Subscribe to RSS
DOI: 10.1055/s-0028-1087210
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Aspirin Attenuates Cerebral Ischemic Injury in Diabetic Rats
Publication History
received 15.08.2008
first decision 05.09.2008
accepted 12.09.2008
Publication Date:
03 December 2008 (online)
Abstract
Diabetes is an independent risk factor for ischemic stroke. Large randomized trials have shown that aspirin reduces stroke risks in patients with diabetes. However, there was no study that reported whether aspirin could attenuate the cerebral ischemic injury when administered prior to cerebral ischemia in diabetes. The objective of the present study was to evaluate the effects of aspirin on focal cerebral ischemia in diabetic rats. Diabetic rats received an oral administration of aspirin for 7 d prior to be subjected to a permanent middle cerebral artery occlusion (MCAO). The infarct volume of the brain was assessed in brain slices stained with 2% solution of triphenyltetrazolium chloride. Behavioral tests were used to evaluate the damage to the central nervous system. Platelet aggregation induced by adenosine diphosphate was measured. The results showed that aspirin at a dose of 30 mg/kg but not 10 mg/kg significantly reduced infarct volume and decreased neurological deficit scores compared with vehicle treatment. Aspirin (30 mg/kg) treatment also reduced platelet aggregation. Administration of aspirin did not alter the levels of blood glucose and insulin in diabetic rats. The findings suggest that pretreatment with aspirin may be effective to attenuate cerebral ischemic injury in diabetic patients.
Key words
aspirin - diabetes - cerebral ischemia
References
- 1 Berger L, Hakim AM. The association of hyperglycemia with cerebral edema in stroke. Stroke. 1986; 17 865-871
- 2 Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999; 48 1-9
- 3 Colwell JA. American Diabetes Association . Aspirin therapy in diabetes. Diabetes Care. 2004; 27 S72-S73
- 4 Colwell JA, Nesto RW. The platelet in diabetes: focus on prevention of ischemic events. Diabetes Care. 2003; 26 2181-2188
- 5 Cosentino F, Assenza GE. Diabetes and inflammation. Herz. 2004; 29 749-759
- 6 Duckrow RB, Beard DC, Brennan RW. Regional cerebral blood flow decreases during hyperglycemia. Ann Neurol. 1985; 17 267-272
- 7 Cristóbal J De, Moro MA, Dávalos A. et al . Neuroprotective effect of aspirin by inhibition of glutamate release after permanent focal cerebral ischaemia in rats. J Neurochem. 2001; 79 456-459
- 8 Fukuoka S, Yeh H, Mandybur TI. et al . Effect of insulin on acute experimental cerebral ischemia in gerbils. Stroke. 1989; 20 396-399
- 9 Folbergrová J, Memezawa H, Smith ML. et al . Focal and perifocal changes in tissue energy state during middle cerebral artery occlusion in normo- and hyperglycemic rats. J Cereb Blood Flow Metab. 1992; 12 25-33
- 10 Grilli M, Pizzi M, Memo M. et al . Neuroprotection by aspirin and sodium salicylate through blockade of NF-kappaB activation. Science. 1996; 274 1383-1385
- 11 Idris I, Gray S, Donnelly R. Protein kinase C activation: isozyme-specific effects on metabolism and cardiovascular complications in diabetes. Diabetologia. 2001; 44 659-673
- 12 Kuhn W, Müller T, Bttner T. et al . Aspirin as a free radical scavenger: consequences for therapy of cerebrovascular ischemia. Stroke. 1995; 26 1959-1960
- 13 Longa EZ, Weinstein PR, Carlson S. et al . Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989; 20 84-91
- 14 Li PA, Shuaib A, Miyashita H. et al . Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia. Stroke. 2000; 31 183-192
- 15 Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study. Lancet. 1997; 349 1269-1276
- 16 Oppenheimer SM, Hoffbrand BI, Oswald GA. et al . Diabetes mellitus and early mortality from stroke. Br Med J. 1985; 291 1014-1015
- 17 Olsson T, Viitanen M, Asplund K. et al . Prognosis after stroke in diabetic patients. A controlled prospective study. Diabetologia. 1990; 33 244-249
- 18 Rosamond WD, Folsom AR, Chambless LE. et al . Stroke incidence and survival among middle-aged adults: 9-year follow-up of the atherosclerosis risk in communities (ARIC) cohort. Stroke. 1999; 30 736-743
- 19 Sprafka JM, Virnig BA, Shahar E. et al . Trends in diabetes prevalence among stroke patients and the effect of diabetes on stroke survival: the Minnesota heart survey. Diabet Med. 1994; 11 678-684
- 20 Schmidt AM, Yan SD, Wautier JL. et al . Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res. 1999; 84 489-497
- 21 Tuomilehto J, Rastenyte D, Jousilahti P. et al . Diabetes mellitus as a risk factor for death from stroke. Prospective study of the middle-aged Finnish population. Stroke. 1996; 27 210-215
- 22 Voll CL, Auer RN. Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. J Cereb Blood Flow Metab. 1991; 11 1006-1014
- 23 Yorek MA. The role of oxidative stress in diabetic vascular and neural disease. Free Radic Res. 2003; 37 471-480
Correspondence
Prof. F. H. Fu
School of Pharmacy
Yantai University
Yantai Shandong 264005
China
Phone: +86/535/670 60 60
Fax: +86/535/670 60 66
Email: fufenghua@sohu.com