A fibrin targeted molecular imaging evaluation of microvascular no‐reflow in acute ischemic stroke

Abstract

Objective
To investigate the relationship between fibrin deposition and “no‐reflow” within microcirculation after thrombolysis in acute ischemic stroke (AIS).


Materials and methods
Experiments were approved by the institutional animal care and use committee. An experimental AIS model was induced in C57BL/6 mice by middle cerebral artery occlusion (MCAO) via the photothrombotic method. Mice were randomly assigned to non‐thrombolytic or thrombolytic treated groups (n = 12 per group). The modified Neurological Severity Score and Fast Beam Balance Test were performed by a researcher blinded to the treatment method. MRI was utilized to evaluate all of the mice. An FXIIIa‐targeted probe was applied to detect fibrin deposition in acute ischemic brain regions by fluorescence imaging. Necrosis and pathological changes of brain tissue were estimated via Hematoxylin and eosin staining while fibrin deposition was observed by immunohistochemistry.


Results

Thrombolytic therapy improved AIS clinical symptoms. The infarct area of non‐thrombolytic treated mice was significantly greater than that of the thrombolytic treated mice (
p
 < .0001). Fluorescent imaging indicated fibrin deposition in ischemic brain tissue in both groups, with less fibrin in non‐thrombolytic treated mice than thrombolytic treated mice, though the difference was not significant. Brain cells with abnormal morphology, necrosis, and liquefication were observed in the infarcted area for both groups. Clotted red blood cells (RBCs) and fibrin build‐up in capillaries were found near the ischemic area in both non‐thrombolytic and thrombolytic treated groups of mice.



Conclusion
Fibrin deposition and stacked RBCs contribute to microcirculation no‐reflow in AIS after thrombolytic therapy.