Intracerebral Hirudin Injection Attenuates Ischemic Damage and Neurologic Deficits without Altering Local Cerebral Blood Flow
- 1 February 2004
- journal article
- research article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 24 (2), 159-166
- https://doi.org/10.1097/01.wcb.0000100062.36077.84
Abstract
There has been considerable interest in the use of thrombin inhibitors to reduce the occurrence of stroke or to potentiate tissue plasminogen activator-induced reperfusion. However, there is growing evidence that thrombin may also have extravascular effects that influence ischemic brain injury. Male Sprague-Dawley rats were subjected to either 90 minutes of temporary middle cerebral artery (MCA) occlusion or sham operation to examine thrombin and protease activated receptor-1 (PAR-1) expression. In another set of rats, the MCA was occluded for 90 minutes and 10 U of hirudin or the same volume of vehicle was injected into the caudate followed by reperfusion for up to 28 days, to test the effects of local thrombin inhibition on ischemic damage, neurologic outcome and cerebral blood flow (CBF). Thrombin immunoreactivity was increased in the ischemic caudate at 4 and 24 hours, whereas PAR-1 expression was unchanged. Hirudin reduced infarct volume in the caudate at 24 hours (79 ± 41 vs. 115 ± 20 mm3, P < 0.05) and resulted in a larger residual tissue volume in the caudate at 28 days (17.6 ± 3.9 vs. 11.8 ± 6.3 mm3, P < 0.05). Hirudin treatment also had a beneficial effect on body weight and ameliorated neurologic deficits tested by forelimb placing and forelimb use asymmetry during 28 days survival. These beneficial effects of hirudin were not associated with improved regional CBF during reperfusion. These results suggest that, in addition to their effects on coagulation and circulation, thrombin inhibitors also have direct neuroprotective properties and may be considered in stroke therapy.Keywords
This publication has 26 references indexed in Scilit:
- Hirudin As Alternative Anticoagulant- A Historical ReviewSeminars in Thrombosis and Hemostasis, 2002
- Behavioral Tests After Intracerebral Hemorrhage in the RatStroke, 2002
- Thrombin-Receptor Activation and Thrombin-Induced Brain ToleranceJournal of Cerebral Blood Flow & Metabolism, 2002
- Thrombin signalling and protease-activated receptorsNature, 2000
- Potentiation of NMDA Receptor Function by the Serine Protease ThrombinJournal of Neuroscience, 2000
- The problem of assessing effective neuroprotection in experimental cerebral ischemiaProgress in Neurobiology, 1998
- Thrombin Induces Apoptosis in Cultured Neurons and Astrocytes via a Pathway Requiring Tyrosine Kinase and RhoA ActivitiesJournal of Neuroscience, 1997
- Edema from intracerebral hemorrhage: the role of thrombinJournal of Neurosurgery, 1996
- Prothrombin mRNA is expressed by cells of the nervous systemNeuron, 1991
- Dimethylthiourea Reduces Ischemic Brain Edema without Affecting Cerebral Blood FlowJournal of Cerebral Blood Flow & Metabolism, 1990