Effects of matrix metalloproteinase 9 inhibition on the blood brain barrier and inflammation in rats following cardiopulmonary resuscitation.
BACKGROUND
Neuroprotective strategies following cardiopulmonary resuscitation (CPR) are an important focus in emergency and critical care medicine. Matrix metalloproteinases (MMPs), especially MMP9 attracted much attention because of its function in focal brain ischemia/reperfusion injury. In the focal cerebral ischemia model in rats, SB-3CT can suppress the expression of MMP9, relieving brain edema, and there was no studies on global cerebral ischemia-reperfusion injury after CPR.


METHODS
One hundred and twenty rats were randomly assigned to sham-operated (n = 40), resuscitation treatment (n = 40), and resuscitation control (n = 40) groups. Sham-operated group rats were anesthetized only and intubated tracheally, while the resuscitation treatment and resuscitation control groups also received cardiac arrest by asphyxiation. In the resuscitation treatment group, SB-3CT was injected intraperitoneally after restoring spontaneous circulation (ROSC), defined as restoration of supraventricular rhythm and mean arterial pressure (MAP) > or = 60 mm Hg for more than 5 minutes. The resuscitation control group also implemented ROSC without injection of SB-3CT. The rats were executed and samples were taken immediately after death, then at 3, 9, 24, and 48 hours (n = 8). Brain tissue expression of MMP9 protein, MMP9 mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 was measured, and the brain tissue ultramicrostructure studied with electron microscopy.


RESULTS
In the resuscitation control group, brain tissue expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 were significantly elevated at 3 hours, and peaked at 24 hours after resuscitation, when compared with the sham-operated group (P < 0.05). Tissue ultramicrostructure also changed in the resuscitation control group. By contrast, although all these indexes were increased in the resuscitation treatment group compared with the sham-operated group (P < 0.05), they were lower than in the resuscitation control group (P < 0.05).


CONCLUSIONS
Expression of MMP9 protein and mRNA, water content, Evans blue content, TNF-alpha, IL-1, and IL-6 increased in rat brain tissue after CPR, indicating disruption of the blood-brain barrier and excess inflammatory reaction. MMP9 expression was reduced with SB-3CT, resulting in reduced brain injury.
He
Zhi-jie
ZJ
Department of ICU, the Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510120, China. hezhijie2004@126.com
Huang
Zi-tong
ZT
Chen
Xiao-tong
XT
Zou
Zi-jun
ZJ
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000276:immunology / Q000648:ultrastructure; D016887:Cardiopulmonary Resuscitation; D016207:Cytokines / Q000032:analysis; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013450:Sulfones / Q000494:pharmacology*
D016207:Cytokines; D006573:Heterocyclic Compounds, 1-Ring; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C429533:SB 3CT compound; D013450:Sulfones; D020780:Matrix Metalloproteinase 9