Department of Neurology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808, 1070, Brussels, Belgium.
Bio-, Electro- And Mechanical Systems (BEAMS), Université Libre de Bruxelles, Avenue F.D. Roosevelt 50 CP165/56, 1050, Brussels, Belgium.
Sci Rep. 2022 Jul 5;12(1):11336. doi: 10.1038/s41598-022-15426-w.
Non-convulsive seizures and status epilepticus are frequent and associated with increased mortality in septic patients. However, the mechanism through which seizures impact outcome in these patients is unclear. As previous studies yielded an alteration of neurovascular coupling (NVC) during sepsis, we hypothesized that non-convulsive seizures, might further impair NVC, leading to brain tissue hypoxia. We used a previously developed ovine model of sepsis. Animals were allocated to sham procedure or sepsis; septic animals were studied either during the hyperdynamic phase (sepsis group) or after septic shock occurrence (septic shock group). After allocation, seizures were induced by cortical application of penicillin. We recorded a greater seizure-induced increase in the EEG gamma power in the sepsis group than in sham. Using a neural mass model, we also found that the theoretical activity of the modeled inhibitory interneurons, thought to be important to reproduce gamma oscillations, were relatively greater in the sepsis group. However, the NVC was impaired in sepsis animals, despite a normal brain tissue oxygenation. In septic shock animals, it was not possible to induce seizures. Cortical activity declined in case of septic shock, but it did not differ between sham or sepsis animals. As the alteration in NVC preceded cortical activity reduction, we suggest that, during sepsis progression, the NVC inefficiency could be partially responsible for the alteration of brain function, which might prevent seizure occurrence during septic shock. Moreover, we showed that cardiac output decreased during seizures in sepsis animals instead of increasing as in shams. The alteration of the seizure-induced systemic hemodynamic variations in sepsis might further affect cerebrovascular response to neuronal activation. Our findings support the hypothesis that anomalies in the cerebral blood flow regulation may contribute to the sepsis-associated encephalopathy and that seizures might be dangerous in such a vulnerable setting.
非惊厥性发作和癫痫持续状态在脓毒症患者中很常见，且与死亡率增加有关。然而，目前尚不清楚发作如何影响这些患者的预后。由于之前的研究表明脓毒症期间存在神经血管耦联（NVC）的改变，我们假设非惊厥性发作可能进一步损害 NVC，导致脑组织缺氧。我们使用了之前开发的脓毒症羊模型。动物被分配到假手术或脓毒症组；脓毒症动物在高动力期（脓毒症组）或发生感染性休克后（感染性休克组）进行研究。分配后，通过皮质应用青霉素诱发发作。与假手术组相比，我们发现脓毒症组脑电图γ功率的发作诱导增加更大。使用神经质量模型，我们还发现，在脓毒症组中，被认为对产生γ振荡很重要的模拟抑制性中间神经元的理论活性相对更大。然而，尽管脑组织氧合正常，但脓毒症动物的 NVC 受损。在感染性休克动物中，无法诱发发作。感染性休克动物的皮质活动下降，但与假手术或脓毒症动物无差异。由于 NVC 的改变先于皮质活动的减少，我们认为，在脓毒症进展过程中，NVC 的效率低下可能是大脑功能改变的部分原因，这可能阻止感染性休克期间发作的发生。此外，我们发现脓毒症动物在发作期间心输出量下降，而不是像假手术组那样增加。脓毒症发作时全身血流动力学变化的改变可能进一步影响脑血管对神经元激活的反应。我们的发现支持这样一种假设，即大脑血液流动调节的异常可能导致与脓毒症相关的脑病，并且在这种脆弱的情况下，发作可能是危险的。
