Erik M. Loria; Cristina Schroeder; Polly Wallis; Michael B. Prendini
Abstract
Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID), and little is known regarding the effect of Meloxicam in acute cerebral ischemia. Here, we designed this study to investigate the potential protective effects of Meloxicam in cerebral ischemia induced by 60-minute of middle cerebral artery occlusion (MCAO) followed by reperfusion cell injury for 24-hr. C57Bl6/N mice were pretreated with Meloxicam or normal saline (control). Infarct volumes were determined using magnetic resonance imaging and tetrazolium staining. Immunofluorescence was performed to evaluate apoptosis of neuron cells. The expression levels of proinflammatory cytokines and PI3K/Akt pathway were detected by ELISA and Western blot respectively. The results showed that Meloxicam decreased cerebral ischemia, improved neurological function and attenuated cellular apoptosis in vascular endothelial cell. These findings suggest that Meloxicam may play a major role in neruoprotective following transient focal cerebral ischemia and further studies will elucidate the effect of Meloxicam treatment on cell proliferation and behavioral outcome in moderate to severe ischemic injury in the brain.
Keywords: Meloxicam; Cerebral ischemia; Stroke; MCAO
You will have online immediate access to article following the completion of this purchase and you may download and print a copy of each article for your personal use.
References
1. Stoll G, Kleinschnitz C, Nieswandt B. Combating innate inflammation: a new paradigm for acute treatment of stroke? Ann N Y Acad Sci 2010; 1207: 149–154. [PubMed]
2. Salomon JA, Wang H, Freeman MK, Vos T, Flaxman, AD, Lopez AD, Murray CJ. The global burden of disease study 2010. Lancet 2013; 380:2053–2260. [Abstract/Full-Text]
2. Becker KJ. Modulation of the postischemic immune response to improve stroke outcome. Stroke 2010; 41: S75–78. [PubMed]
3. Molin C, Montaner J, Abilleira S, Romero F, Ibarra B, Arenillas JF, Álvarez Sabín J. Timing of spontaneous recanalization and risk of hemorrhagic transformation in acute cardioembolic stroke. Stroke 2001; 32: 1079–1084. [Abstract/Full-Text]
4. Eltzschig HK, Eckle T. Ischemia and reperfusion – from mechanism to translation. Nat Med 2011; 17:1391-1401.
5. Iadecola C, Alexander M. Cerebral ischemia and inflammation. Curr Opin Neurol 2001; 14:89-94.
6. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke 2009, 40:e331-e339.
7. Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology 2008; 55:310-318.
8. Xu M, Zhang HL. Death and survival of neuronal and astrocytic cells in ischemic brain injury: A role of autophagy. Acta Pharmacol. Sin 2011; 32:1089–1099. [Google Scholar]
9. Broughton BR, Reutens DC, Sobey CG. Apoptotic mechanisms after cerebral ischemia. Stroke 2009; 40: e331–e339. [Google Scholar]
10. Carloni S. Buonocore G, Balduini W. Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis 2008; 32:329–339. [Abstract/Full-Text]
11. Meloxicam official FDA information, side effects, and uses". Drugs.com. March 2010. Retrieved 17 March 2010. [Website]
12. Noble S, Balfour JA. Meloxicam. Drugs 1996; 51(3): 424–30. [PubMed]
13. Eltzschig HK, Eckle T. Ischemia and reperfusion-from mechanism to translation. Nature Medicine 2011; 11:1391–1401.
14. Kaczorowski DJ, Mollen K P, Edmonds R, Billiar TR. Early events in the recognition of danger signals after tissue injury. Journal of Leukocyte Biology 2008; 83:546–552.
15. Becker KJ. Modulation of the postischemic immune response to improve stroke outcome. Stroke 2010; 41:S75–78.
16. Choe CU, Lewerenz J, Fischer G, et al. Nitroxyl exacerbates ischemic cerebral injury and oxidative neurotoxicity. J Neurochem 2009; 110:1766–1773. [PubMed]
17. Gelderblom M, Leypoldt F, Steinbach K, et al. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke 2009; 40:1849–1857. [PubMed]
18. Longa EZ, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989; 20:84-91. [PubMed]
19. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986; 17:472-476. [PubMed]
20. Yousif NG, Al-Amran FG. Novel Toll-like receptor-4 deficiency attenuates trastuzumab (Herceptin) induced cardiac injury in mice. BMC Cardiovasc Disord 2011; 11:62. [PubMed]
21. Dirnagl U, Iadecola C, Moskowitz MA. Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 1999; 22:391–397. [PubMed]
22. Krams M, Lees KR, Hacke W, Grieve AP, Orgogozo JM, Ford GA. Acute stroke therapy by inhibition of neutrophils (ASTIN): an adaptive dose-response study of UK-279,276 in acute ischemic stroke. Stroke 2003; 34:2543–2548. [PubMed]
23. Bhaskar PT, Hay N. The two TORCs and Akt. Dev. Cell 2007; 12(4):487–502.
24. Brugge J, Hung MC, Mills GB. A new mutational AKTivation in the PI3K pathway. Cancer Cell 2007; 12(2):104–7.
