Augmentation of peripheral lymphocyte-derived cholinergic activity in patients with acute ischemic stroke

• Published in: BMC neurology Vol. 19; no. 1; pp. 236 - 9
• Main Authors: Yuan, Meng, Han, Bin, Xia, Yiping, Liu, Ye, Wang, Chunyang, Zhang, Chao
• Format: Journal Article
• Language: English
• Published: London BioMed Central 15.10.2019; BioMed Central Ltd; BMC
• Subjects: Acetylcholine; Acetylcholine - immunology; Acetylcholine - metabolism; Acetylcholinesterase; Acetyltransferase; Aged; Animal models; Brain infarction; Brain Ischemia - immunology; Brain Ischemia - metabolism; Brain research; Cerebral infarction; Cerebrovascular disease and stroke; Choline; Choline O-acetyltransferase; Chromatography; Drug therapy; Female; Hospitals; Humans; Infection; Infections; Inflammation; Intracellular; Ischemia; Ischemic stroke; Leukocytes (mononuclear); Liquid chromatography; Lymphocytes; Lymphocytes - immunology; Lymphocytes - metabolism; Male; Mass spectrometry; Mass spectroscopy; Medical research; Medicine; Medicine & Public Health; Middle Aged; Mortality; Nervous system; Neurochemistry; Neurology; Neurosurgery; Parasympathetic nervous system; Patient outcomes; Peripheral blood mononuclear cells; Pneumonia; Research Article; Risk factors; Scientific imaging; Spectroscopy; Stroke; Stroke patients; Studies; United States > US; Germany; Acetylcholine; Inflammation; Ischemic stroke
• ISSN: 1471-2377; 1471-2377
• DOI: 10.1186/s12883-019-1481-5

Background Brain ischemia activates the parasympathetic cholinergic pathway in animal models of human disease. However, it remains unknown whether activation of the cholinergic pathway impacts immune defenses and disease outcomes in patients with ischemic stroke. This study investigated a possible association between peripheral cholinergic activity, post-stroke infection, and mortality. Methods In this study, we enrolled 458 patients with acute ischemic stroke (< 24 h after onset), 320 patients with ischemic stroke on day 10, and 216 healthy subjects. Peripheral cholinergic activity, reflected by intracellular acetylcholine (ACh) content in human peripheral blood mononuclear cells (PBMCs), was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Expression of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was measured by quantitative real-time PCR and western blot. Regression analyses were used to assess associations between peripheral cholinergic function and clinical outcomes. Results Within 24 h after the onset of acute ischemic stroke, there was a rapid increase in peripheral cholinergic activity that correlated with brain infarction volume ( r  = 0.67, P  < 0.01). Specifically, lymphocyte-derived ACh levels were significantly higher in stroke patients with pneumonia (0.21 ± 0.02 ng/10 6 PBMC versus 0.15 ± 0.01 ng/10 6 PBMC, P  = 0.03). Of note, lymphocytic AChE catalytic activity was significantly lower in these patients. One-year mortality was significantly greater in patients with higher intracellular ACh levels within the first 24 h after acute stroke. Conclusions Lymphocytes produced increased amounts of ACh in patients with acute stroke, and pneumonia was a likely result. The association between this enhanced cholinergic activity and increased risk of pneumonia/mortality suggests that increased cholinergic activity may contribute to fatal post-stroke infection.