Experimental intracerebral hematoma in the rat: characterization by sequential magnetic resonance imaging, behavior, and histopathology. Effect of albumin therapy

Abstract

We characterized acute intracerebral hemorrhage (ICH) in the rat by sequential magnetic resonance imaging (MRI) and correlated MRI findings with neurobehavior and histopathology. In addition, we investigated whether albumin treatment would reduce ICH-induced brain injury. ICH was produced in rats by a double-injection method in which 45 microl of fresh arterial blood was injected into the right striatum. Susceptibility-weighted (SWI) and T2-weighted (T2WI) MRI was carried out on a 4.7T magnet at 0-1 h, 6 h, 24 h, 72 h, and 7 days after ICH. Animals were treated with either 25% human albumin, 1.25 g/kg, or saline vehicle i.v. at 90 min after ICH. Neurological status was evaluated before ICH and after treatment (at 4 h, 24 h, 48 h, 72 h, and 7 days). Brains were then perfusion-fixed, re-imaged on an 11.7T magnet, and studied by histopathology and immunochemistry. MRI revealed a consistent hematoma involving the striatum and overlying corpus callosum, with significant volume changes over time. Lesion volumes computed from T2WI images and by histopathology agreed closely with one another and were highly correlated (p=0.002). SWI lesion volumes were also highly correlated to histological volumes (p<0.001) but overestimated histological hematoma volume by approximately 5-fold. Albumin treatment significantly improved neurological scores compared to saline at 72 h (3.8+/-0.6 vs. 1.5+/-0.7) and 7 days (3.8+/-0.4 vs. 1.3+/-0.5, respectively, p<0.05), but did not affect histological or MRI lesion volumes. Taken together, sequential MRI plus histopathology provides a comprehensive characterization of experimental ICH. Albumin treatment improves neurological deficit after ICH but does not affect MRI or histological hematoma size.