Acta Neurochirurgica Supplements pp 357-361 | Cite as
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 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.
Keywords
Surgical brain injury MMP-9 MMP-2 Brain edemaPreview
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References
- 1.Adair JC, Charlie J, Dencoff JE, Kaye JA, Quinn JF, Camicioli RM, Stetler-Stevenson WG, Rosenberg GA (2004) Measurement of gelatinase B (MMP-9) in the cerebrospinal fluid of patients with vascular dementia and Alzheimer disease. Stroke 35(6): e159–62PubMedCrossRefGoogle Scholar
- 2.Andrews RJ, Muto RP (1992) Retraction brain ischaemia: cerebral blood flow, evoked potentials, hypotension and hyperventilation in a new animal model. Neurol Res 14:12–18PubMedGoogle Scholar
- 3.Aoki T, Sumii T, Mori T, Wang X, Lo EH (2002) Blood-brain barrier disruption and matrix metalloproteinase-9 expression during reperfusion injury: mechanical versus embolic focal ischemia in spontaneously hypertensive rats. Stroke 33(11):2711–2717PubMedCrossRefGoogle Scholar
- 4.Basso DM, Beattie MS, Bresnahan JC (1996) Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol 139: 244–256PubMedCrossRefGoogle Scholar
- 5.Castellanos M, Leira R, Serena J, Pumar JM, Lizasoain I, Castillo J, Davalos A (2003) Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke. Stroke 34(1):40–46PubMedCrossRefGoogle Scholar
- 6.Deletis V, Sala F (2001) The role of intraoperative neurophysiol-ogy in the protection or documentation of surgically-induced injury to the spinal cord. Ann N Y Acad Sci 939:137–144PubMedCrossRefGoogle Scholar
- 7.Fasano VA, Penna G (1992) [Postoperative complications in neurosurgery]. Minerva Anestesiol 58:15–21PubMedGoogle Scholar
- 8.Fujimura M, Gasche Y, Morita-Fujimura Y, Massengale J, Kawase M, Chan PH (1999) Early appearance of activated matrix metal-loproteinase-9 and blood-brain barrier disruption in mice after focal cerebral ischemia and reperfusion. Brain Res 842(1):92–100PubMedCrossRefGoogle Scholar
- 9.Garcia JH, Wagner S, Liu KF, Hu XJ (1995) Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation. Stroke 26:627–634PubMedGoogle Scholar
- 10.Gasche Y, Copin JC, Sugawara T, Fujimura M, Chan PH (2001) Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. J Cereb Blood Flow Metab 21(12):1393–400PubMedCrossRefGoogle Scholar
- 11.Hellwig D, Bertalanffy H, Bauer BL, Tirakotai W (2003) Pontine hemorrhage. J Neurosurg 99:796–797PubMedGoogle Scholar
- 12.Hernesniemi J, Leivo S (1996) Management outcome in third ventricular colloid cysts in a defined population: a series of 40 patients treated mainly by transcallosal microsurgery. Surg Neurol 45:2–14PubMedCrossRefGoogle Scholar
- 13.Jadhav V, Matchett G, Hsu FP, Zhang JH (2007) Inhibition of Src tyrosine kinase and effect on outcomes in a new in vivo model of surgically induced brain injury. J Neurosurg 106(4):680–686PubMedCrossRefGoogle Scholar
- 14.Jadhav V, Solaroglu I, Obenaus A, Zhang JH (2007) Neuro-protection against surgically induced brain injury. Surg Neurol 67 (1):15–20 discussion 20. ReviewPubMedCrossRefGoogle Scholar
- 15.Jadhav V, Jabre A, Lin SZ, Lee TJ (2004) EP1- and EP3-receptors mediate prostaglandin E2-induced constriction of porcine large cerebral arteries. J Cereb Blood Flow Metab 24:1305–1316PubMedCrossRefGoogle Scholar
- 16.Justicia C, Panes J, Sole S, Cervera A, Deulofeu R, Chamorro A, Planas AM (2003) Neutrophil infiltration increases matrix metal-loproteinase-9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats. J Cereb Blood Flow Metab 23(12):1430–1440PubMedCrossRefGoogle Scholar
- 17.Kaczorowski SL, Schiding JK, Toth CA, Kochanek PM (1995) Effect of soluble complement receptor-1 on neutrophil accumulation after traumatic brain injury in rats. J Cereb Blood Flow Metab 15(5):860–864PubMedGoogle Scholar
- 18.Lee SR, Tsuji K, Lee SR, Lo EH (2004) Role of matrix metalloproteinases in delayed neuronal damage after transient global cerebral ischemia. J Neurosci 24(3):671–678PubMedCrossRefGoogle Scholar
- 19.Manninen PH, Raman SK, Boyle K, el-Beheiry H (1999) Early postoperative complications following neurosurgical procedures. Can J Anaesth 46:7–14PubMedCrossRefGoogle Scholar
- 20.Matchett G, Hahn J, Obenaus A, Zhang J (2006) Surgically induced brain injury in rats: The effect of erythropoietin. J Neurosci Methods 158(2):234–241PubMedCrossRefGoogle Scholar
- 21.Rosenberg GA, Estrada EY, Dencoff JE (1998) Matrix metal-loproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain. Stroke 29(10):2189–2195PubMedGoogle Scholar
- 22.Solaroglu I, Beskonakli E, Kaptanoglu E, Okutan O, Ak F, Taskin Y (2004) Transcortical-transventricular approach in colloid cysts of the third ventricle: surgical experience with 26 cases. Neuro-surg Rev 27:89–92CrossRefGoogle Scholar
- 23.Tommasino C (1992) [Postoperative cerebral edema. Physiopa-thology of the edema and medical therapy]. Minerva Anestesiol 58:35–42PubMedGoogle Scholar
- 24.Yang Y, Estrada EY, Thompson JF, Liu W, Rosenberg GA (2007) Matrix metalloproteinase-mediated disruption of tight junction proteins in cerebral vessels is reversed by synthetic matrix metalloproteinase inhibitor in focal ischemia in rat. J Cereb Blood Flow Metab 27(4):697–709PubMedGoogle Scholar
- 25.Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH (2000) Effects of matrix metal-loproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20(18):7037–7042PubMedGoogle Scholar
- 26.Xi G, Hua Y, Keep RF, Younger JG, Hoff JT (2002) Brain edema after intracerebral hemorrhage: the effects of systemic complement depletion. Acta Neurochir Suppl 81:253–256PubMedGoogle Scholar