PMID- 1381261 OWN - NLM STAT- MEDLINE DCOM- 19921007 LR - 20190613 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 576 IP - 2 DP - 1992 Apr 3 TI - TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase. PG - 203-7 AB - Intracerebral hemorrhage occurs in tumors, stroke and head trauma. Proteolysis of the extracellular matrix around cerebral capillaries by naturally occurring mammalian 72-kDa type IV collagenase may initiate this pathologic event. To investigate this hypothesis adult rats underwent intracerebral injection of type IV collagenase purified from human melanoma cells. Histologically, at 4 h there was perivascular cellular infiltration with hemorrhage, and by 24 h there was infarction with necrosis, edema and hemorrhage. Ultrastructurally, the basal lamina of endothelial cells was disrupted at 2 h. Brain uptake of [14C]dextran and [3H]sucrose increased after intracerebral injection of type IV collagenase compared to controls (P less than 0.0001). Tissue inhibitor of metalloproteinase-2 (TIMP-2) reduced the tracer uptake (P less than 0.02). Metalloproteinase inhibitors reduce extracellular matrix proteolysis and protect the blood-brain barrier. FAU - Rosenberg, G A AU - Rosenberg GA AD - Department of Neurology, University of New Mexico School of Medicine, Albuquerque 87131-5281. FAU - Kornfeld, M AU - Kornfeld M FAU - Estrada, E AU - Estrada E FAU - Kelley, R O AU - Kelley RO FAU - Liotta, L A AU - Liotta LA FAU - Stetler-Stevenson, W G AU - Stetler-Stevenson WG LA - eng GR - R01-NS21169/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Dextrans) RN - 0 (Neoplasm Proteins) RN - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2) RN - 57-50-1 (Sucrose) RN - EC 3.4.24.3 (Microbial Collagenase) SB - IM MH - Analysis of Variance MH - Animals MH - Biological Transport/drug effects MH - Blood-Brain Barrier/*drug effects MH - Brain/drug effects/metabolism/*pathology MH - Capillaries/drug effects/pathology/ultrastructure MH - Cerebral Ventricles/drug effects/*physiology MH - Cerebrovascular Circulation/*drug effects MH - Dextrans/metabolism MH - Humans MH - Injections, Intraventricular MH - Male MH - Microbial Collagenase/administration & dosage/antagonists & inhibitors/*toxicity MH - Neoplasm Proteins/administration & dosage/*pharmacology MH - Rats MH - Rats, Inbred Strains MH - Sucrose/metabolism MH - Tissue Inhibitor of Metalloproteinase-2 EDAT- 1992/04/03 00:00 MHDA- 1992/04/03 00:01 CRDT- 1992/04/03 00:00 PHST- 1992/04/03 00:00 [pubmed] PHST- 1992/04/03 00:01 [medline] PHST- 1992/04/03 00:00 [entrez] AID - 0006-8993(92)90681-X [pii] AID - 10.1016/0006-8993(92)90681-x [doi] PST - ppublish SO - Brain Res. 1992 Apr 3;576(2):203-7. doi: 10.1016/0006-8993(92)90681-x.