The effects of let7i on cerebral edema and hemorrhagic transformation after thrombolysis by rt-PA

Thrombolysis by recombinant tissue plasminogen activator (rt-PA) damages the blood-brain barrier (BBB), causing cerebral edema and hemorrhagic transformation (HT). However, the mechanism behind this process is mostly unknown. Sprague-Dawley (SD) rats were randomly divided into six groups: sham (saline treatment), model (thrombus treatment), thrombolysis (thrombolysis by rt-PA), delayed thrombolysis, overexpressing let7i with thrombolysis, and overexpressing let7i with delayed thrombolysis. Evans blue (EB) staining and water measurement were used to assess BBB permeability. Infarct volume, hemorrhage levels, and neurological scores were evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining Garcia-Yebenes, and the revised five-point scale method, respectively. We found that let7i was downregulated in the thrombolysis group compared with the model group. Although the BBB permeability, infarct volume, hematoma volume, brain water content, and neurological scores were all elevated in the model group, the overexpressing let7i group exhibited reductions in hematoma volume brain water content, neurological scores, and improvement in BBB integrity compared with the corresponding thrombolysis and delayed thrombolysis groups, respectively. Moreover, overexpression of let7i reduced occludin expression at the protein level after thrombolysis by rt-PA, as demonstrated by qRT-PCR and western blot. These results demonstrated that let7i participated in cerebral edema and HT associated with BBB dysfunction after thrombolysis by rt-PA via the occludin signaling pathway.