Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in rats

The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin‐induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild...

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Bibliographic Details
Published in:Journal of neuroscience research 2006-02, Vol.83 (3), p.469-475
Main Authors: Henrich-Noack, Petra, Striggow, Frank, Reiser, Georg, Reymann, Klaus G.
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal
Brain Infarction - etiology
Brain Infarction - prevention & control
Disease Progression
Dose-Response Relationship, Drug
Drug Administration Schedule
Endothelin-1
focal ischemia
Hemostatics - administration & dosage
Hypoxia-Ischemia, Brain - chemically induced
Hypoxia-Ischemia, Brain - complications
Hypoxia-Ischemia, Brain - pathology
infarct
Male
neuroprotection
Rats
Rats, Sprague-Dawley
Statistics, Nonparametric
stroke
Thrombin - administration & dosage
Time Factors
tolerance
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Summary:The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin‐induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild ischemia to investigate the effects of preischemic intracerebral thrombin injection on neural damage. By intracerebral injection of endothelin‐1 in freely moving animals, we achieved middle cerebral artery occlusion (MCAO), and 7 days postischemia we performed histological quantification of the infarct areas. Thrombin was injected as a preconditioning stimulus intracerebrally 7 days or 2 and 3 days before ischemia. For acute treatment, thrombin was injected 20 min before MCAO. Thrombin induced significant neuroprotection when given 7 days before endothelin‐1‐induced MCAO but was deleterious when given 2 and 3 days before the insult. The deleterious effect was not seen when thrombin was given acutely before ischemia. Our data demonstrate that preconditioning with thrombin can protect against damage or worsen ischemic damage. Its effect depended on the time interval between thrombin injection and insult. A low dose of thrombin did not induce a major deleterious effect in the acute phase of the infarct development after mild transient ischemia. © 2006 Wiley‐Liss, Inc.
ISSN:0360-4012
1097-4547
DOI:10.1002/jnr.20746