Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
Epilepsia. 2022 Oct;63(10):2650-2663. doi: 10.1111/epi.17371. Epub 2022 Aug 2.
In adult brain tissue, oxygen levels typically remain in the normoxic zone, but status epilepticus results in hyperoxia, whereas brief self-terminating seizures lead to postictal hypoxia. The dynamic changes in oxygen levels and the underlying mechanisms are unknown in juveniles with febrile seizures.
Eight-day-old female and male rat pups were implanted with an electrode and oxygen-sensing optode in the hippocampus and then received once daily injections of lipopolysaccharide for 4 days to induce an immune response. Local partial pressure of oxygen (pO ) and local field potentials were recorded before, during, and after a heat-induced febrile seizure. Separate groups of pups received injections of vehicle or drugs targeting cyclooxygenase (COX)-1, COX-2, L-type calcium channels (LTCCs), and cannabinoid receptor type 1 (CB1) and transient receptor potential vanilloid-1 (TRPV1) receptors prior to febrile seizure induction to determine pO mechanisms. Following febrile seizures, a subset of pups were raised to young adulthood and then tested for learning impairments using the novel object recognition task.
Febrile seizures resulted in predictable oxygen dynamics that were related to behavioral seizures and epileptiform activity. During a behavioral seizure, pO rapidly increased, rapidly decreased, and then returned to near baseline. When the behavioral seizure terminated, oxygen levels climbed into the hyperoxic zone during a time of prolonged epileptiform activity. When epileptiform activity terminated, oxygen levels slowly returned to baseline. A COX-1 antagonist prevented hyperoxia, whereas a COX-2 antagonist did not. An LTCC antagonist exacerbated hyperoxia. Boosting levels of an endocannabinoid also exacerbated hyperoxia, whereas blocking CB1 receptors and TRPV1 receptors reduced hyperoxia. Inhibiting TRPV1 receptors during a febrile seizure prevented learning deficits in young adult female rats.
Brain oxygenation during and following a febrile seizure has a distinct pattern and multiple mechanisms. Brain oxygen dynamics may be an important consideration in the development of treatments for febrile seizures.
在成人脑组织中，氧水平通常保持在正常氧区，但癫痫持续状态导致过度氧合，而短暂的自限性发作则导致发作后缺氧。在热性惊厥的青少年中，氧水平的动态变化及其潜在机制尚不清楚。
将 8 天大的雌性和雄性幼鼠植入海马体的电极和氧敏光导纤维，并每天接受一次脂多糖注射，共 4 天以诱导免疫反应。在热诱导热性惊厥之前、期间和之后记录局部氧分压（pO ）和局部场电位。在诱导热性惊厥之前，单独的幼鼠组接受环氧化酶（COX）-1、COX-2、L 型钙通道（LTCC）和大麻素受体 1（CB1）和瞬时受体电位香草酸 1（TRPV1）受体的药物或药物注射，以确定 pO 机制。热性惊厥后，将一部分幼鼠饲养至成年早期，然后使用新物体识别任务测试学习障碍。
热性惊厥导致可预测的氧动力学，与行为性惊厥和癫痫样活动有关。在行为性惊厥期间，pO 迅速增加，迅速降低，然后恢复到接近基线。当行为性惊厥终止时，在长时间的癫痫样活动期间，氧水平攀升到高氧区。当癫痫样活动终止时，氧水平缓慢恢复到基线。COX-1 拮抗剂可预防高氧血症，而 COX-2 拮抗剂则不能。LTCC 拮抗剂加剧了高氧血症。增加内源性大麻素的水平也加剧了高氧血症，而阻断 CB1 受体和 TRPV1 受体则降低了高氧血症。在热性惊厥期间抑制 TRPV1 受体可防止年轻成年雌性大鼠的学习缺陷。
热性惊厥期间和之后的脑氧合具有独特的模式和多种机制。脑氧动力学可能是治疗热性惊厥的重要考虑因素。
