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

backgroundBrain 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.

methodsIn 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.

resultsWithin 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

conclusionsLymphocytes 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.