Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
Department of Cell Biology and Anatomy, University of Calgary, Calgary, Alberta, Canada.
J Neurophysiol. 2022 Sep 1;128(3):727-737. doi: 10.1152/jn.00533.2021. Epub 2022 Aug 17.
Repetitive mild traumatic brain injuries (RmTBIs) are increasingly recognized to have long-term neurological sequelae in a significant proportion of patients. Individuals that have had RmTBIs exhibit a variety of sensory, cognitive, or behavioral consequences that can negatively impact quality of life. Brain tissue oxygen levels ([Formula: see text]) are normally maintained through exquisite regulation of blood supply to stay within the normoxic zone (18-30 mmHg in the rat hippocampus). However, during neurological events in which brain tissue oxygen levels leave the normoxic zone, neuronal dysfunction and behavioral deficits have been observed, and are frequently related to poorer prognoses. The oxygenation response in the brain after RmTBIs/repeated concussions has been poorly characterized, with most preliminary research limited to the neocortex. Furthermore, the mechanisms by which RmTBIs impact changes to brain oxygenation and vice versa remain to be determined. In the current study, we demonstrate that upon receiving RmTBIs, rats exhibit posttraumatic, electrographic seizures in the hippocampus, without behavioral (clinical) seizures, that are accompanied by a long-lasting period of hyperoxygenation. These electrographic seizures and the ensuing hyperoxic episodes are associated with deficits in working memory and motor coordination that were reversible through attenuation of the posttraumatic and postictal (postseizure) hyperoxia, via administration of a vasoconstricting agent, the calcium channel agonist Bay K8644. We propose that the posttraumatic period characterized by brain oxygenation levels well above the normoxic zone, may be the basis for some of the common symptoms associated with RmTBIs. We monitor oxygenation and electrographic activity in the hippocampus, immediately before and after mild traumatic brain injury. We demonstrate that as the number of injuries increases from 1 to 3, the proportion of rats that exhibit electrographic seizures and hyperoxia increases. Moreover, the presence of electrographic seizures and hyperoxia are associated with postinjury behavioral impairments, and if the hyperoxia is blocked with Bay K8644, the behavioral deficits are eliminated.
重复性轻度创伤性脑损伤（RmTBIs）在很大一部分患者中被越来越多地认为具有长期的神经后遗症。有过 RmTBIs 的个体表现出各种感觉、认知或行为后果，这些后果可能会对生活质量产生负面影响。脑氧水平（[公式：见文本]）通常通过精细调节血液供应来维持在正常氧合区（大鼠海马体中的 18-30mmHg）。然而，在脑氧水平离开正常氧合区的神经事件中，已经观察到神经元功能障碍和行为缺陷，并且经常与预后较差有关。RmTBIs/反复脑震荡后大脑的氧合反应特征描述较差，大多数初步研究仅限于大脑皮层。此外，RmTBIs 如何影响脑氧合变化以及反之亦然的机制仍有待确定。在本研究中，我们证明在接受 RmTBIs 后，大鼠海马体出现创伤后、脑电图发作，没有行为（临床）发作，同时伴有长时间的高氧血症。这些脑电图发作和随之而来的高氧发作与工作记忆和运动协调的缺陷有关，通过使用血管收缩剂钙通道激动剂 Bay K8644 来减轻创伤后和发作后（发作后）高氧血症，这些缺陷是可逆的。我们提出，以脑氧水平远远高于正常氧合区为特征的创伤后时期，可能是与 RmTBIs 相关的一些常见症状的基础。我们监测海马体的氧合和脑电图活动，在轻度创伤性脑损伤之前和之后立即进行。我们证明，随着损伤次数从 1 次增加到 3 次，出现脑电图发作和高氧血症的大鼠比例增加。此外，脑电图发作和高氧血症的存在与损伤后的行为障碍有关，如果用 Bay K8644 阻断高氧血症，则行为缺陷消除。
