Blood-brain barrier disruption in experimental focal ischemia: comparison between in vivo MRI and immunocytochemistry.
The definition of blood-brain barrier (BBB) damage in cerebral ischemia using contrast-enhanced MRI has not been clearly correlated to the spread of edema or other histological measures of barrier disruption. In this study, we used a rabbit model of focal cerebral ischemia to compare GdDTPA-enhanced MRI with spin-echo images of brain injury and immunocytochemical detection of BBB damage and vasogenic edema. After 4 h of transient ischemia followed by 6 h of reperfusion, in vivo T2W and T1W images were obtained in a 1.5 T magnet using a 3-inch surface coil. After MRI, the animals were sacrificed and anti-serum protein (IgG) monoclonal antibodies were used to detect regions of increased BBB permeability to serum proteins. Ischemic neuronal damage was confirmed with cresyl-violet histology. T2W scans showed focal regions of increased signal intensity in the ischemic hemisphere (17.0 +/- 4.1%) that primarily involved the cortex and striatum. T1W scans showed corresponding regions of hypointensity but demonstrated, in general, smaller lesion sizes (10.1 +/- 2.9%). GdDTPA-enhanced images showed variable areas of BBB disruption that included regions of intense leakage as well as lesions that only showed subtle enhancement along the periphery of damaged tissue. It appeared that large and more severe lesions corresponded to peripheral enhancement whereas smaller lesions showed central parenchymal enhancement. The extent of MR contrast enhancement did not correlate well with immunocytochemical images of serum protein leakage. Anti-IgG stains demonstrated widespread regions of BBB damage corresponding with areas of damaged neurons that appeared pyknotic on cresyl-violet sections.(ABSTRACT TRUNCATED AT 250 WORDS)
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Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital, Harvard Medical School, Charlestown 02129.
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Matsumoto
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Kowall
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D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D001812:Blood-Brain Barrier; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D003287:Contrast Media; D019786:Gadolinium DTPA; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives; D011817:Rabbits
D001798:Blood Proteins; D003287:Contrast Media; D009942:Organometallic Compounds; D004369:Pentetic Acid; D019786:Gadolinium DTPA