Data from: 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 no activity remained. Since this complete silence seemed unrelated to hypoxic depths, but always followed an extended period of low activity, we speculate that irreversible damage (at least partly) results from insufficient neuronal activation. This opens avenues for therapies to improve recovery by neuronal activation.

脑梗死（brain infarct）周围缺血半暗带（ischemic penumbra）的神经功能恢复改善，对提升急性缺血性脑卒中（acute ischemic stroke）患者的临床转归具有巨大潜力。然而，半暗带内介导功能恢复或继发性损伤的病理生理机制尚未完全阐明。本研究以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所构成的半暗带模型系统为对象，探究其神经动态变化。短时缺氧（pO2≈20mmHg）因突触功能受阻，会降低神经元的自发性活动。在缺氧约6小时后，即使仍处于持续缺氧状态，神经元活动与网络连接性可部分恢复。若在12小时内恢复供氧，网络连接性的改变可完全逆转。对于时长更长的缺氧（12~30小时），神经元活动水平起初会升高，但最终会下降，且网络连接性的改变会变得部分不可逆。缺氧约30小时后，所有功能性连接均消失，神经元活动完全停止。由于这种完全静息状态似乎与缺氧程度无关，且始终出现在长时间低活动状态之后，我们推测不可逆损伤（至少部分）源于神经元激活不足。这为通过神经元激活改善功能恢复的治疗策略开辟了新路径。