Abstract
Traumatic brain injury (TBI) is a major cause of preventable death and serious morbidity, with subsequent low cerebral blood flow (CBF) considered to be associated with poor prognosis. In the present study, we demonstrated the effect of the free radical scavenger edaravone on regional CBF (rCBF) after TBI. Male mice (C57/BL6) were subjected to TBI using a controlled cortical impactor device. Immediately after TBI, the animals were intravenously administered 3.0 mg/kg of edaravone or a vehicle saline solution. Two-dimensional rCBF images were acquired before and 24 h post-TBI, and were quantified in the ipsilateral and contralateral hemispheres (n = 5 animals per group). CBF in the vehicle-treated animals decreased broadly over the ipsilateral hemisphere, with the region of low rCBF spreading from the frontal cortex to the occipital lobe. The zone of lowest rCBF matched that of the contusion area. The mean rCBF at 24 h for a defined elliptical region between the bregma and lambda was 73.7 ± 5.8 %. In comparison, the reduction of rCBF in edaravone-treated animals was significantly attenuated (93.4 ± 5.7 %, p < 0.05). The edaravone-treated animals also exhibited higher rCBF in the contralateral hemisphere compared with that seen in vehicle-treated animals. It is suggested that edaravone reduces neuronal damage by scavenging reactive oxygen species (ROS) and by maintaining intact the autoregulation of the cerebral vasculature.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alagarsamy S, DeWitt DS, Johnson KM (1998) Effects of moderate, central fluid percussion traumatic brain injury on nitric oxide synthase activity in rats. J Neurotrauma 15:627–633
Aoyama T, Hida K, Kuroda S, Seki T, Yano S, Shichinohe H, Iwasaki Y (2008) Edaravone (MCI-186) scavenges reactive oxygen species and ameliorates tissue damage in the murine spinal cord injury model. Neurol Med Chir (Tokyo) 48:539–545; discussion 545
Armstead WM, Kiessling JW, Kofke WA, Vavilala MS (2010) SNP improves cerebral hemodynamics during normotension but fails to prevent sex dependent impaired cerebral autoregulation during hypotension after brain injury. Brain Res 1330:142–150
Bouma GJ, Muizelaar JP, Bandoh K, Marmarou A (1992) Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. J Neurosurg 77:15–19
Bramlett HM, Dietrich WD (2004) Pathophysiology of cerebral ischemia and brain trauma: similarities and differences. J Cereb Blood Flow Metab 24:133–150
Brody DL, Mac Donald C, Kessens CC, Yuede C, Parsadanian M, Spinner M, Kim E, Schwetye KE, Holtzman DM, Bayly PV (2007) Electromagnetic controlled cortical impact device for precise, graded experimental traumatic brain injury. J Neurotrauma 24:657–673
Brown AW, Elovic EP, Kothari S, Flanagan SR, Kwasnica C (2008) Congenital and acquired brain injury. 1. Epidemiology, pathophysiology, prognostication, innovative treatments, and prevention. Arch Phys Med Rehabil 89:S3–S8
Bryan RM Jr, Cherian L, Robertson C (1995) Regional cerebral blood flow after controlled cortical impact injury in rats. Anesth Analg 80:687–695
Cherian L, Hlatky R, Robertson CS (2004) Nitric oxide in traumatic brain injury. Brain Pathol 14:195–201
Dohi K, Satoh K, Nakamachi T, Yofu S, Hiratsuka K, Nakamura S, Ohtaki H, Yoshikawa T, Shioda S, Aruga T (2007) Does edaravone (MCI- 186) act as an antioxidant and a neuroprotector in experimental traumatic brain injury? Antioxid Redox Signal 9:281–287
Fisher M (2008) Injuries to the vascular endothelium: vascular wall and endothelial dysfunction. Rev Neurol Dis 5(Suppl 1):S4–S11
Gahm C, Danilov A, Holmin S, Wiklund PN, Brundin L, Mathiesen T (2005) Reduced neuronal injury after treatment with NG-nitro-L-arginine methyl ester (L-NAME) or 2-sulfo-phenyl-N-tert-butyl nitrone (S-PBN) following experimental brain contusion. Neurosurgery 57:1272–1281; discussion 1272–1281
Hendrich KS, Kochanek PM, Williams DS, Schiding JK, Marion DW, Ho C (1999) Early perfusion after controlled cortical impact in rats: quantification by arterial spin-labeled MRI and the influence of spin-lattice relaxation time heterogeneity. Magn Reson Med 42:673–681
Hlatky R, Furuya Y, Valadka AB, Goodman JC, Robertson CS (2002) Comparison of microdialysate arginine and glutamate levels in severely head-injured patient. Acta Neurochir Suppl 81:347–349
Inokuchi Y, Imai S, Nakajima Y, Shimazawa M, Aihara M, Araie M, Hara H (2009) Edaravone, a free radical scavenger, protects against retinal damage in vitro and in vivo. J Pharmacol Exp Ther 329:687–698
Jitsuiki D, Higashi Y, Goto C, Kimura M, Noma K, Hara K, Nakagawa K, Oshima T, Chayama K, Yoshizumi M (2004) Effect of edaravone, a novel free radical scavenger, on endothelium-dependent vasodilation in smokers. Am J Cardiol 94:1070–1073
Lapchak PA (2010) A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy? Expert Opin Pharmacother 11:1753–1763
Lee BJ, Egi Y, van Leyen K, Lo EH, Arai K (2010) Edaravone, a free radical scavenger, protects components of the neurovascular unit against oxidative stress in vitro. Brain Res 1307:22–27
Liu H, Goodman JC, Robertson CS (2002) The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse. J Neurotrauma 19:327–334
Lukic-Panin V, Deguchi K, Yamashita T, Shang J, Zhang X, Tian F, Liu N, Kawai H, Matsuura T, Abe K (2010) Free radical scavenger edaravone administration protects against tissue plasminogen activator induced oxidative stress and blood brain barrier damage. Curr Neurovasc Res 7:319–329
Maeda T, Katayama Y, Kawamata T, Aoyama N, Mori T (1997) Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor. Acta Neurochir Suppl 70:102–105
Maeda T, Lee SM, Hovda DA (2005) Restoration of cerebral vasoreactivity by an L-type calcium channel blocker following fluid percussion brain injury. J Neurotrauma 22:763–771
Matsunaga M, Ohtaki H, Takaki A, Iwai Y, Yin L, Mizuguchi H, Miyake T, Usumi K, Shioda S (2003) Nucleoprotamine diet derived from salmon soft roe protects mouse hippocampal neurons from delayed cell death after transient forebrain ischemia. Neurosci Res 47:269–276
Matsushita Y, Bramlett HM, Kuluz JW, Alonso O, Dietrich WD (2001) Delayed hemorrhagic hypotension exacerbates the hemodynamic and histopathologic consequences of traumatic brain injury in rats. J Cereb Blood Flow Metab 21:847–856
Niiya Y, Abumiya T, Yamagishi SI, Takino JI, Takeuchi M (2012) Advanced glycation End products increase permeability of brain microvascular endothelial cells through reactive oxygen species-induced vascular endothelial growth factor expression. J Stroke Cerebrovasc Dis 21(4):293–298
Nilsson P, Gazelius B, Carlson H, Hillered L (1996) Continuous measurement of changes in regional cerebral blood flow following cortical compression contusion trauma in the rat. J Neurotrauma 13:201–207
Oyama J, Satoh S, Suematsu N, Kadokami T, Maeda T, Sugano M, Makino N (2010) Scavenging free radicals improves endothelial dysfunction in human coronary arteries in vivo. Heart Vessels 25:379–385
Ozawa Y, Nakamura T, Sunami K, Kubota M, Ito C, Murai H, Yamaura A, Makino H (1991) Study of regional cerebral blood flow in experimental head injury: changes following cerebral contusion and during spreading depression. Neurol Med Chir (Tokyo) 31:685–690
Pedersen MO, Larsen A, Stoltenberg M, Penkowa M (2009) Cell death in the injured brain: roles of metallothioneins. Prog Histochem Cytochem 44:1–27
Satoh K, Ikeda Y, Shioda S, Tobe T, Yoshikawa T (2002) Edarabone scavenges nitric oxide. Redox Rep 7:219–222
Sukmawan R, Yada T, Toyota E, Neishi Y, Kume T, Shinozaki Y, Mori H, Ogasawara Y, Kajiya F, Yoshida K (2007) Edaravone preserves coronary microvascular endothelial function after ischemia/reperfusion on the beating canine heart in vivo. J Pharmacol Sci 104:341–348
Sviri GE, Aaslid R, Douville CM, Moore A, Newell DW (2009) Time course for autoregulation recovery following severe traumatic brain injury. J Neurosurg 111:695–700
Wada K, Chatzipanteli K, Busto R, Dietrich WD (1999) Effects of L-NAME and 7-NI on NOS catalytic activity and behavioral outcome after traumatic brain injury in the rat. J Neurotrauma 16:203–212
Wang GH, Jiang ZL, Li YC, Li X, Shi H, Gao YQ, Vosler PS, Chen J (2011) Free-radical scavenger edaravone treatment confers neuroprotection against traumatic brain injury in rats. J Neurotrauma 28(10):2123–2134
Watanabe T, Yuki S, Egawa M, Nishi H (1994) Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. J Pharmacol Exp Ther 268:1597–1604
White H, Venkatesh B (2008) Cerebral perfusion pressure in neurotrauma: a review. Anesth Analg 107:979–988
Yagi K, Kitazato KT, Uno M, Tada Y, Kinouchi T, Shimada K, Nagahiro S (2009) Edaravone, a free radical scavenger, inhibits MMP-9-related brain hemorrhage in rats treated with tissue plasminogen activator. Stroke 40:626–631
Yamakami I, McIntosh TK (1991) Alterations in regional cerebral blood flow following brain injury in the rat. J Cereb Blood Flow Metab 11:655–660
Yamashita T, Deguchi K, Nagotani S, Abe K (2011) Vascular protection and restorative therapy in ischemic stroke. Cell Transplant 20:95–97
Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N (2006) Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev 12:9–20
Acknowledgments
The project was supported by a Grant-in-Aid for Young Scientists (Start-up) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (KM). This work was also supported in part by a grant from the Research on Health Sciences focusing on Drug Innovation program funded by The Japan Health Sciences Foundation (SS).
Conflict of InterestWe declare that we have no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Wien
About this paper
Cite this paper
Miyamoto, K. et al. (2013). Edaravone Increases Regional Cerebral Blood Flow After Traumatic Brain Injury in Mice. In: Katayama, Y., Maeda, T., Kuroiwa, T. (eds) Brain Edema XV. Acta Neurochirurgica Supplement, vol 118. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1434-6_18
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1434-6_18
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1433-9
Online ISBN: 978-3-7091-1434-6
eBook Packages: MedicineMedicine (R0)