Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke.

Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has recently been reported to regulate microglial functions and exert anti-inflammatory effects. The intermittent burst stimulation (iTBS) regimen in rTMS improves neuronal excitability. However, whether iTBS exerts its anti-inflammatory effects by stimulating neurons and thereby modulating microglial polarization remains unclear. Motor function was assessed after 1 week of rTMS (iTBS regimen) treatment in adult male mice with occlusion/reperfusion of the middle cerebral artery (MCAO/r) injury. We also investigated the molecular biological alterations associated with microglial polarization using a cell proliferation assay, multiplex cytokine bioassays, and immunofluorescence staining. iTBS regimen can improve balance and motor coordination function, increase spontaneous movement, and improve walking function in mice with early cerebral ischemia injury. Expression levels of IL-1ß, TNF-α, and IL-10 increased significantly in mice with MCAO injury. Especially, rTMS significantly increased the number of proliferating cells in the infarcted cortex. The fluorescence intensity of MAP2 in the peri-infarct area of MCAO injured mice was low, but the signal was broader. Compared with MCAO group, the fluorescence intensity of MAP2 in rTMS group was significantly increased. rTMS inhibited pro-inflammatory M1 activation (Iba1+/CD86+) and improved anti-inflammatory M2 activation (Iba1+/CD206+) in the peri-infarct zone, thus significantly changing the phenotypic ratio M1/M2. rTMS improves motor dysfunction and neuroinflammation after cerebral I/R injury in mice by regulating microglial polarization.

Cystatin C and asymptomatic coronary artery disease in patients with metabolic syndrome and normal glomerular filtration rate.

BACKGROUND: All of the components of metabolic syndrome (MetS) have been regarded as risk factors for coronary artery disease (CAD). Early detection of CAD in asymptomatic patients with MetS remains a challenge. Cystatin C,which has been proposed as a novel marker of renal dysfunction,is correlated with mortality in CAD, The purpose of the study was to evaluate whether cystatin C is a potential marker of asymptomatic CAD in MetS patients with normal kidney function. METHODS: A total of 211asymptomatic MetS patients without prior history of CAD patients were included in a cross-sectional study. Patients were divided into MetS with asymptomatic CAD (n=136) and MetS without CAD (n=75) groups according to coronary angiograph results. Serum cystatin C levels were measured using particle enhanced immunonephelometric assays. We first assessed whether there is an independent association of cystatin C with the presence and severity of asymptomatic CAD. Then, we investigated the association between cystatin C and other biochemical risk factors for atherosclerosis. RESULTS: Serum cystatin C levels in patients with asymptomatic CAD were significantly higher than those without CAD (P=0.004). A multiple logistic regression analysis demonstrated cystatin C was independently associated with the presence of asymptomatic CAD (OR=1.326, 95%CI: 1.086-1.619). On receiver operating characteristics (ROC) analysis, the area under the curve (AUC) was 0.622 (95% CI: 0543-0.701, P=0.003), and cystatin C showed a moderate predictive value. Furthermore, cystatin C was independently correlated with Gensini score (standardized ß=0.183, P=0.007), and serum cystatin C levels increased with the increasing of number of disease vessels (P=0.005). In a multiple stepwise regression analysis, uric acid (UA)(P<0.001), body mass index (BMI)(P=0.002), triglyceride(TG)(P=0.03), estimated glomerular filtration rate (eGFR)(P<0.001), and fibrinogen(P=0.001) were independently associated with cystatin C. CONCLUSIONS: Serum cystatin C in our study was significantly associated with the presence and severity of asymptomatic CAD in MetS patients with normal kidney function, suggesting that cystatin C is probably more than a marker of glomerular filtration rate.