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

使用石墨烯纳米技术评估中风后清醒大脑中扩散去极化的影响。

• 批准号: MR/Y014545/1
• 负责人: Robert Wykes
• 金额: $ 140.8万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY014545%2F1
• 关键词: Evaluating; impact; spreading; depolarisations; post

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.

中风是全世界成人的经常导致死亡和残疾的原因。缺血性中风是脑血管阻塞的结果，该脑血管向大脑的一个区域提供血液，从而导致大脑血流严重降低。出血性中风或大脑出血，是脑血管破裂的结果。血液流量减少，这是为大脑提供能量（氧和葡萄糖）所需的，导致脑细胞死亡和神经功能的丧失。大脑的主要损害很快就会发生，从中风发生后的头几个小时，但可以持续数天甚至数周。大脑的血液供应最低，脑细胞死亡最快的区域称为“核心”区域。相比之下，核心周围的大脑区域减少了血液流动但有部分功能的脑细胞，称为“ Penumbra”。随着时间的流逝，半阴茎中的脑细胞可能会扩大核心区域并造成更大的损害对大脑的损害。半月形区域是可以保存的大脑区域，是大多数中风疗法的主要目标。称为扩散去极化（SD）的病理大脑信号波是核心扩张的主要因素，因此中风结果恶化。 SDS自发发生在半身区域，中风后，并在整个脑灰质中传播。随着SDS通过大脑传播时，它们会使脑细胞去极化，并导致几乎完整的离子稳态衰竭。 SDS还引起了阴前区域的脑血流的额外减少，该区域已经正在降低血流。中风后也可能发生癫痫发作，并且由于许多行为表现形式几乎没有或没有行为表现，因此其频率可能被低估了。进行研究以设计治疗策略以抑制SDS的一个关键问题是缺乏能够检测Infraslow脑信号（低于0.1 Hz）的临床前电生理技术，在高时空分辨率下记录了SDS。 Wykes Lab已与设计和制造基于石墨烯的神经生理探针的物质科学家成功合作，能够在大脑的大面积上记录SD，这表明它们可用于研究完整大脑中的病理脑信号。现在，我们旨在将这项尖端的技术带入临床前中风研究，以更好地了解SD启动的机制及其参与中风严重性的严重性。此外，我们旨在设计一种抑制SD并减少中风核心扩展的治疗策略。这项工作将是这项技术成熟到未来临床翻译的至关重要的第一步，我们预计这将极大地促进神经密集型护理部门中患者的管理。