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Published on: November 12, 2013
Receptor-associated protein promotes t-PA expression, reduces PAI-1 expression and improves neurorecovery after acute
Dan-Dong Li1, Hong-Gang Pang1, Jin-Ning Song1
1Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Abstract:
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.
Insights
Receptor-associated protein (RAP) post-treatment improves neurorecovery after ischemic stroke. It regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression, reducing damage and enhancing functional outcomes.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Receptor-associated protein (RAP) antagonizes ligand interactions with low-density lipoprotein receptor gene family members.
- Low-density lipoprotein receptor-related protein 1 (LRP1) critically regulates tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression.
- The balance of t-PA and PAI-1 is vital in cerebral ischemic stroke development.
Purpose of the Study:
- To investigate the therapeutic effect of RAP post-treatment in a rat model of cerebral ischemic stroke.
- To evaluate the impact of RAP on t-PA and PAI-1 expression and activity.
- To assess RAP's influence on neurological function and brain tissue damage.
Main Methods:
- An autologous thromboembolic rat model of cerebral ischemia was utilized.
- Expression and activity of t-PA and PAI-1 were measured post-RAP treatment.
- Neurological function, vascular damage, and cell death (TUNEL assay) were assessed.
Main Results:
- Post-treatment with RAP significantly improved neurorecovery and functional outcomes.
- RAP administration promoted t-PA expression and suppressed PAI-1 expression.
- RAP treatment reduced vascular damage, intracranial hemoglobin levels, and the ischemic zone size.
Conclusions:
- Post-treatment with RAP effectively improves functional outcomes after cerebral ischemia.
- RAP's neuroprotective effects are mediated by regulating t-PA and PAI-1 expression.
- RAP shows potential as a therapeutic agent for stroke neurorecovery.
