Progression of neuronal damage in an in vitro model of the ischemic penumbra

Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function. After ≈6 hours, activity and connectivity partially recovered, even during continuing hypoxia. If the oxygen supply was restored within 12 hours, changes in network connectivity were completely reversible. For longer periods of hypoxia (12–30 h), activity levels initially increased, but eventually decreased and connectivity changes became partially irreversible. After ≈30 hours, all functional connections disappeared and...

脑梗死周围缺血半暗带（ischemic penumbra）内神经元恢复的改善，对提升急性缺血性脑卒中患者的临床康复具有巨大潜力。然而，半暗带内驱动神经元恢复或继发性损伤的病理生理机制尚未完全阐明。我们采用缺血半暗带模型系统开展研究，该模型由暴露于可控水平与时长缺氧环境的体外培养皮层神经元网络构成。短时长缺氧（血氧分压pO2≈20mmHg）会因突触功能受损而降低神经元的自发放电活动。在缺氧约6小时后，即使仍处于持续缺氧环境中，神经元网络的活性与连接性已实现部分恢复。若在12小时内恢复血氧供应，则神经元网络连接的改变可完全逆转。对于12至30小时的长时长缺氧，神经元活性水平起初会升高，但最终会下降，且网络连接的改变将变得部分不可逆。缺氧约30小时后，所有功能性连接均消失且……