Abstract
Astragaloside IV (AS-IV) has been reported to have a prominent antioxidant effect and was proposed as a promising agent for the prevention of neurodegenerative disorders accompanied by cognitive impairment. The present study investigated the ameliorating effect of AS-IV on learning and memory deficits induced by chronic cerebral hypoperfusion in rats. Rats were treated with two doses of AS-IV (10 and 20 mg/kg, i.p.) daily for 28 days starting from the 5th week after permanent bilateral common carotid artery occlusion. AS-IV treatment (at dose of 20 mg/kg) significantly improved the spatial learning and memory deficits assessed using the Morris water maze test in rats with chronic cerebral hypoperfusion. AS-IV significantly attenuated neuronal apoptosis as well as the levels of superoxide dismutase and lipid peroxidation markers, including malondialdehyde and 4-hydroxy-2-nonenal, in the hippocampus. AS-IV also significantly reduced 8-hydroxy-2’-deoxyguanosine expression, a maker of oxidative DNA damage, while significantly inhibited the astrocyte and microglia activation in the hippocampus. The results indicate that AS-IV has therapeutic potential for the prevention of dementia caused by cerebral hypoperfusion and suggest that the ameliorating effect of AS-IV on learning and memory deficits might be the result of suppressing neuronal apoptosis and oxidative damage in the hippocampus.
Highlights
Cerebral hypoperfusion is associated with impaired cognitive functions both in Alzheimer’s disease (AD) and vascular dementia (VaD), which are the more common causes of cognitive impairment in aging
The permanent bilateral common carotid artery occlusion (pBCAO) in rats is the most common method to investigate the effects of chronic cerebral hypoperfusion on cognitive dysfunction and neurodegenerative processes
After the pBCAO in rats, the cerebral blood flow (CBF) in the cerebral cortex and white matter areas was recorded to ~35%–45% of the control level, the CBF in the hippocampus decreasing to a lesser extent to ~60% of the control [20,21]
Summary
Cerebral hypoperfusion is associated with impaired cognitive functions both in Alzheimer’s disease (AD) and vascular dementia (VaD), which are the more common causes of cognitive impairment in aging. Oxidative stress of vascular origin as a result of chronic cerebrovascular hypoperfusion plays a significant role in the onset and progression of neurodegenerative diseases [4]. Oxidative stress and oxidative DNA damage are important factors involved in the pathogenesis of mixed AD and VaD [7] These suggest that treating patients with antioxidants may prevent and delay the progression of the disease. Under the hypothesis that the antioxidant and anti-apoptotic properties of AS-IV will exert influence on ameliorating learning and memory impairments, the present study investigated the effect of AS-IV in chronic cerebral hypoperfusion model of rats induced by permanent bilateral common carotid artery occlusion (pBCAO). We demonstrated that AS-IV improved learning and memory deficits via inhibiting oxidative damage, neuronal apoptosis, and glial activation in the hippocampus after chronic cerebral hypoperfusion
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