慢性铅暴露致MCI微血管病变的多模态MRI研究

慢性铅暴露早期可引起轻度认知障碍（MCI），晚期与痴呆相关的多种神经退行性疾病密切相关，后果十分严重。因此，早期评估慢性铅暴露MCI至关重要，但缺乏有效手段。本课题组长期从事铅诱导脑功能异常的相关机制研究，前期证实：成年慢性铅暴露破坏微血管结构，血脑屏障通透性增加，铅蓄积于海马和皮质，抑制海马长时程增强，损害学习记忆功能，提示铅致微血管病变可能是脑功能损伤的起始因素；综合3D-ASL、QSM和BOLD-fMRI等多模态MRI技术，能反映微血管病变区域。基于此，本课题围绕利用多模态MRI观察脑微血管病变特征评估慢性铅暴露致MCI这一科学问题，拟通过神经行为、多模态MRI、神经电生理与光遗传学等技术，明确慢性铅暴露、MCI及CNS微血管病变的相关性，阐明微血管病变特定脑区神经元电活动与脑功能变化之间的关系，为铅诱导脑功能损伤机制研究提供新视角，为预防和延缓慢性铅暴露诱发的脑功能损伤提供新靶点。

Chronic lead exposure could induce mild cognitive impairment (MCI) at the early stage, and it is correlated to many dementias associated neurodegenerative diseases at the late stage. The chronic lead exposure leads to very serious consequences. Therefore it is crucial to diagnose chronic lead exposure caused MCI in advance. However, the current methods of diagnosing chronic lead exposure induced MCI are very limited. Our group sticks to the mechanism of brain dysfunction caused by lead induced microangiopathy. We have revealed that adult chronic lead exposure destroys microvascular structures, increasing permeability of Blood-Brain Barrier, causing lead to accumulate in the hippocampus and cortex, in return reducing the hippocampus-dependent learning and memory by impairing the hippocampal long-term potentiation (LTP). These results suggest that lead induced microangiopathy is the early leading mechanism underlying brain function impairment. Combining 3D-ASL, QSM and BOLD-fMRI can reflect the area of microangiopathy. Based on this, this study will focus on the scientific issue of assessment of MCI neurological injury induced by chronic lead exposure based on multimodal MRI features of microangiopathy. We intend to evaluate the correlation of chronic lead exposure, MCI and CNS microangiopathy with neuropsychological behavior assessment, multimodal MRI, electrophysiology and optogenetics, aiming to clarify the changes of neuronal electrical activity in specific brain areas of microangiopathy. We will also aim to provide new perspectives for the study of the mechanism for lead-induced brain function impairment and provide a new possible target for preventing and delaying brain function impairment caused by chronic lead exposure.