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Matrix metalloproteinase inhibition attenuates brain edema after surgical brain injury
Vikram Jadhav1, Mitsuo Yamaguchi, Andre Obenaus
1Department of Physiology and Pharmacology, Loma Linda University, RH 228, 11041 Campus Street, Loma Linda, CA, USA.
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.
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.
