体内脑缺血

Cerebral ischemia

Cerebral ischemia is the most common cause of stroke, which is a leading cause of permanent disability in adults worldwide^1,2It occurs when blood vessels serving the brain become blocked or burst depriving it of sufficient oxygen and nutrients. Consequently, the affected area of the brain cannot work properly and the bodily functions it controls are impaired, giving rise to a variety of disabilities, such as reduced mobility and coordination and impaired speech.

尽管了解脑缺血的病理生理学方面的进步，但几乎没有治疗选择²。大多数治疗都集中在大脑受影响区域的再灌注中，以恢复对被剥夺细胞的氧气供应，并使正常功能能够尽快恢复。

Although several different mechanisms are involved in the pathogenesis of cerebral ischemia, the resultant inflammation of brain tissue is believed to be a key factor in determining the extent of irreversible brain damage and associated disability³。发现炎症标记水平的增加与脑缺血后的预后不良相关。炎症反应对脑缺血的分子基础知之甚少，但烟碱乙酰胆碱受体（NACHR）的作用已被指出。⁴。

烟碱乙酰胆碱受体

The ligand-gated nAChRs are ion channels that are widely expressed throughout the peripheral and central nervous systems. A subtype of this group of receptors known as α7 is present across a range of different brain cells, including cortical neurons, microglia and astrocytes, where it serves a vital role in the control of a wide variety of physiological responses such as attention, memory, and locomotion⁵。

The α7 receptors have been implicated in the development of schizophrenia, Alzheimer’s disease and traumatic brain injury. Furthermore, stimulation of α7 receptors appears to provide neuronal protection against ischemic damage and cerebral haemorrhage^6,7。

Further elucidation of the function of these receptors may thus help reduce cerebral inflammation and improve outcomes in patients with cerebral ischemia and brain diseases. To investigate the role of these receptors, it is necessary to study them体内, and sophisticated imaging techniques have now made this possible.

脑成像

Positron emission tomography (PET) imaging and magnetic resonance imaging (MRI) are powerful tools for visualizing the effects of neurological and neurodegenerative diseases体内。Since these imaging techniques do not interfere with the normal functioning of the body they can be repeated several times to assess effects over time.

Selective PET radiotracers specific for α7 receptors have allowed the distribution of these receptors to be visualized. Although such studies have highlighted the role of α7 nAChRs in brain disorders, the role of nAChRs in the neuroinflammatory response to cerebral ischemia had not been determined.

Role of nicotinic receptors in cerebral ischemia

为了纠正这种差距在乙酰胆的理解involvement in cerebral ischemia, changes in the expression of the α7 receptor were studied in a rat model after inducing cerebral ischemia in the brain by a 90-minute intraluminal occlusion of the middle cerebral artery⁸。

用α7NACHRS激动剂PHA或对照对患有脑缺血的大鼠进行治疗，并通过体内宠物imaging with [¹¹C]NS14492 as the radiotracer. MRI was conducted using a 7 Tesla horizontal bore Bruker BioSpec 70/30 MRI system to monitor permeability of the blood brain barrier. The effect of the modulation of α7 receptors on neuroinflammation was explored with a specific radioligand for the translocator protein ([¹⁸F]DPA-714) 7 days after cerebral ischaemia. Real-time polymerase chain reaction was used to evaluate changes in gene expression.

Increased expression of α7 receptors was observed in microglia and astrocytes after cerebral ischaemia. The role of α7 receptors in the neuroinflammatory response to cerebral ischemia was supported by the decrease of [¹⁸F] DPA-714在用PHA 568487治疗的缺血大鼠中结合。此外，与对照相比，使用PHA 568487处理的PHA 568487显着减少了脑梗塞体积和改善的神经系统结果。α7NACHR的激活对血脑屏障的渗透性没有影响⁸。

Taken together, these results suggest that the nicotinic α7 nAChRs play a key role in the inflammatory reaction and the leukocyte recruitment following cerebral ischemia in rats

希望在这项研究中获得的新信息支持α7NACHR参与脑缺血后的神经炎症发展，这可能有助于发展新型策略，以减少缺血性中风和治疗方法减少其他神经系统疾病的负担。

参考

_{1. Anuncibay-Soto B, et al. Neuroprotection by salubrinal treatment in global cerebral ischemia. Neural Regen Res 2016;11:1744‑1745.}

_{2. Donnan GA等。中风。柳叶刀。2008，371：1612‑1623。。}

_{3. Muir KW, et al. Inflammation and ischaemic stroke. Curr Opin Neurol. 2007;20:334‑342.}

_{4. de Jonge WJ and Ulloa L. The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. British Journal of Pharmacology 2007;151(7), 915–929.}

_{5. Neumann S等。中风后先天免疫和炎症：α7-Nicotinic激动剂的观点。国际分子科学杂志2015; 16（12），29029–29046。}

_{6. Shimohama S等。烟碱α7受体预防谷氨酸神经毒性和神经元缺血性损伤。Brain Research1998; 779：359–363。}

_{7. Hijioka M等。尼古丁在脑出血的小鼠模型中的治疗作用。药理学与实验治疗学杂志2011; 338（3）：741–749。}

_{8. Colás L, et al. In vivo imaging of A7 nicotinic receptors as a novel method to monitor neuroinflammation after cerebral ischemia. Glia 2018;1–14. Available这里。}