Hematoma volumes in rabbits were studied using autologous blood stereotactically injected into the thalamus, and it was found that these animals would tolerate clots with a volume of 3% to 5% of their brain volume, which approximates a 50-cc clot in humans (49). In one of the earliest studies of the efficacy of hematoma removal with thrombolytics the authors demonstrated 86% efficacy in lysing intracranial hematomas with urokinase in a rabbit ICH model, whereas only 3 of the 13 controls showed evidence of hematoma resolution with saline injections into the clot (50). Furthermore, histologically, no increased damage or inflammation was noted between these animals and 22 additional rabbits treated with urokinase or saline 24 hr after clot injection. The authors concluded that urokinase could be employed safely and effectively for the lysis of intracranial hematomas and that a delay in therapy of up to 24 hr does not significantly compromise its efficacy. The efficacy of urokinase in stereotactic human ICH treatment was further demonstrated by Zuccarello et al. (51).

In a very detailed examination of the cellular activation in the perifocal reactive zone in a rabbit ICH model, Koeppen et al. (52) found that experimental hematomas resolved much more slowly after the injection of whole blood than after the injection of red blood cells, suggesting that proteins in the coagulated blood contribute to the injury process.

Imaging studies of ICH in rabbits demonstrated that susceptibility-weighted gradient-echo imaging at 1.5 T is highly sensitive in detecting hyperacute parenchymal, as well as subarachnoid and intraventricular hemorrhages (53). A rabbit lobar ICH model in which arterial pressure was used to infuse autologous blood into the deep frontal white matter, served to investigate the degree of neuronal injury inside and outside the hematoma at 24 hr (54 ).

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