Gelatinase B modulates selective opening of the blood-brain barrier during inflammation
| Autor: | Gary A. Rosenberg, Sheila Mun-Bryce |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Lipopolysaccharides
Male Pathology medicine.medical_specialty Lipopolysaccharide Physiology Central nervous system Inflammation Biology Matrix metalloproteinase Blood–brain barrier Rats Sprague-Dawley Central nervous system disease chemistry.chemical_compound Immune system Physiology (medical) medicine Animals Collagenases Neuroinflammation Tumor Necrosis Factor-alpha medicine.disease Rats medicine.anatomical_structure Matrix Metalloproteinase 9 chemistry Blood-Brain Barrier Brain Injuries Cancer research medicine.symptom |
| Zdroj: | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 274:R1203-R1211 |
| ISSN: | 1522-1490 0363-6119 |
| DOI: | 10.1152/ajpregu.1998.274.5.r1203 |
| Popis: | Matrix metalloproteinases (MMPs) are associated with neuroinflammatory diseases, and blood-brain barrier damage is a pathophysiological consequence of central nervous system inflammation. We examined whether an increase in MMP production is coupled with the breakdown of blood-brain barrier integrity in the lipopolysaccharide (LPS)-injured brain. Rat brain stimulated with LPS showed a significant rise in gelatinase B (MMP-9) production at 24 h compared with either tumor necrosis factor-α (TNF-α) or saline-injected controls. Latent 92-kDa gelatinase B was detected by 4 h, peaked at 8 h, and persisted for 24 h after LPS injection. Production of the active 84-kDa form of gelatinase B was less pronounced, but paralleled 92-kDa enzyme expression. Breakdown in blood-brain barrier integrity, measured by the infiltration of radiolabeled exogenous markers into the brain, was significant to [14C]sucrose (molecular mass 342 Da) and [14C]dextran (molecular mass 50–90 kDa) molecules in LPS-injected animals compared with saline-injected controls. The extent of MMP involvement in barrier permeability was examined in animals treated with the MMP inhibitor BB-1101. A significant drop in gelatinase A and B production was detected in LPS-injured animals receiving BB-1101 compared with untreated animals. This MMP inhibitor also reduced [14C]sucrose uptake in LPS-injected animals, but had no effect on [14C]dextran uptake. MMP production is upregulated in LPS-injured brain tissue and is instrumental in regulating the size-differentiated opening of the blood-brain barrier during acute neuroinflammation. |
| Databáze: | OpenAIRE |
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