Constructing a Transient Ischemia Attack Model Utilizing Flexible Spatial Targeting Photothrombosis with Real-Time Blood Flow Imaging Feedback

Abstract

Transient ischemic attack (TIA) is an early warning sign of stroke and death, necessitating suitable animal models due to the associated clinical diagnostic challenges. In this study, we developed a TIA model using flexible spatially targeted photothrombosis combined with real-time blood flow imaging feedback. By modulating the excitation light using wavefront technology, we precisely created a square light spot (50 × 250 µm), targeted at the distal middle cerebral artery (dMCA). The use of laser speckle contrast imaging (LSCI) provided real-time feedback on the ischemia, while the excitation light was ceased upon reaching complete occlusion. Our results demonstrated that the photothrombus formed in the dMCA and spontaneously recanalized within 10 min (416.8 ± 96.4 s), with no sensorimotor deficits or infarction 24 h post-TIA. During the acute phase, ischemic spreading depression occurred in the ipsilateral dorsal cortex, leading to more severe ischemia and collateral circulation establishment synchronized with the onset of dMCA narrowing. Post-reperfusion, the thrombi were primarily in the sensorimotor and visual cortex, disappearing within 24 h. The blood flow changes in the dMCA were more indicative of cortical ischemic conditions than diameter changes. Our method successfully establishes a photochemical TIA model based on the dMCA, allowing for the dynamic observation and control of thrombus formation and recanalization and enabling real-time monitoring of the impacts on cerebral blood flow during the acute phase of TIA.