Bacterial Collagenase Model

The bacterial collagenase model employs the local injection of bacterial collagenase into the basal ganglia to induce an intracerebral bleed (22,23,75) . This model mimics spontaneous ICH in humans by dissolving the extracellular matrix around capillaries, resulting in active intraparenchymal bleeding. The hemorrhage is simple to produce. The animals develop spontaneous, reproducible hemorrhages, with volumes that correlate with the amount of collagenase injected, and significant blood leakage does not develop along the needle track. A disadvantage is that bacterial collagenase introduces a significant inflammatory reaction (44,76,77) that is more intense than that observed in experimental ICH models that employ blood infusion. The inflammatory response is also more intense than that observed following human ICH (78). The collagenase model also differs from the punctate arterial rupture that produces human ICH, as the collagenase dissolves the extracellular matrix around capillaries to produce hemorrhage.

The collagenase ICH model has been used by several investigators in mouse, rat, and pig. Their reports shed light on the pathochemical events following ICH and describe several new experimental treatments for ICH that have not been examined in the blood infusion model. Recent studies have demonstrated: (i) the role of MMPs in BBB opening and edema development following collagenase-induced ICH and the effectiveness of MMP inhibitors (79,80), (i i) that select MMPs exhibit increased expression after ICH and that minocycline is neuroprotective by suppressing monocytoid cell activation and downregulating MMP-12 expression (81), and (iii) that the tripeptide macrophage/microglial inhibitory factor inhibits microglial activation and results in functional improvement when given before, as well as after, the onset of collagenase-induced ICH (82,83) . Various other reports using this model have described detailed studies of the collagenase dose effect (84) , imaging features and histopathology (76,85 ), neurobehavioral results and therapy (86-88), and influence of hyperglycemia (89) . Several drug treatments aimed at different molecular mechanisms of injury have also been studied, including free radical scavengers/spin traps (90,91), neurotransmitter receptor agonists (92,93) and antagonists (94), cytokines and inflammation (77,95-98), and neuroprotectives (99 ).

The collagenase model in rodents has also been extended to pigs (100,101), and the investigators have reported studies of somatosensory-evoked potentials elicited by electrical stimulation of the contralateral snout, as well as changes in DC-coupled potential, which was monitored in the somatosensory region following induction of ICH into the primary sensory cortex.

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