J Cerebrovasc Endovasc Neurosurg.  2013 Sep;15(3):171-176. 10.7461/jcen.2013.15.3.171.

The Role of Adiponectin in Secondary Inflammatory Reaction in Cerebral Ischemia

Affiliations
  • 1Department of Neurosurgery, Korea University Ansan Hospital, School of Medicine, Korea University, Ansan, Korea. sungkha@yahoo.com

Abstract


OBJECTIVE
In this study, we investigate the role of adiponectin in the interaction between leukocytes and endothelium in the secondary inflammatory reaction of cerebral ischemia.
METHODS
Adiponectin knock-out mice group (APN-KO) (n = 8) and wild-type mice group (WT) (n = 8) were prepared. Each group was sub-divided into 2 groups by reperfusion time. One-hour middle cerebral artery occlusion and reperfusion were induced using the intraluminal filament technique. At 6 and 12 hours after the occlusion, the mice were placed on a stereotactic frame to perform craniotomy in the left parietal area. After craniotomy, a straight pial venule was selected as a target vessel. With the fluorescence intravital microscope, the number of rolling leukocytes and leukocytes that adhered to endothelium were counted and documented at 6 and 12 hours after the reperfusion.
RESULTS
At 6 and 12 hours after the reperfusion, more rolling leukocyte and leukocyte adhesion were observed in the APN-KO mice than in the WT mice. The difference in leukocyte numbers between the APN-KO and WT mice was found to be statistically significant (p = 0.029) by Mann-Whitney U-test.
CONCLUSION
We found that adiponectin inhibits the interaction between the endothelium and leukocytes in cerebral ischemia-reperfusion. Therefore adiponectin might prevent the secondary insult caused by the inflammation reaction.

Keyword

Adiponectin; Cerebral ischemia; Secondary inflammatory reaction; MCAO-R

MeSH Terms

Adiponectin
Animals
Brain Ischemia
Craniotomy
Endothelium
Fluorescence
Glycosaminoglycans
Infarction, Middle Cerebral Artery
Inflammation
Leukocyte Count
Leukocytes
Mice
Mice, Knockout
Reperfusion
Venules
Adiponectin
Glycosaminoglycans

Figure

  • Fig. 1 Representative image of intraluminal filament technique. Silicon-coated 8-0 monofilament is directed to the middle cerebral artery through the common carotid artery.

  • Fig. 2 Representative image of cranial window preparation. After performing 4×6 mm-sized craniotomy in the left parietal area using a dental drill.

  • Fig. 3 Representative images of rhodamine-labeled leukocytes in venules. (A) 6hWT, (B) 6hKO, (C) 12hWT, (D) 12hKO (Single arrow: rolling leukocyte, blank arrow: leukocyte aggregate). 6hWT: Wild-type mice at 6 hours of reperfusion, 6hKO: Adiponectin-deficient mice at 6 hours of reperfusion, 12hWT: Wild-type mice at 12 hours of reperfusion, 12hKO: Adiponectin-deficient mice at 12 hours of reperfusion.

  • Fig. 4 Comparison of the experimental groups at 6 hours and 12 hours after ischemia. The difference in leukocyte number between the APN-KO and WT mice at 6, 12 hours after the occlusion was statistically significant (Mann-Whitney U-test, p value = 0.029).


Reference

1. Bang OY, Saver JL, Ovbiagele B, Choi YJ, Yoon SR, Lee KH. Adiponectin levels in patients with intracranial atherosclerosis. Neurology. 2007; 5. 68(22):1931–1937. PMID: 17536050.
Article
2. Barone FC, Hillegass LM, Price WJ, White RF, Lee EV, Feuerstein GZ, et al. Polymorphonuclear leukocyte infiltration into cerebral focal ischemic tissue: Myeloperoxidase activity assay and histologic verification. J Neurosci Res. 1991; 7. 29(3):336–345. PMID: 1656059.
Article
3. Chen H, Chopp M, Zhang RL, Bodzin G, Chen Q, Rusche JR, et al. Anti-CD11b monoclonal antibody reduces ischemic cell damage after transient focal cerebral ischemia in rat. Ann Neurol. 1994; 4. 35(4):458–463. PMID: 8154873.
Article
4. Chen MP, Tsai JC, Chung FM, Yang SS, Hsing LL, Shin SJ, et al. Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler Thromb Vasc Biol. 2005; 4. 25(4):821–826. PMID: 15692106.
Article
5. Chopp M, Zhang RL, Chen H, Li Y, Jiang N, Rusche JR. Postischemic administration of an anti-Mac-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in rats. Stroke. 1994; 4. 25(4):869–875. discussion 875-6. PMID: 8160235.
Article
6. Efstathiou SP, Tsioulos DI, Tsiakou AG, Gratsias YE, Pefanis AV, Mountokalakis TD. Plasma adiponectin levels and five-year survival after first-ever ischemic stroke. Stroke. 2005; 9. 36(9):1915–1919. PMID: 16109902.
Article
7. Grau AJ, Graf T, Hacke W. Altered influence of polymorphonuclear leukocytes on coagulation in acute ischemic stroke. Thromb Res. 1994; 12. 76(6):541–549. PMID: 7900101.
Article
8. Grøgaard B, Schurer L, Gerdin B, Arfors KE. Delayed hypoperfusion after incomplete forebrain ischemia in the rat. The role of polymorphonuclear leukocytes. J Cereb Blood Flow Metab. 1989; 8. 9(4):500–505. PMID: 2738115.
Article
9. Hallenbeck JM. Significance of the inflammatory response in brain ischemia. Acta Neurochir Suppl. 1996; 66:27–31. PMID: 8780793.
Article
10. Hallenbeck JM, Dutka AJ, Tanishima T, Kochanek PM, Kumaroo KK, Thompson CB, et al. Polymorphonuclear leukocyte accumulation in brain regions with low blood flow during the early postischemic period. Stroke. 1986; Mar-Apr. 17(2):246–253. PMID: 3961835.
Article
11. Hara H, Friedlander RM, Gagliardini V, Ayata C, Fink K, Huang Z, et al. Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage. Proc Natl Acad Sci U S A. 1997; 3. 94(5):2007–2012. PMID: 9050895.
12. Matsuo Y, Kihara T, Ikeda M, Ninomiya M, Onodera H, Kogure K. Role of neutrophils in radical production during ischemia and reperfusion of the rat brain: Effect of neutrophil depletion on extracellular ascorbyl radical formation. J Cereb Blood Flow Metab. 1995; 11. 15(6):941–947. PMID: 7593354.
Article
13. Matsuo Y, Onodera H, Shiga Y, Shozuhara H, Ninomiya M, Kihara T, et al. Role of cell adhesion molecules in brain injury after transient middle cerebral artery occlusion in the rat. Brain Res. 1994; 9. 656(2):344–352. PMID: 7820595.
Article
14. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004; 1. 24(1):29–33. PMID: 14551151.
Article
15. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 11. 106(22):2767–2770. PMID: 12451000.
Article
16. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: Adipocyte-derived plasma protein adiponectin. Circulation. 1999; 12. 100(25):2473–2476. PMID: 10604883.
17. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol. 2003; 12. 14(6):561–566. PMID: 14624132.
Article
18. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004; 12. 10(12):1384–1389. PMID: 15558058.
Article
19. Shibata R, Ouchi N, Kihara S, Sato K, Funahashi T, Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004; 7. 279(27):28670–28674. PMID: 15123726.
Article
20. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005; 10. 11(10):1096–1103. PMID: 16155579.
Article
21. Suzuki H, Abe K, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, et al. Reduction of ischemic brain injury by anti-P-selectin monoclonal antibody after permanent middle cerebral artery occlusion in rat. Neurol Res. 1999; 4. 21(3):269–276. PMID: 10319335.
Article
22. Tao L, Jiao X, Gao E, Lau WB, Yuan Y, Lopez B, et al. Nitrative inactivation of thioredoxin-1 and its role in postischemic myocardial apoptosis. Circulation. 2006; 9. 114(13):1395–1402. PMID: 16966583.
Article
23. Vasthare US, Heinel LA, Rosenwasser RH, Tuma RF. Leukocyte involvement in cerebral ischemia and reperfusion injury. Surg Neurol. 1990; 4. 33(4):261–265. PMID: 2326731.
Article
24. Yatomi K, Miyamoto N, Komine-Kobayashi M, Liu M, Oishi H, Arai H, et al. Pathophysiological dual action of adiponectin after transient focal ischemia in mouse brain. Brain Res. 2009; 11. 1297:169–176. PMID: 19699724.
Article
25. Zhang RL, Chopp M, Jiang N, Tang WX, Prostak J, Manning AM, et al. Anti-intercellular adhesion molecule-1 antibody reduces ischemic cell damage after transient but not permanent middle cerebral artery occlusion in the Wistar rat. Stroke. 1995; 8. 26(8):1438–1442. discussion 1443. PMID: 7631350.
Article
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