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.