| Spontaneous intracerebral hemorrhage accounts for 10-20% of all strokes, it is associated with high mortality and morbility. Many patients with an intracerebral hematoma deteriorate progressively after hemorrhage because of the accumulation of edema fluid around the mass, better understanding of its pathophysiology might improve clinical management of these patients. Thrombin has been implicated in brain injury and edema formation after ICH. Most attention has focused on thrombin formation during clotting. At the same time, the kallikrein-kinin system is similarly involved in cerebral edema progression. The scarce amount of research in ICH contrasts with the abundance of experimental, clinical and therapeutical studies in cerebral ischemia, leading to the current research of edema formation due to intracerebral hemorrhage.Objective: The first part of this study sought to determine whether or not thrombin cause edema formation or contribute to it, and to see if the edema response to thrombin could be prevented by adding a specific thrombin inhibitor, hirudin, or a calcium antagonist, nimodipine. If this process could be identified, blockade of edema formation through the coagulation cascade might be possible. The second part was concerned specifically with the involvement of bradykinin on vasogenic edema formation after ICH, and evaluated the therapeutic effect of aprotinin, a broad-spectrum serine protease inhibitor on intracerebral hemorrhage.Method: 1.Adult SD rats were subjected differently to stereotaxic caudate nucleus injections of normal saline low and high dose thrombin, or its mixture with hirudin, intraperitoneally injection of nimodipine(50ug/100mg body weight) followed by high dose thrombin. Five time points: 4hr, 24hr, 48hr, 3d, 7d were used in each group. The rats were sacrificed by decapitation at the pointed time course. The brains were removed and a coronal slice was cut. Brain edema was observed using a "dry-wet-weighing technique" and a microscopy(HE staining).2.A cohort study was conducted in patients with spontaneous ICH admitted consecutively to the hospital. A total of 30 patients eligible for inclusion criteria were randomly divided into two groups. The control group received traditional mannitol for anti-brain edema therapy. Additionally, the experimental group received intravenous administration of aprotinin from ICH onset. Head CT scan and the score of neurological function deficit signs were performed on all patients at entry into the study and two weeks after inclusion. The two groups were compared with the indexes of the score difference and the hematoma absorptive rate.Result: 1.This study showed that saline and low dose thrombin did not induce edema. High dose thrombin resulted in obvious brain edema as early as 4hrs after injection, and increased progressively, remained elevated for 24 to 48 hours(P<0.05 ), then begin to resolve. Brain water content in brain tissue were reduced in the hirudin or nimodipine treated rats as compared to other groups, and brain swelling were alleviated. 2.The average decreased score of neurological functional deficit and the hematoma absorptive rats with treatment of aprotinin were better than that in the control group in ICH patients.Conclusion: 1.High dose thrombin cause brain edema obviously as early as 4 hours, reaches a peak level and plateaus during 24 to 48hours, then begins to resolve and return to baseline levels. The study indicate that thrombin, an essential component in the coagulation cascade, is directly involved in the process of brain edema formation following ICH. Through its receptors, thrombin causes retraction of cell processes and istoxic to neurons in a dose-dependent manner. Hirudin is the most potent and specific thrombin inhibitor. In addition to inhibition of water accumulation, the effectiveness of hirudin as an inhibitor of brain edema from intracerebral hematomas provides further evidence that thrombin plays an important role in the pathogenesis of edema resulting from a parenchymal clot, and therefore r... |
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