Receptor-associated protein promotes t-PA expression, reduces PAI-1 expression and improves neurorecovery after acute ischemic stroke

Receptor-associated protein (RAP) is a receptor antagonist that inhibits ligand interactions with the receptors that belong to the low density lipoprotein receptor gene family. The low-density lipoprotein receptor-related protein 1 (LRP1) has a crucial role in regulating tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression. Furthermore, the functional balance of these two proteins is directly associated with the initiation and development of cerebral ischemic stroke. In the present study, the effect of RAP post-treatment was investigated in a rat autologous thromboembolic model. The expression and activity of t-PA and PAI-1 were detected and the neurological function was tested. The results suggest that post-treatment with RAP is able to improve neurorecovery after ischemic stroke by decreasing vascular damage and regulating t-PA and PAI-1 expressions. Post-treatment with RAP promotes t-PA expression, suppresses PAI-1 expression, significantly improves functional outcomes and decreases the amount of TUNEL-positive cells. RAP-treated rats show lower intracranial hemoglobin levels and a smaller ischemic zone. In conclusion, post-treatment with RAP regulates t-PA and PAI-1 expressions and thereby contributes to the improvement of functional outcomes after cerebral ischemia. Our findings strongly suggest that RAP may be of value in neurorecovery after stroke.