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。缺血性中风是向大脑某个区域供血的脑血管堵塞的结果，导致脑血流量严重减少。出血性中风或脑出血是脑血管破裂的结果。为大脑提供能量（氧气和葡萄糖）所需的血流量减少，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，在中风发生的最初几个小时内，但可能持续几天甚至几周。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。相反，核心周围的脑区，血流量减少，但部分功能脑细胞，被称为“半影”。随着时间的推移，半影区的脑细胞可能会死亡，这会扩大核心区域，并对大脑造成更大的损害。半影区是大脑中可以保存的区域，也是大多数中风治疗的主要目标。被称为扩散去极化（SD）的病理性脑信号波是核心扩张的主要贡献者，因此恶化了卒中结局。SD自发地发生在中风后的半影区，并在整个大脑灰质中传播。当SD在大脑中传播时，它们使脑细胞去极化并导致几乎完全的离子稳态失败。SD还引起半影区脑血流量的额外减少，半影区是已经经历血流量减少的区域。癫痫发作也可能发生在中风后，其频率可能被低估，因为许多癫痫发作仍然是局灶性的，很少或没有行为表现。进行研究以设计治疗策略来抑制SD时的一个关键问题是缺乏能够以高时空分辨率检测记录SD的次声脑信号（低于0.1 Hz）的临床前电生理技术。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学探针阵列，能够记录大脑大面积的SD，证明了它们在研究完整大脑中的病理性大脑信号方面的有用性。我们现在的目标是将这种尖端技术应用于临床前中风研究，以更好地了解SD启动的机制及其在清醒大脑中参与中风严重程度恶化的机制。此外，我们的目标是设计一种治疗策略，抑制SD和减少中风核心扩展。这项工作将是这项技术成熟的关键第一步，我们预计它将大大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.