Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke
| Autor: | Quan Jiang, Qingjiang Li, Daniel A. Lawrence, Michael Chopp, Polly Arniego, Zhenggang Zhang, Manuel Yepes, Timothy A. Coleman, Li Zhang |
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| Rok vydání: | 2002 |
| Předmět: |
Male
Pathology medicine.medical_specialty Serine Proteinase Inhibitors medicine.medical_treatment Ischemia Infarction Pharmacology Blood–brain barrier Fibrinolytic Agents Neuroserpin Physiology (medical) medicine Animals Rats Wistar Stroke Serpins Adjuvants Pharmaceutic Vascular disease business.industry Neuropeptides Infarction Middle Cerebral Artery Plasminogen Thrombolysis medicine.disease Magnetic Resonance Imaging Rats medicine.anatomical_structure Neuroprotective Agents nervous system Intracranial Embolism Blood-Brain Barrier Tissue Plasminogen Activator Cardiology and Cardiovascular Medicine business Plasminogen activator |
| Zdroj: | Circulation. 106(6) |
| ISSN: | 1524-4539 |
| Popis: | Background — After stroke, the thrombolytic effect of tissue-type plasminogen activator (tPA) in the intravascular space is beneficial, whereas its extravascular effect on ischemic neurons is deleterious. We tested the hypothesis that neuroserpin, a natural inhibitor of tPA, reduces tPA-induced neuronal toxicity and increases its therapeutic window for treatment of embolic stroke. Methods and Results — Rats were subjected to embolic middle cerebral artery occlusion (MCAO). Ischemic brains were treated with neuroserpin in combination with recombinant human tPA (n=7), tPA alone (n=7), or saline (n=9). Neuroserpin (20 μL of 16 μmol/L active neuroserpin) was intracisternally injected 3 hours and tPA (10 mg/kg) was intravenously administered 4 hours after ischemia. MRI measurements were performed to study blood brain barrier (BBB) leakage and ischemic lesion volume. Administration of tPA alone 4 hours after ischemia significantly ( P P Conclusions — Administration of neuroserpin after stroke is neuroprotective, seemingly because it blocks the extravascular effect of tPA, leading to subsequent decrease in stroke volume and widening of the therapeutic window for the thrombolytic effect of tPA. |
| Databáze: | OpenAIRE |
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