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Protective effect of dl-3n-butylphthalide preconditioning on focal cerebral ischaemia-reperfusion injury in rats

Published online by Cambridge University Press:  22 February 2013

Pei-Lei Zhang ,
Hai-Tao Lu ,
Jun-Gong Zhao  and
Ming-Hua Li
Pei-Lei Zhang
Affiliation:
Department of Diagnostic and Interventinal Radiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, People's Republic of China
Hai-Tao Lu*
Affiliation:
Department of Diagnostic and Interventinal Radiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, People's Republic of China
Jun-Gong Zhao*
Affiliation:
Department of Diagnostic and Interventinal Radiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, People's Republic of China
Ming-Hua Li
Affiliation:
Department of Diagnostic and Interventinal Radiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, People's Republic of China
*
Hai-Tao Lu and Jun-Gong Zhao, Department of Diagnostic and Interventinal Radiololgy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yi Shan Rd, Shanghai 200233, People's Republic of China. Tel: +862164369181 (ext. 8016); Fax: +862164844183; E-mail: [email protected]; [email protected]
Hai-Tao Lu and Jun-Gong Zhao, Department of Diagnostic and Interventinal Radiololgy, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yi Shan Rd, Shanghai 200233, People's Republic of China. Tel: +862164369181 (ext. 8016); Fax: +862164844183; E-mail: [email protected]; [email protected]
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Abstract

Objective

To investigate the effect of dl-3n-butylphthalide (NBP) on the protection of cerebral tissue and possible mechanism on ischaemia-reperfusion injury, and to find out whether NBP therapy can extend the reperfusion window in an experimental stroke model in rats.

Methods

Seventy-two Sprague-Dawley rats were randomly divided into sham operation, ischaemia-reperfusion and ischaemia-reperfusion with NBP groups. Focal cerebral ischaemia was induced using the modified intraluminal thread method and maintained for 2, 3 or 4 h. The ischaemia-reperfusion group received reperfusion immediately after ischaemia-reperfusion. The NBP group received intraperitoneal injection of NBP immediately after ischaemia, followed by reperfusion. The sham operation group received only injection of physiological saline. The cerebral infarction volume and neurological deficit were analysed, and vascular endothelial growth factor (VEGF) expression in brain tissues was visualised by immunohistochemistry.

Results

NBP treatment caused a significant decrease in both infarction volume and neurological deficit compared with the ischaemia-reperfusion group at corresponding time points in each (p < 0.05). In the NBP group, the infarction volume and neurological deficit did not change with different ischaemia times. The expression of VEGF was significantly decreased in the ischaemia-reperfusion group compared with the sham group (p < 0.01), while this change was partly prevented in the NBP group (p < 0.01). The expression of VEGF in brain tissue in both the NBP and ischaemia-reperfusion groups gradually decreased when the ischaemic period was prolonged.

Conclusion

NBP treatment has a protective effect against cerebral ischaemia; this possible mechanism maybe related to the VEGF expression and may extend the reperfusion window for subsequent salvage of cerebral ischaemia by reperfusion.

Keywords

cerebral ischaemiadl-3n-butylphthalideneuroprotectionratsreperfusion injuryvascular endothelial growth factor
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 25 , Issue 1 , February 2013 , pp. 12 - 17
Copyright
Scandinavian College of Neuropsychopharmacology 2013

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References

1Huang, C, Xia, PY, Zhou, H.Sustained expression of TDP-43 and FUS in motor neurons in rodent's lifetime. Int J Biol Sci 2010;6:396–406.CrossRefGoogle ScholarPubMed
2Srivastava, A, Taly, AB, Gupta, Aet al.Stroke with supernumerary phantom limb: case study, review of literature and pathogenesis. Acta Neuropsychiatrica 2008;20: 256–264.Google Scholar
3Zhang, Y, Wang, L, Li, J, Wang, XL.2-(1-Hydroxy Pentyl)-benzoate increase cerebral blood flow and reduces infarct volume in rats model of transient focal cerebral ischemia. J Pharmacol Exp Ther 2006;317:973–979.Google Scholar
4Liu, CL, Liao, SJ, Zeng, JSet al.Dl-3n-butylphthalide prevents stroke via improvement of cerebral microvessels in RHRSP. J Neurol Sci 2007;260:106–113.Google Scholar
5Liao, SJ, Lin, JW, Pei, Z, Liu, CL, Zeng, JS, Huang, RX.Enhanced angiogenesis with dl-3n-butylphthalide treatment after focal cerebral ischemia in RHRSP. Brain Res 2009;1289:69–78.CrossRefGoogle ScholarPubMed
6Schmidt, NO, Koeder, D, Messing, Met al.Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. Brain Res 2009;1268:24–37.Google Scholar
7Longa, EZ, Weinstein, PR, Carlson, S, Cummins, R.Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 1989;20:84–91.CrossRefGoogle ScholarPubMed
8Nam, KN, Choi, YS, Jung, HJet al.Genipin inhibits the inflammatory response of rat brain microglial cells. Int Immunopharmacol 2010;10:493–499.Google Scholar
9Chong, ZZ, Feng, YP.Effects of dl-3-n-butylphthalide on production of TXB2 and 6-keto-PGF1 alpha in rat brain during focal cerebral ischemia and reperfusion. Acta Pharmacol Sin 1997;18:505–508.Google ScholarPubMed
10Dong, GX, Feng, YP.Effects of NBP on ATPase and anti-oxidant enzymes activities and lipid peroxidation in transient focal cerebral ischemic rats. Acta Acad Med Sin 2002;24:93–97.Google Scholar
11Graf, R.Letter of apology. Cerebral ischemia and reperfusion: the pathophysiologic concept as a basis for clinical therapy. J Cereb Blood Flow Metab 2005;25:291.Google Scholar
12Shi, H, Liu, KJ.Cerebral tissue oxygenation and oxidative brain injury during ischemia and reperfusion. Front Biosci 2007;12:1318–1328.Google Scholar
13Sims, NR, Muyderman, H.Mitochondria, oxidative metabolism and cell death in stroke. Biochim Biophys Acta 2009;1802:80–91.CrossRefGoogle ScholarPubMed
14The European Cooperative Acute Stroke Study (ECASS). Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359:1317–1329.Google Scholar
15Chen, YH, Wu, HL, Chen, CKet al.Angiostatin antagonizes the action of VEGF-A in human endothelial cells via two distinct pathways. Biochem Biophys Res Commun 2003;310:804–810.Google Scholar
16Jin, K, Mao, XO, Greenberg, DA.Vascular endothelial growth factor stimulates neurite outgrowth from cerebral cortical neurons via Rho kinase signaling. J Neurobio 2006;66:236–242.Google Scholar
17Yasuhara, T, Shingo, T, Kobayashi, Ket al.Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of Parkinson's disease. Eur J Neurosci 2004;19:1494–1504.Google Scholar
18Rosenstein, JM, Krum, JM.New roles for VEGF in nervous tissue–beyond blood vessels. Exp Neurol 2004;187: 246–253.Google Scholar
19Lennmyr, F, Ata, KA, Funa, K, Olsson, Y, Terent, A.Expression of vascular endothelial growth factor (VEGF) and its receptors (Flt-1 and Flk-1) following permanent and transient occlusion of the middle cerebral artery in the rat. J Neuropathol Exp Neurol 1998;57:874–882.Google Scholar