Review articleExperimental animal models of intracerebral hemorrhage☆
Section snippets
Brain pathologic responses to intracerebral hemorrhage in animal models
In general, the brain pathologic responses to an ICH are comparable in human beings and experimental animal models [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. Three stages of sequential change that occur around an ICH were originally defined by Spatz [15] and include initial deformation, followed by edema and necrosis, and finally clot absorption and scar or cavity formation. In the rat, regions of pallor and spongiform change develop adjacent to clots within 2 hours [8]. By 6 to 15
Intracerebral blood infusion intracerebral hemorrhage models
Intraparenchymal infusion (or injection) of autologous blood is a straightforward and effective technique to produce an intracerebral hematoma. Although this method does not specifically reproduce the bleeding event of spontaneous ICH in human beings (ie, punctate blood vessel rupture), it is controllable and reproducible. One disadvantage of blood infusion models is the potential for ventricular rupture as well as for backflow of infused blood along the needle track [32], [33]. Such events can
Bacterial collagenase model
This model introduced by Rosenberg and his colleagues [3], [4], [76] utilizes the local injection of bacterial collagenase into the basal ganglia to induce an intracerebral bleed. Collagenases are proteolytic enzymes present intracellularly in an inactive form. They are secreted at sites of inflammation by mononuclear cells and some tumor cells. Collagen, the substrate for this enzyme, is known to be present in the basal lamina of cerebral blood vessels. Collagenase dissolves the extracellular
Ischemia-reperfusion hemorrhage model
In 1976, Laurent et al [80] described an interesting ICH model in Rhesus monkeys in which hematomas were induced during the vasoproliferative stages of maturing infarction. In this model, MAP elevation at 5 days induced by cerebral vasoconstriction after permanent middle cerebral artery occlusion caused hemorrhagic infarct conversion, whereas cerebral vasodilation caused intracerebral hematoma formation. No further studies have been reported with this model.
Summary
Experimental animal ICH models are able to reproduce the overall important pathophysiologic events documented in human ICH, including edema development, markedly reduced metabolism, and tissue pathologic responses. Thus, ICH models serve as an important tool for new understanding of the mechanisms underlying brain injury after an intracerebral bleed. Currently, ongoing studies in several laboratories using these models investigating secondary inflammatory responses as well as intracellular
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The studies described herein from the authors' laboratory were supported by funding from the National Institute of Neurological Diseases and Stroke (R01NS-30652) and the Department of Veterans Affairs Medical Research Service.