Department of Critical Care, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
J Neurosci. 2012 Apr 4;32(14):4972-81. doi: 10.1523/JNEUROSCI.5597-11.2012.
Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia-ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic reticular nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on postnatal day 17. We found that 48-72 h after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6-8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine minutes of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the reticular nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest.
全球缺氧缺血会中断整个大脑的氧气输送和血流。以前关于全脑缺氧缺血的研究主要集中在大脑皮层和海马体的损伤上。易受影响的神经元群体还包括丘脑网状核中的抑制性神经元。因此,我们研究了全脑缺氧缺血对年轻大鼠体感系统丘脑回路功能的影响。我们使用单细胞记录和控制胡须偏转来检查 17 天大的窒息性心脏骤停后大鼠幸存者对感觉刺激的丘脑皮质神经元的反应。我们发现,心脏骤停后 48-72 小时,丘脑皮质神经元在自发活动和对胡须偏转的反应中表现出明显升高的放电率。升高的诱发放电率在损伤后至少持续 6-8 周。尽管整体放电增加,但在 6 周时,丘脑皮质神经元表现出退化的感受野,对相邻的胡须反应减弱。9 分钟的窒息性心脏骤停与体感核中的神经突广泛退化以及网状核中的小胶质细胞激活有关。心脏骤停期间的全脑缺氧缺血对丘脑回路处理和感觉信息传递有长期影响。丘脑回路及其功能的正常化可能是心脏骤停后一个独特的治疗靶点。