MATRIX METALLOPROTEINASE INHIBITION ATTENUATES BRAIN EDEMA IN AN IN VIVO MODEL OF SURGICALLY-INDUCED BRAIN INJURY

Abstract

OBJECTIVE: Neurosurgical procedures can result in brain injury by various means, including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause postoperative complications such as brain edema after blood-brain barrier (BBB) disruption. The present study seeks to test a matrix metalloproteinase (MMP) inhibitor for preventing postoperative brain edema and BBB disruption in an in vivo model of surgically-induced brain injury. METHODS: A rodent model of SBI was used which involves resection of a part of the right frontal lobe. A total of 89 Sprague-Dawley male rats (weight, 300-350 g) were randomly divided into four groups: 1) SBI with vehicle treatment (0.1% dimethyl sulfoxide), 2) SBI with single treatment of MMP inhibitor-1 (an inhibitor of MMP-9 and MMP-2), 3) SBI treated daily (total 3 times) with MMP inhibitor-1, and 4) sham surgical group. Postoperative assessment at different time periods included evaluation of BBB permeability, brain water content (brain edema), neurological scoring, histology, immunohistochemistry, and zymography for MMP enzymatic activity. Temporal magnetic resonance imaging studies were also performed to assess postoperative edema. RESULTS: The results indicate that SBI caused increased brain water content (ipsilateral frontal lobe) and BBB permeability compared with sham animals. Treatment with MMP inhibitor-1 attenuated MMP-9 and MMP-2 activity and decreased brain water content with preservation of the BBB. CONCLUSION: Inhibition of MMP-9 and MMP-2 attenuates brain edema and BBB disruption after SBI. The study suggests a potential role for MMP inhibition as preoperative therapy before neurosurgical procedures.