Abstract
Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.
Highlights
IntroductionAbout 87% of patients with stroke are caused by ischemia, and ischemic stroke is induced by a loss of blood supply to part of the brain [3]
Stroke is developed due to ischemia and hemorrhage in the brain and it is the second leading global cause of death [1,2].About 87% of patients with stroke are caused by ischemia, and ischemic stroke is induced by a loss of blood supply to part of the brain [3]
It has been known that drugs, which show substantial efficacy in animal models of cerebral ischemia, could improve outcome in human stroke; rigorous experimental designs and statistical analyses in preclinical experiments are necessary to develop effective therapies in clinical patients [22]
Summary
About 87% of patients with stroke are caused by ischemia, and ischemic stroke is induced by a loss of blood supply to part of the brain [3]. ASA is known to be useful in the management of patients with cerebral ischemia, due to its anti-thrombotic as well as direct neuroprotective effect [9]. Focal cerebral ischemia was achieved by middle cerebral artery occlusion (MCAO) on the right-side (Belayev et al, 1996). A piece of 3-0monofilament nylon suture (Ethicon, Johnson-Johnson, Brussels, Belgium), with its tip rounded by gentle heating and coated by 0.1% (w/v) poly-L-lysine, was inserted into the lumen of right ECA stump and gently advanced 17.5 mm into the internal carotid artery (ICA) from the bifurcation to occlude the ostium of MCA. Sham-operated animals were subjected to the same surgical procedures except that the ICA were not inserted
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