Hemorrhagic Stroke Model

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Several animal models of intracerebral hemorrhage (ICH) have been developed in mice, rats, rabbits, cats, and nonhuman primates. A widely used method that produces ICH by injection of bacterial collagenase into the basal ganglia was first introduced in the rat and was subsequently studied in the mouse (Rosenberg et al., 1990; Clark et al., 1998). This enzyme digests the collagen present in the basal lamina of blood vessels and causes bleeding into the surrounding brain tissue. However, another study demonstrated that bacterial collagenase causes a significant inflammatory reaction and likely differs from the mechanism that produces ICH in humans (Del Bigio et al., 1996). A second model uses the infusion of autologous blood into the brain parenchyma. This model was designed to mimic the natural events that occur with spontaneous ICH in humans. However, it produces hematomas of varying size because of ventricular rupture and the backflow of infused blood along the needle track, which leads to intraventricular and/or subarachnoid leakage of blood. Recently, a double injection ICH model has been developed in which a small amount of blood is infused into the striatum at a slow rate to allow blood clotting along the needle track; the remaining blood is then infused to generate the hematoma. This method creates a reproducible hematoma volume suitable for study of the pathophysiology and treatment of ICH (Belayev et al., 2003). A widely used experimental procedure for ICH in mice is as follows. The animal is placed in a stereotactic frame. A 30-gauge stainless steel cannula is introduced through a burr hole into the left striatum (2 mm lateral to midline, 1 mm anterior to bregma, depth 4 mm below the surface of the skull) and the mouse receives an injection of either whole blood (taken from a donor mouse) or CSF (10-15 ^l) over several minutes, and the injection cannula is slowly withdrawn 10 minutes after the injection.

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