Matrix metalloproteinase inhibition attenuates brain edema after surgical brain injury

Abstract

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 metal-loproteinases (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. Findings 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. © 2008 Springer-Verlag/Wien.