触传递，而突触功能障碍是急性完全缺氧的首个突然后果，因此突触功能障碍是慢性轻度缺血/缺氧时认知功能恶化的一种可能机制。由于测量患者的突触功能存在问题，我们使用新生大鼠的皮质神经元培养网络（生长在多电极阵列上）作为模型系统。将这些网络在3小时（n = 14）或6小时（n = 8）内暴露于部分缺氧环境（氧分压从150托降至40 - 50托）。通过评估自发网络活动、功能连接性以及突触驱动的网络对电刺激的反应，在缺氧前、缺氧期间和缺氧后评估突触功能。动作电位的高度和形状以及非突触刺激反应被用作单个神经元完整性的指标。在3小时和6小时的缺氧过程中，自发网络活动、功能连接性以及突触驱动的网络反应在统计学上显著降低，而直接反应和动作电位保持不变。这些变化在很大程度上是可逆的。我们的结果表明，在培养的神经元网络中，3小时或6小时的部分缺氧会导致突触连接性的孤立性紊乱。
