Intracerebral hemorrhage (ICH) has been modeled in the laboratory with the intracerebral injection of autologous blood, injection of emboli, or proteolysis of the basal lamina surrounding cerebral capillaries by bacterial collagenase (BC). Selection of the model depends on the concept of the pathophysiology behind the bleeding. Modeling a rapidly progressive bleed without excessive tissue destruction can be done by the injection of autologous blood. Injection of small blood clots into the carotid artery of the rabbit mimics an embolic stroke with hemorrhagic transformation. BC produces a highly reproducible model of intracerebral bleeding that evolves over several hours, produces inflammation around the lesion, and slowly resolves, simulating the process that has been observed to occur in human studies of serially imaged patients with ICH. BC initiates an injury that is propagated by the production of endogenous proteolytic enzymes of the matrix metalloproteinase (MMP) gene family. The inflammatory response, which is seen in both the BC model and the autologous blood model, is an important part of the pathological changes produced in the brain by the disruption of the blood vessels and brain edema. MMP inhibitors reduce the damage to the brain by the hemorrhagic mass lesion. A number of other therapeutic agents reduce injury in BC-induced ICH.
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References
Caplan LR. Intracerebral haemorrhage. Lancet 1992;339:656–658.
Zulch KJ, Minckler J. Hemorrhage, thrombosis, embolism. In: Pathology of the Nervous System. New York: McGraw-Hill Book Corp., 1971:1499–1535.
Brott T, Broderick J, Kothari R, et al. Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1–5.
Godeau G, Robert AM. Mechanism of action of collagenase on the blood-brain barrier permeability. Increase of endothelial cell pinocytotic activity as shown with horse-radish peroxidase as a tracer. Cell Biol Int Rep 1979;3:747–751.
Rosenberg GA, Estrada E, Wesley M, Kyner WT. Autoradiographic patterns of brain interstitial fluid flow after collagenase-induced hemorrhage in rat. Acta Neurochirurgica 1990;51:280–282.
Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M. Collagenase-induced intracerebral hemorrhage in rats. Stroke 1990;21:801–807.
Brown MS, Kornfeld M, Mun-Bryce S, Sibbitt RR, Rosenberg GA. Comparison of magnetic resonance imaging and histology in collagenase-induced hemorrhage in the rat. J Neuroimaging 1995;5:23–33.
Del Bigio MR, Yan HJ, Buist R, Peeling J. Experimental intracerebral hemorrhage in rats. Magnetic resonance imaging and histopathological correlates. Stroke 1996;27:2312–2319; discussion 2319–2312.
Tang J, Liu J, Zhou C, et al. Mmp-9 deficiency enhances collagenase-induced intracerebral hemorrhage and brain injury in mutant mice. J Cereb Blood Flow Metab 2004;24:1133–1145.
Grossetete M, Rosenberg GA. Matrix metalloproteinase inhibition facilitates cell death in intracerebral hemorrhage in mouse. J Cereb Blood Flow Metab 2008;28:752–763.
Rosenberg GA, Navratil M. Metalloproteinase inhibition blocks edema in intracer-ebral hemorrhage in the rat. Neurology 1997;48:921–926.
Wang J, Tsirka SE. Neuroprotection by inhibition of matrix metalloproteinases in a mouse model of intracerebral haemorrhage. Brain 2005;128:1622–1633.
Rosenberg GA, Scremin O, Estrada E, Kyner WT. Arginine vasopressin V1-antagonist and atrial natriuretic peptide reduce hemorrhagic brain edema in rats. Stroke 1992;23:1767–1773.
Zazulia AR, Diringer MN, Videen TO, et al. Hypoperfusion without ischemia surrounding acute intracerebral hemorrhage. J Cereb Blood Flow Metab 2001;21:804– 810.
Rosenberg GA, Navratil MJ. (S)-emopamil reduces brain edema from collagenase-induced hemorrhage in rats. Stroke 1994;25:2067–2071.
Lyden PD, Jackson-Friedman C, Lonzo-Doktor L. Medical therapy for intracer-ebral hematoma with the gamma-aminobutyric acid-A agonist muscimol. Stroke 1997;28:387–391.
Clark W, Gunion-Rinker L, Lessov N, Hazel K. Citicoline treatment for experimental intracerebral hemorrhage in mice. Stroke 1998;29:2136–2140.
Mayne M, Ni W, Yan HJ, et al. Antisense oligodeoxynucleotide inhibition of tumor necrosis factor-alpha expression is neuroprotective after intracerebral hemorrhage. Stroke 2001;32:240–248.
Peeling J, Del Bigio MR, Corbett D, Green AR, Jackson DM. Efficacy of disodium 4-[(tert-butylimino)methyl]benzene-1,3-disulfonateN-oxide (NXY-059), a free radical trapping agent, in a rat model of hemorrhagic stroke. Neuropharmacology 2001;40:433–439.
Peeling J, Yan HJ, Corbett D, Xue M, Del Bigio MR. Effect of FK-506 on inflammation and behavioral outcome following intracerebral hemorrhage in rat. Exp Neurol 2001;167:341–347.
Power C, Henry S, Del Bigio MR, et al. Intracerebral hemorrhage induces macro-phage activation and matrix metalloproteinases. Ann Neurol 2003;53:731–742.
Wang J, Tsirka SE. Tuftsin fragment 1–3 is beneficial when delivered after the induction of intracerebral hemorrhage. Stroke 2005;36:613–618.
Chu K, Jeong SW, Jung KH, et al. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab 2004;24:926–933.
Jung KH, Chu K, Jeong SW, et al. HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage. Stroke 2004;35:1744–1749.
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Grossetete, M., Rosenberg, G.A. (2009). Bacterial Collagenase Injection Intracerebral Hemorrhage Rat Model. In: Chen, J., Xu, Z.C., Xu, XM., Zhang, J.H. (eds) Animal Models of Acute Neurological Injuries. Springer Protocols Handbooks. Humana Press. https://doi.org/10.1007/978-1-60327-185-1_29
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DOI: https://doi.org/10.1007/978-1-60327-185-1_29
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