Qiyue Wang,Tao Wang,Shengfei Yang,Hui Du,Bo Zhang,Sirui Cui,Daishun Ling,Fangyuan Li
Calcium ions (Ca 2+ ) play crucial roles as second messengers in living cells and are associated with the onset and development of chronic brain diseases, including epilepsy. Dynamic and real-time imaging of extracellular calcium levels ([Ca 2+ ] ex ) in the brain holds great potential for identifying disease foci. Magnetic resonance imaging (MRI) is a powerful non-invasive tool for Ca 2+ imaging with unlimited depth penetration. However, current available Ca 2+ MR sensors lack the sensitivity to monitor small [Ca 2+ ] ex alterations associated with chronic brain diseases in vivo. In this study, a highly sensitive Ca 2+ -dependent T2-T1 switchable magnetic nanosensor is reported, consisting of Ca 2+ -specific ligands engineered near-paramagnetic iron oxide nanoparticles. Surface ligand modifications can be adjusted to regulate the interaction energy between sensors and Ca 2+ , allowing for customizable response range and sensitivity to fulfill the in vivo imaging requirements. The optimized sensors enable non-invasive visualization of early-stage seizure focus in mice undergoing epilepsy.
Summary Mutations in microglia may cause brain disorders. Replacement of dysfunctional microglia by allogeneic wild-type microglia from bone marrow transplantation (Mr BMT) or peripheral blood can correct the gene deficiency at the brain-wide scale but cannot achieve precise replacement at specific brain regions. Here, we introduce a strategy with potential clinical relevance—microglia replacement by microglia transplantation (Mr MT), combining tamoxifen-induced ablation of Mr BMT cells and intracranial injection of microglia to mouse brain, to achieve region-sepcific microglia replacement. The original abbreviation of this microglia replacement strategy is mrMT. We hereby change the name to Mr MT. For complete details on the use and execution of this protocol, please refer to Xu et al. (2020) .
Hongru Wang,Zheng Wei,Yangyang Zhao,Shidong Wang,Lili Cao,Fan Wang,Kai Liu,Yanfei Sun
Early diagnosis and treatment are of great significance for hindering the progression of brain disease. The limited effects of available treatments and poor prognosis are currently the most pressing problems faced by clinicians and their patients. Therefore, developing new diagnosis and treatment programs for brain diseases is urgently needed. Near-infrared (NIR)-light-responsive, lanthanide-doped upconversion nanoparticles (UCNPs) provide great advantages both in diagnosis and therapy. Hence, we synthesised nanoparticles comprised of a UCNPs core with surface functionalization. UCNPs@Au was used for NIR fluorescence imaging in the brain and inhibiting the growth of mouse glioma 261 (GL261) cells depending on photothermal properties. In addition, a UCNPs core and a mesoporous silica layer as the outer shell with a tannic acid–Al3+ ions (TA–Al) complex as a “gatekeeper” were used for pH-triggered doxorubicin/small interfering ribonucleic acid delivery in vitro. Based on our preliminary results, we expect to develop more multifunctional nanoscale diagnostic and therapeutic agents based on UCNPs for the diagnosis and treatment of brain diseases, including Alzheimer's disease, Parkinson's disease, and brain tumours.
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