TIMP-2 reduces proteolytic opening of blood-brain barrier by type IV collagenase

Brain Res. 1992 Apr 3;576(2):203-7. doi: 10.1016/0006-8993(92)90681-x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Biological Transport / drug effects
  • Blood-Brain Barrier / drug effects*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology*
  • Capillaries / drug effects
  • Capillaries / pathology
  • Capillaries / ultrastructure
  • Cerebral Ventricles / drug effects
  • Cerebral Ventricles / physiology*
  • Cerebrovascular Circulation / drug effects*
  • Dextrans / metabolism
  • Humans
  • Injections, Intraventricular
  • Male
  • Microbial Collagenase / administration & dosage
  • Microbial Collagenase / antagonists & inhibitors
  • Microbial Collagenase / toxicity*
  • Neoplasm Proteins / administration & dosage
  • Neoplasm Proteins / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Sucrose / metabolism
  • Tissue Inhibitor of Metalloproteinase-2

Substances

  • Dextrans
  • Neoplasm Proteins
  • Tissue Inhibitor of Metalloproteinase-2
  • Sucrose
  • Microbial Collagenase