Thrombolysis with rhPro-UK 3 to 6 hours after embolic stroke in rat

• Published in: Neurological research (New York) 2019-11, Vol.41 (11), p.1034-1042
• Main Authors: Hao, Chun-Hua, Ding, Wen-Xia, Sun, Qian, Li, Xin-Xin, Wang, Wei-Ting, Zhao, Zhuan-You, Tang, Li-Da
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - pathology; Disease Models, Animal; embolic stroke; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Intracranial Embolism - complications; Intracranial Embolism - drug therapy; Male; rat; Rats, Sprague-Dawley; RhPro-UK; Stroke - complications; Stroke - drug therapy; therapeutic time window; Thromboembolism - complications; Thromboembolism - drug therapy; Thrombolysis; Thrombolytic Therapy - methods; Time Factors; Tissue Plasminogen Activator - pharmacology
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2019.1672388

Objectives: To investigate the thrombolysis with recombinant human prourokinase (rhPro-UK) on thromboembolic stroke in rats at different therapeutic time windows (TTW). Methods: Rats were subjected to embolic middle cerebral artery occlusion. RhPro-UK and positive control drugs rt-PA,UK were administered 3 h, 4.5 h, 6 h after inducing thromboem-bolic stroke. Neurological deficit scoring (NDS) was evaluated at 6 h and 24 h after the treatment. The lesion volume in cerebral hemispheres was measured by MRI scanning machine after 6 h of thrombolysis, and the infarct volume was measured by TTC stain, together with hemorrhagic volume quantified by a spectrophotometric assay after 24 h of thrombolysis. Results: RhPro-UK 10, 20 × 10 4  U/kg significantly improved the NDS after cerebral thromboembolism in rats at 3 h, 4.5 h TTW, and at the 6 h TTW, the NDS was improved by 28.0% (P = 0.0690) and 29.2% (P = 0.0927) at 6 h and 24 h after rhPro-UK 20 ×10 4  U/kg administration, respectively. RhPro-UK 10, 20 × 10 4  U/kg significantly reduced the brain lesions measured by MRI at 3 h and 4.5 h TTW. RhPro-UK 10, 20 × 10 4  U/kg significantly reduced the cerebral infarction measured by TTC at 3 h, 4.5 h TTW. There was no increase in cerebral hemorrhage compared with untreated group after rhPro-UK administration. Conclusions: RhPro-UK had an obvious therapeutic effect on ischemic stroke caused by thrombosis, and could be started within 4.5 h TTW with less side effects of cerebral hemorrhage than that of UK.