Functional hyperconnectivity related to brain disease:maladaptive process or element of resilience?

Neuroimaging techniques such as magnetic resonance imaging(MRI)and positron emission tomography provide unique in vivo data to analyze structural and functional connectivity of the whole brain.Recent advances in small animal neuroimaging have opened new opportunities for the study of structure-function interactions in healthy and diseased brain networks,which are essential to develop therapies targeting network reorganization associated with functional improvement.

Structural integrity and remodeling underlying functional recovery after stroke

Stroke is the second leading cause of death worldwide with about 50% of survivors being chronically disabled(Donkor,2018).The behavioral improvement seen in stroke patients in the first weeks after a stroke is contributed by behavioral compensation, reorganization in somatotopic maps and activity in peri-infarct but also distant regions which are connected to the stroke area as supported by animal studies.

In vivo bioluminescence imaging to elucidate stem cell graft differentiation

Neurological disorders including neurodegeneration(e.g.,Alzheimer’s disease and Parkinson’s disease)and acute injuries(e.g.,stroke and traumatic brain injury)are the leading cause group of disability-adjusted life years and the second leading cause group of deaths.Different to other tissues,the adult brain retains only a very limited repair potential.Adult neurogenesis,the lifelong generation of new neurons,declines with age and in degenerative diseases,such as Alzheimer’s disease.Nevertheless,independently of age,the proliferation and migration of endogenous stem cells is stimulated after brain injuries and might be related to recovery processes(Adamczak et al.,2017).The limited number of endogenous stem cells during adulthood is one of the major limitations for an efficient regeneration of the injury affected brain regions.Therefore,the transplantation of neural stem or progenitor cells(NSCs/NPCs)is extensively studied in mouse models and applied in first clinical trials with the aim to replace dysfunctional or lost neural cells and thus to restore brain function.

Targeted nanoparticles for the non-invasive detection of traumatic brain injury by optical imaging and fluorine magnetic resonance imaging

Necrosis is a form of cell death that occurs only under pathological conditions such as ischemic diseases and traumatic brain injury （TBI）. Non-invasive imaging of the affected tissue is a key component of novel therapeutic interventions and measurement of treatment responses in patients. Here, we report a bimodal approach for the detection and monitoring of TBI. PEGylated poly（lactic-coglycolic acid） （PLGA） nanoparticles （NPs）, encapsulating both near infrared （NIR） fluorophores and perfluorocarbons （PFCs）, were targeted to necrotic ceils. We used cyanine dyes such as IRDye 800CW, for which we have previously demonstrated specific targeting to intracellular proteins of cells that have lost membrane integrity. Here, we show specific in vivo detection of necrosis by optical imaging and fluorine magnetic resonance imaging （^19F MRI） using newly designed PLGA NP（NIR700 ＋ PFC）-PEG-800CW. Quantitative ex vivo optical imaging and ^19F MR spectroscopy of NIR-PFC content in injured brain regions and in major organs were well correlated. Both modalities allowed the in vivo identification of necrotic brain lesions in a mouse model of TBI, with optical imaging being more sensitive than ^19F MRI. Our results confirm increased blood pool residence time of PLGA NPs coated with a PEG layer and the successful targeting of TBI-damaged tissue. A single PLGA NP containing NIR-PFC enables both rapid qualitative optical monitoring of the TBI state and quantitative 3D information from deeper tissues on the extent of the lesion by MRI. These necrosis-targeting PLGA NPs can potentially be used for clinical diagnosis of brain injuries.