Summary
Matrix metalloproteinases (MMPs) are associated with blood-brain opening and may be involved in the pathophysiology of acute brain injury. Previous research demonstrated that knockout mice de- ficient in MMP-9 subjected to transient focal cerebral ischemia had reduced blood-brain barrier (BBB) disruption and attenuated cerebral infarction.
In this study, we examined MMP-9 up-regulation, BBB disruption, and brain edema formation after cortical impact injury in rats. Cortical contusion was induced by controlled cortical impact. Animals were sacrificed at intervals after injury. MMP up-regulation was assessed by gelatin zymography, and BBB integrity was evaluated using Evans blue dye with a spectrophotometric assay. Brain water content was measured by comparing wet and dry weights of each hemisphere as an indicator of brain edema.
Zymograms showed elevated MMP-9 as early as at 3 hours after injury, reaching a maximum at 18 hours. Peak levels of BBB disruption occurred 6 hours after injury. Brain edema became progressively more severe, peaking 24 hours after injury. Compared to control group, treatment with MMP-inhibitor GM6001 signifi- cantly reduced BBB disruption 6 hours and brain water content (85.9 ± 0.5% vs. 82.6 ± 0.3%; p < 0.05) 24 hours after injury. These findings suggest that MMP-9 may contribute to BBB disturbance and subsequent brain edema after traumatic brain injury.
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References
Arvin B, Neville LF, Barone FC, Feuerstein GZ (1996) The role of inflammation and cytokines in brain injury. Neurosci Biobehav Rev 20: 445–452
Asahi M, Wang X, Mori T, Sumii T, Jung JC, Moskowitz MA, Fini ME, Lo EH (2001) Effects of matrix metalloproteinase-9 gene knock-out on the proteolysis of blood-brain barrier and white matter components after cerebral ischemia. J Neurosci 21: 7724–7732
Colicos MA, Dash PK (1996) Apoptotic morphology of dentate gyrus granule cells following experimental cortical impact injury in rats: possible role in spatial memory deficits. Brain Res 739: 120–131
Fiotti N, Zivadinov R, Altamura N, Nasuelli D, Bratina A, Tommasi MA, Bosco A, Locatelli L, Grop A, Cazzato G, Guamieri G, Giansante C, Zorzon M (2004) MMP-9 microsatellite polymorphism and multiple sclerosis. J Neuroimmunol 152: 147–153
Katayama Y, Maeda T, Koshinaga M, Kawamata T, Tsubokawa T (1995) Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury. Brain Pathol 5: 427–435
Kawamata T, Katayama Y, Maeda T, Mori T, Aoyama N, Kikuchi T, Uwahodo Y (1997) Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats. Acta Neurochir [Suppl] 70: 191–193
Keogh B, Sheahan BJ, Atkins GJ, Mills KH (2003) Inhibition of matrix metalloproteinases ameliorates blood-brain barrier disruption and neuropathological lesions caused by avirulent Semliki Forest virus infection. Vet Immunol Immunopathol 94: 185–190
Mori T, Katayama Y, Kawamata T, et al (1996) Progressive edema formation in contused brain: Role of tissue osmolality and ion concentrations. Adv Neurotrauma Res 8: 15–18
Mori T, Wang X, Kline AE, Siao CJ, Dixon CE, Tsirka SE, Lo EH (2001) Reduced cortical injury and edema in tissue plasminogen activator knockout mice after brain trauma. Neuroreport 12: 4117–4120
Mori T, Wang X, Aoki T, Lo EH (2002) Downregulation of matrix metalloproteinase-9 and attenuation of edema via inhibition of ERK mitogen activated protein kinase in traumatic brain injury. J Neurotrauma 19: 1411–1419
Nagase H, Woessner JF Jr (1999) Matrix metalloproteinases. J Biol Chem 274: 21491–21494
Romanic AM, White RF, Arleth AJ, Ohlstein EH, Barone FC (1998) Matrix metalloproteinase expression increases after cerebral focal ischemia in rats: inhibition of matrix metalloproteinase-9 reduces infarct size. Stroke 29: 1020–1030
Rosenberg GA, Navratil M, Barone F, Feuerstein G (1996) Proteolytic cascade enzymes increase in focal cerebral ischemia in rat. J Cereb Blood Flow Metab 16: 360–366
Uyama O, Okamura N, Yanase M, Narita M, Kawabata K, Sugita M (1988) Quantitative evaluation of vascular permeability in the gerbil brain after transient ischemia using Evans blue fluorescence. J Cereb Blood Flow Metab 8: 282–284
Vecil GG, Larsen PH, Corley SM, Herx LM, Besson A, Goodyer CG, Yong VW (2000) Interleukin-1 is a key regulator of matrix metalloproteinase-9 expression in human neurons in culture and following mouse brain trauma in vivo. J Neurosci Res 61: 212–224
Wang X, Jung J, Asahi M, Chwang W, Russo L, Moskowitz MA, Dixon CE, Fini ME, Lo EH (2000) Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury. J Neurosci 20: 7037–7042
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Shigemori, Y., Katayama, Y., Mori, T., Maeda, T., Kawamata, T. (2006). Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. In: Hoff, J.T., Keep, R.F., Xi, G., Hua, Y. (eds) Brain Edema XIII. Acta Neurochirurgica Supplementum, vol 96. Springer, Vienna. https://doi.org/10.1007/3-211-30714-1_29
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DOI: https://doi.org/10.1007/3-211-30714-1_29
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