Evaluating the impact of spreading depolarisations, post stroke, in the awake brain using graphene-enabled nanotechnology.

中风是全世界成年人死亡和残疾的常见原因。缺血性中风是脑血管阻塞的结果，该血管向大脑某一区域供应血液，导致大脑血流量严重减少。出血性中风或脑出血是脑血管破裂的结果。这种向大脑提供能量(氧气和葡萄糖)所需的血液流量的减少，会导致脑细胞死亡和神经功能丧失。对大脑的主要损害发生得非常快，在中风发生后的最初几个小时内，但可以持续几天甚至几周。大脑中血液供应最少、脑细胞死亡最快的区域被称为“核心”区域。相比之下，核心周围的大脑区域血流量减少，但脑细胞功能不全，被称为“半暗带”。随着时间的推移，半影区中的脑细胞可能会死亡，这会扩大核心区域，对大脑造成更大的损害。半影区是大脑中可以挽救的区域，也是大多数中风疗法的主要靶点。已知的病理性大脑信号波称为扩散去极化(SDS)，是核心扩张的主要因素，因此会恶化中风结果。抑郁自发地发生在中风后的半影区，并传播到整个大脑灰质。当十二烷基硫酸钠在大脑中传播时，它们会使脑细胞去极化，并导致几乎完全的离子稳态失稳。十二烷基硫酸钠还会导致半影区的脑血流量进一步减少，该区域已经在经历血流量的减少。癫痫发作也可发生在中风后，其频率可能被低估，因为许多癫痫发作仍然是局灶性的，很少或根本没有行为表现。在进行研究以设计抑制抑郁的治疗策略时，一个关键问题是缺乏临床前的电生理技术，能够以高时空分辨率检测记录抑郁的下流脑信号(低于0.1赫兹)。Wykes实验室已经成功地与材料科学家合作，他们设计和制造了基于石墨烯的神经生理探针阵列，能够记录大脑大片区域的SD，展示了它们在研究完整大脑中的病理大脑信号方面的有效性。我们现在的目标是将这一尖端技术应用于中风的临床前研究，以更好地了解SD的启动机制及其在清醒大脑中参与恶化中风严重性的过程。此外，我们的目标是设计一种抑制抑郁和减少卒中核心扩张的治疗策略。这项工作将是这项技术走向成熟的关键的第一步，走向未来的临床翻译，我们预计它将极大地促进神经重症监护病房患者的管理。

Stroke is a frequent cause of death and disability in adults worldwide. Ischaemic stroke is the result of a blockage in a cerebral blood vessel that supplies blood to a region of the brain, inducing a severe reduction in cerebral blood flow. Haemorrhagic stroke, or brain bleed, is the result of a cerebral vessel rupturing. This decrease in blood flow, which is needed to provide energy (oxygen and glucose) to the brain, results in the death of brain cells and loss of neurological function. The main damage to the brain happens very quickly, in the first few hours from when the stroke happened but can continue for days or even weeks. The region of the brain which has the lowest blood supply, and where brain cells die the quickest, is called the 'core' region. In contrast brain regions surrounding the core, that have reduced blood flow but with partially functioning brain cells, is called the 'penumbra'. The brain cells in the penumbra may, over time, die which expands the core region and contributes to greater damage to the brain. The penumbra region is the area of the brain that can be saved and is the main target for most stroke therapies. Waves of pathological brain signals called spreading depolarisations (SDs) are known to be major contributors to core expansion, and hence worsen stroke outcome. SDs spontaneously occur in the penumbra region, post stroke, and propagate throughout brain grey matter. As SDs propagate through the brain they depolarise brain cells and result in almost complete ion homeostasis failure. SDs also induce additional reduction of cerebral blood flow in the penumbra region, a region that is already experiencing a reduction in blood flow. Seizures can also occur post-stroke and their frequency is likely underreported due to the fact that many remain focal with little or no behavioural manifestation. A key problem when conducting research to design therapeutic strategies to suppress SDs is the lack of pre-clinical electrophysiological technology capable of detecting infraslow brain signals (below 0.1 Hz), where SDs are recorded, at high spatiotemporal resolution. The Wykes lab has successfully collaborated with the material scientists who designed and fabricate arrays of graphene-based neurophysiological probes capable of recording SDs across large areas of brain, demonstrating their usefulness for studying pathological brain signals in intact brain. We now aim to bring this cutting-edge technology to pre-clinical stroke research to gain a better understanding of the mechanisms of SD initiation and their involvement in worsening stroke severity, in the awake brain. Furthermore, we aim to design a therapeutic strategy that suppresses SDs and reduces stroke core expansion. This work will be a crucial first step in the maturity of this technology towards future clinical translation where we anticipate that it will greatly facilitate management of patients in the neuro-intensive care units.