Real-time whole-brain imaging of hemodynamics and oxygenation at micro-vessel resolution with ultrafast wide-field photoacoustic microscopy

High-speed high-resolution imaging of the whole-brain hemodynamics is critically important to facilitating neurovascular research.High imaging speed and image quality are crucial to visualizing real-time hemodynamics in complex brain vascular networks,and tracking fast pathophysiological activities at the microvessel level,which will enable advances in current queries in neurovascular and brain metabolism research,including stroke,dementia,and acute brain injury.Further,real-time imaging of oxygen saturation of hemoglobin(sO_(2))can capture fast-paced oxygen delivery dynamics,which is needed to solve pertinent questions in these fields and beyond.Here,we present a novel ultrafast functional photoacoustic microscopy(UFF-PAM)to image the whole-brain hemodynamics and oxygenation.UFF-PAM takes advantage of several key engineering innovations,including stimulated Raman scattering(SRS)based dual-wavelength laser excitation,water-immersible 12-facet-polygon scanner,high-sensitivity ultrasound transducer,and deep-learning-based image upsampling.A volumetric imaging rate of 2 Hz has been achieved over a field of view(FOV)of 11×7.5×1.5 mm^(3) with a high spatial resolution of~10 μm.Using the UFF-PAM system,we have demonstrated proof-of-concept studies on the mouse brains in response to systemic hypoxia,sodium nitroprusside,and stroke.We observed the mouse brain's fast morphological and functional changes over the entire cortex,including vasoconstriction,vasodilation,and deoxygenation.More interestingly,for the first time,with the whole-brain FOV and micro-vessel resolution,we captured the vasoconstriction and hypoxia simultaneously in the spreading depolarization(SD)wave.We expect the new imaging technology will provide a great potential for fundamental brain research under various pathological and physiological conditions.

Targeting the SUMO pathway for neuroprotection in brain ischaemia

Small ubiquitin-like modifier(SUMO)conjugation(SUMOylation)is a post-translational protein modification that modulates almost all major cellular processes,and has been implicated in many human diseases.A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins(global SUMOylation)protects cells against ischaemia-induced damage,while suppressing global SUMOylation promotes cell injury after ischaemia.Indeed,SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia,including global brain ischaemia and focal brain ischaemia(ischaemic stroke).Here,we summarise findings on the role of SUMOylation in human diseases,brain ischaemia in particular,and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.