Downregulated FTO Promotes MicroRNA-155-mediated Inflammatory Response in Cerebral Ischemia/Reperfusion Injury.

This study aimed to elucidate the mechanism for alteration of m6A RNA modification in cerebral ischemia/reperfusion(I/R) injury and identify novel therapeutic targets. A rat cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) followed by reperfusion. Changes in m6A RNA modification were evaluated by colorimetric quantification. The expression of the m6A methyltransferases METTL3, METTL14, and WTAP, and the demethylases FTO and ALKBH5 were determined using qPCR and western blot analyses. FTO was overexpressed in brain tissues via intracerebroventricular injection of adenoviruses encoding FTO. The protective effect of FTO on m6A RNA modification and cerebral I/R injury was assessed. MeRIP assays were used to detect the impact of FTO overexpression on m6A modification of pri-miR-155; qPCR analysis was used to identify its maturation. Finally, the role of miR-155 overexpression in the protective effects of FTO on cerebral I/R injury was examined. m6A levels of total RNA were increased, and m6A methyltransferase FTO expression was decreased in post-I/R injury cerebral tissues. FTO overexpression reversed the increase in m6A RNA modification and attenuated cerebral I/R injury. Furthermore, FTO overexpression increased the m6A modification of pri-miR-155 and enhanced its maturation to form miR-155. Notably, miR-155 overexpression blunted FTO's protective effect against cerebral I/R injury. We propose that downregulation of FTO expression contributes to increased m6A RNA modification in cerebral I/R injury. FTO overexpression reverses increased total m6A RNA modification and exerts a protective effect against cerebral I/R injury via downregulating m6A modification of pri-miR-155 to inhibit its maturation process.

Low-dose cerebral CT perfusion imaging (CTPI) of senile dementia: diagnostic performance.

To evaluate the clinical value of low-dose cerebral CTPI in the diagnosis of senile dementia, as an attempt to develop a new imaging method to diagnose this disease and measure its severity. 95 patients of senile dementia (52 with Alzheimer's disease (AD), 43 with vascular dementia (VD)) and 30 healthy subjects (control group) were underwent low-dose cerebral CTPI examinations with multi-slices spiral CT. The CTPI images were analyzed using perfusion software. Derived perfusion parameters including cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TTP) were measured. Diagnostic value of perfusion parameters was evaluated by receiver-operating characteristic (ROC) curve. The CBV and CBF of both of frontal lobe, temporal lobe, hippocampus and basal ganglial area in the patients with senile dementia were much lower than those in the healthy group. And MTT and TTP of the areas above-mentioned in the senile dementia group were higher than those in the control group. There was statistically significant difference between them (p<0.05). The areas under ROC curves of perfusion parameters left temporal lobe MTT, left the basal ganglia MTT and left the hippocampus MTT to diagnose senile dementia were 0.959, 0.920, 0.916, and diagnostic accuracy rate is higher. The areas under ROC curve of the left frontal MTT, the left basal ganglia CBV were 0.867 and 0.819, diagnosis accuracy medium. The results showed that cerebral CTPI is valuable for the diagnosis of senile dementia.

Fifty percent reduced-dose cerebral CT perfusion imaging of Alzheimer's disease: regional blood flow abnormalities.

To evaluate the value of 50% reduced-dose cerebral computed tomography (CT)perfusion imaging (CTPI) to show the perfusion abnormalities in Alzheimer's disease (AD), as an attempt to develop a new imaging protocol with lower radiation dose to track the correlation of AD with regional blood flow abnormalities. A total of 52 patients with AD were assigned to the AD group and 28 healthy volunteers served as the control group. All participants were given a 50% reduced-dose cerebral CTPI (current was reduced from 160 to 80 mA) test by a multislice spiral CT scanner. Perfusion parameters of the bilateral frontal cortex, temporal cortex, hippocampus, and basal ganglia were measured, including the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). Both the CBV and CBF values of the measured regions were significantly higher in the healthy control group than in the AD group (P < .05), while the MTT and TTP values of these cerebral areas were significantly lower in the healthy control group than in the AD group (P < .05). Four perfusion parameters, namely the MTT of the left frontal cortex, right temporal cortex, right basal ganglia, and right hippocampus, had the greatest sensitivity and a striking correlation with the incidence of AD. The blood flow per unit of time in the regions of interest was significantly lower in the AD group, which provides new evidence for the existence of microcirculation disturbance and ischemia in AD. The 50% reduced-dose cerebral CTPI scan is valuable to show the regional perfusion abnormalities in the patients with AD.