Models And Species Overview

The classic method of inducing ICH in experimental animals has been to directly infuse autologous blood into a specific brain region, usually the basal ganglia. This method has been employed in a variety of species, including rat, rabbit, cat, dog, pig, primate (reviews in Refs. 1 and 2), and, most recently, mouse (3,4). We have developed a large animal lobar ICH model in the pig, in which we infuse up to 3.0 mL of arterial blood into the frontal hemispheric white matter (17), and we have used this model to examine ICH pathophysiology and pathochemistry and surgical clot evacuation (17-19) (reviews in Refs. 20 and 21). A second commonly used model employs bacterial collagenase usually injected locally into the basal ganglia (22,23 ). Collagenase dissolves the extracellular matrix, leading to blood vessel rupture and an intracerebral bleed.

Overall, these models have significantly contributed to our knowledge of ICH-induced injury. Specifically, they have provided information on the roles of mass effect and elevated intracranial pressure (ICP), alterations in blood flow and metabolism, and the impact of specific blood components on brain edema formation and blood-brain barrier (BBB) disruption. Along with providing details of ICH-induced biochemical and molecular events, these models also enable testing of potential therapies, both surgical and pharmacologic.

In this chapter, the classic blood infusion models are described, and the collagenase model is reviewed. Each model section contains a detailed description of the findings that have been obtained with individual species. The brain pathologic responses to ICH that are present in the various animal models are described and compared with observations in human ICH. Lastly, the limitations of animal models and their ability to fully address various aspects of human ICH are discussed.

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