Ischemic Blood Flow in the Brain pp 57-63 | Cite as
Proteolytic Opening of the Blood-Brain Barrier During Neuroinflammation
Summary
Matrix metalloproteinases (MMPs) have been shown to produce proteolytic opening of the blood-brain barrier (BBB) during a neuroinflammatory response. Cerebral ischemia with reperfusion causes a biphasic opening of the BBB that is associated with increases in the MMPs. We used immunohistochemistry to determine the cellular location of the MMPs in ischemic brain tissue after reperfusion. Adult Wistar-Kyoto rats (WKY) underwent a middle cerebral artery occlusion (MCAO) with the suture method. Brain uptake of radiolabeled sucrose was used to study the time course of the BBB opening. Zymograms were used to measure the type IV collagenases or gelatinases. Immunostaining was done with antibodies to gelatinase A (MMP-2), gelatinase B (MMP-9), and stromelysin (MMP-3). We found a biphasic opening of the BBB with a transient opening after 3h of reperfusion and a more extensive injury at 48 h. MMP-2 was associated with the initial opening and MMP-9 with the later one.
Immunohistochemistry of normal brain showed MMP-2 in the astrocytic end-feet abutting blood vessels. MMP-9 was mainly in endothelial cells in the ischemic region, whereas MMP-3 was in the perivascular cells. MMPs are important for reperfusion injury and contribute to the brain edema and intracerebral hemorrhage.
Key words
Blood-brain barrier Brain edema Cerebral ischemia Matrix metalloproteinases Reperfusion injuryPreview
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