Matrix metalloproteinase inhibition attenuates brain edema after surgical brain injury.
BACKGROUND
Neurosurgical operations can result in inevitable brain injury due to the procedure itself. This surgical brain injury (SBI) can cause post-operative complications such as brain edema following blood-brain barrier (BBB) disruption leading to neurological deficits.


METHODS
We tested whether inhibition of matrix metalloproteinases (MMPs) 9 and 2 provided neuroprotection against SBI. A rodent SBI model, which involves a partial frontal lobe resection, was used to evaluate two treatment regimens of MMP inhibitor-1 (inhibitor of MMP-9 and MMP-2); a single dose (5 mg/kg, pretreatment) and daily dose treatment (5 mg/kg x 3, pre- and post-treatment). Postoperative assessment at different time periods included brain water content (brain edema), immunohistochemical analysis, zymography for MMP enzymatic activity, and neurological assessment.


RESULTS
The results indicate that SBI caused localized edema around the site of surgical resection with concomitant increase in MMP-9 and MMP-2 activity. Both treatment regimens with MMP inhibitor-1 decreased brain edema and attenuated the rise in MMP-9 and MMP-2 activity. An increased expression of MMP-9 was also seen in the neurons and neutrophils in the affected brain tissue at the periphery of surgical resection.


CONCLUSIONS
The study suggests a potential role for MMP inhibition as preoperative therapy before neurosurgical procedures.
Jadhav
Vikram
V
Department of Physiology and Pharmacology, Loma Linda University, RH 228, 11041 Campus Street, Loma Linda, CA, USA.
Yamaguchi
Mitsuo
M
Obenaus
Andre
A
Zhang
John H
JH
D000818:Animals; D001929:Brain Edema / Q000209:etiology* / Q000517:prevention & control*; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D007839:Functional Laterality; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009460:Neurologic Examination / Q000379:methods; D009195:Peroxidase / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011506:Proteins / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D011506:Proteins; C073882:phosphoprotein phosphatase inhibitor 1; D009195:Peroxidase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D010751:Phosphopyruvate Hydratase