Cytokine changes in the pathophysiology of poststroke depression
ABSTRACT Poststroke depression (PSD) is a frequent psychiatric sequela after stroke, and its influence is detrimental. However, the etiology of PSD is still not clear. Although many studies have indicated that immune dysregulation plays an important role in the pathophysiology of depression, it is still unknown if PSD involves the same mechanism. Thus, the current study objectives were to evaluate whether there were cytokine changes when patients with ischemic stroke suffered from PSD.
We included ischemic stroke patients without depression when the stroke occurred and followed them for 1 year. The Hamilton Depression Rating Scale score and cytokines were assessed at baseline and at the 1st, 3rd, 6th, 9th and 12th months after stroke.
One hundred four patients with ischemic stroke participated and completed the study, and 12 suffered from PSD during the 1-year study period. There were significant increases in the cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interferon-γ, and the ratios of IL-6/IL-10 and TNF-α/IL-10 were also elevated. Interleukin-1β was too low to show any difference.
Our study suggested that immune imbalance plays a possible role in the pathophysiology of PSD and that IL-6 and TNF-α are key cytokines.
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ABSTRACT: Stroke variably activates interleukin- (IL-) 17 expression, reduces regulatory T cells, and induces oxidative stress, which may support neurodegeneration. Ischemic stroke patients were screened for depressive symptoms (Center for Epidemiological Studies Depression (CES-D)) and cognitive status (Mini Mental State Examination). Proinflammatory cytokines (IL-17, IL-23, and interferon- [IFN-] γ), anti-inflammatory cytokine IL-10, and lipid hydroperoxide (LPH), a measure of oxidative stress, were assayed from fasting serum. Of 47 subjects (age 71.8 ± 14.4 years, 36% female), 19 had depressive symptoms (CES-D ≥ 16), which was associated with poorer cognitive status (F 1,46 = 8.44, P = 0.006). IL-17 concentrations did not differ between subjects with and without depressive symptoms (F 1,46 = 8.44, P = 0.572); however, IL-17 was associated with poorer cognitive status in subjects with depressive symptoms (F 1,46 = 9.29, P = 0.004). In those subjects with depressive symptoms, IL-17 was associated with higher LPH (ρ = 0.518, P = 0.023) and lower IL-10 (ρ = -0.484, P = 0.036), but not in those without. In conclusion, poststroke depressive symptoms may be associated with cognitive vulnerability to IL-17 related pathways, involving an imbalance between proinflammatory and anti-inflammatory activity and increased oxidative stress.BioMed Research International 06/2014; 2014:245210. DOI:10.1155/2014/245210 · 2.71 Impact Factor
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ABSTRACT: Background: Major depression is diagnosed in 18% of patients following myocardial infarction (MI), and the antidepressant fluoxetine is shown to effectively decrease depressive symptoms and improve coronary heart disease prognosis. We observed the effect of fluoxetine on cardiac electrophysiology in vivo in a rat model of post-MI depression and the potential mechanism. Methods and results: Eighty adult male Sprague Dawley rats (200–250 g) were randomly assigned to five groups: normal control (control group), MI (MI group), depression (depression group), post-MI depression (model group), and post-MI depression treated with intragastric administration of 10 mg/kg fluoxetine (fluoxetine group). MI was induced by left anterior descending coronary artery ligation. Depression was developed by 4-week chronic mild stress (CMS). Behavior measurement was done before and during the experiment. Electrophysiology study in vivo and Western blot analysis were carried on after 4 weeks of CMS. After 4 weeks of CMS, depression-like behaviors were observed in the MI, depression, and model groups, and chronic fluoxetine administration could significantly improve those behaviors (P<0.05 vs model group). Fluoxetine significantly increased the ventricular fibrillation threshold compared with the model group (20.20±9.32 V vs 14.67±1.85 V, P<0.05). Expression of Kv4.2 was significantly reduced by 29%±12%, 24%±6%, and 41%±15%, respectively, in the MI group, CMS group, and model group, which could be improved by fluoxetine (30%±9%). But fluoxetine showed no improvement on the MI-induced loss of Cx43. Conclusion: The susceptibility to ventricular arrhythmias was increased in depression and post-MI depression rats, and fluoxetine may reduce the incidence of ventricular arrhythmia in post-MI depression rats and thus improve the prognosis. This may be related in part to the upregulation of Kv4.2 by fluoxetine.Drug Design and Discovery 02/2015; 10(9):763-772. DOI:10.2147/DDDT.S75863
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ABSTRACT: Depression is a commonly occurring and persistent sequel of stroke affecting approximately 29% of patients. An immunological hypothesis has been put forward, and synthesis of kynurenine from tryptophan has been proposed to link inflammatory activity with neurotoxicity and neurotransmitter dysfunction. This study assessed the relationship between peripheral blood kynurenine and poststroke depressive symptoms.Neuropsychiatric Disease and Treatment 09/2014; 10:1827-35. DOI:10.2147/NDT.S65740 · 2.15 Impact Factor