Summary Of Animal Species And Ich Induction Methods

In this review we have described the various animal species that have been employed in ICH research. In addition, we have discussed the several methodologies that have been employed to produce intracerebral hematomas, presenting the pros and cons of the individual species and the ICH induction techniques. In this section, we have summarized these advantages and disadvantages and have suggested the "best" models and methods based on the goals of the study, the experimental plan, the desired hematoma volumes, and the expense.

Rodents have the advantage of being the most commonly used species in ICH research. The literature on neurobehavioral testing is well developed and the reagents for immunocy-tochemistry and molecular biology have been extensively studied. The recent development of mouse ICH models enables the study of transgenic and knockout animals, which is a clear advantage for uncovering the detailed molecular pathophysiologic events underlying the development of tissue injury following ICH.

Large animals (pigs, dogs, and primates) have certain advantages over rodents in ICH research. These include their large gyrated brains with a significant amount of white matter. Large animals enable the induction of greater hematoma volumes to test the efficacy of surgical evacuation techniques or combined surgery and drug treatments. The well-developed frontal white matter in the pig has been especially useful for pathophysiologic studies of ICH-induced white-matter injury as well as surgical clot evacuation studies. In addition, pigs have the advantage as compared to dogs and cats that they are less expensive to purchase and are considered non-companion animals. Primates are exceedingly expensive to purchase and house and require special facilities and veterinary care.

Regarding the methods for inducing an intracerebral hematoma, as described above, i.e., the two commonly used methods are the classical blood infusion method and the collagenase injection method. Neither method exactly models the human event, i.e., sudden arterial rupture with a rapid intraparenchymal accumulation of blood. Currently, there is no model of intra-cerebral blood vessel rupture to induce ICH. Although both the direct blood infusion model and the collagenase model have their artificialities, the arterial blood infusion through an indwelling catheter described throughout the review is generally considered to be the method of choice for inducing experimental ICH. The use of the bacterial collagenase enzyme to "dissolve" the extracellular matrix has been considered to be more artificial due to its severe inflammatory response and secondary pathophysiology that occurs in the setting of an already damaged brain parenchyma.

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