Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

Applications of magnetic resonance cholangiopancreatography after fat meal in the preoperative evaluation of the biliary system of the donors for living liver transplantation / 中华器官移植杂志

Objective To evaluate the applications of magnetic resonance cholangiopancreatography (MRCP) after fat meal in the preoperative evaluation of biliary anatomy of living liver donors.Methods Fifty cases of the preoperative donors for living liver transplantation were included and all had the corresponding intraoperative cholangiography (IOC) information. The MRCP of the donors for living liver transplantation was performed before and after fat meal (two fried eggs). The visualization and diameter of the secondary bile duct were analyzed before and after the fat meal. The results of the biliary branching pattern by MRCP after fat meal were compared with the corresponding IOC results. The accuracy, sensitivity,specificity, positive predictive value and negative predictive value of MRCP after the fat meal in distinguishing normal and any type of variant biliary anatomy were calculated. Results In all cases,82% of the 50 cases in MRCP before the fat meal could meet the diagnosis needs of the preoperative evaluation,and 100% of the 50 cases in MRCP after the fat meal could meet the diagnosis needs. There was significant difference in the demonstration quality and diameter of the secondary bile duct in MRCP before and after the fat meal (P＜0. 05). MRCP showed accurate anatomy of the biliary system, using IOC as the reference standard, in 49(98%) subjects. The sensitivity, specificity, positive predictive value and negative predictive value of MRC in distinguishing normal and any type of variant biliary anatomy were 98%,94. 7%, 100%, 10% and 96. 9%,respectively. Conclusion The MRCP after fat meal can clearly demonstrate the secondary bile duct and perfectly meet the needs of the preoperative evaluation of the living liver transplantation. The MRCP after fat meal and routine MRCP should be considered complementary to one another in order to avoid complications in living liver transplantation donors.