Local cerebral glucose utilisation following acute and chronic bilateral carotid artery ligation in Wistar rats: relation to changes in local cerebral blood flow

Cho

Korean J Physiol Pharmacol

2008

In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging and Alzheimer's disease, we introduced permanent, bilateral occlusion of the common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced BCCAO in two different rat strains in order to determine whether there was a strain difference in the pathogenic response to BCCAO. Male W istar and Sprague-Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Klüver-Barrera and cresyl violet staining were used to evaluate white matter and gray matter damage, respectively. W istar rats had a considerably higher mortality rate (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO. Complete loss of pupillary light reflex occurred in all Wistar rats that survived, but loss of pupillary light reflex did not occur at all in SD rats. Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons than W istar rats following BCCAO. These results suggest that the neuropathological process induced by BCCAO takes place in a region-specific pattern that varies according to the strain of rat involved.

Section: Introductionmentioning

confidence: 99%

White Matter Damage and Hippocampal Neurodegeneration Induced by Permanent Bilateral Occlusion of Common Carotid Artery in the Rat: Comparison between Wistar and Sprague-Dawley Strain

Cho

Korean J Physiol Pharmacol

2008

“…As well, the decrease in cerebral blood flow relates to the cognitive impairment seen in AD (Kasparova et al, 2005). Bilateral permanent occlusion of the common carotid arteries (BCCAO) in rats results in a significant reduction in cerebral blood flow; therefore, it is a useful model of chronic cerebral hypoperfusion (Tsuchiya et al, 1993). This animal model exhibits learning and memory impairments resembling those found in AD and VaD, accompanied by neuronal degeneration and microvascular abnormalities (Farkas et al, 2004).…”

mentioning

confidence: 99%

“…1 week of BCCAO (Tsuchiya et al, 1993). These regions include the cortex and hippocampus, which among other regions play important roles in learning and memory (Tsuchiya et al, 1993).…”

mentioning

confidence: 99%

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l-3-n-Butylphthalide Improves Cognitive Impairment Induced by Chronic Cerebral Hypoperfusion in Rats

Peng¹,

Xu²,

Chen³

et al. 2007

J Pharmacol Exp Ther

3-n-Butylphthalide (NBP) may be beneficial for the treatment of ischemic stroke with multiple actions on different pathophysiological processes. In the present study, we investigated the effect of NBP isomers on learning and memory impairment induced by chronic cerebral hypoperfusion in rats. Male Wistar rats were orally administered 10 and 30 mg/kg l-, d-, or dl-NBP daily for 23 days after bilateral permanent occlusion of the common carotid arteries. Rats receiving 10 mg/kg l-NBP performed significantly better in tests for spatial learning and memory, and they had attenuated cerebral pathology, including neuronal damage, white matter rarefaction, and glial activation compared with controls. Furthermore, 10 mg/kg l-NBP-treated rats had significantly higher choline acetyltransferase activity, decreased cortical lipid peroxide, and reduced hippocampal superoxide dismutase activity, compared with vehicle controls. However, d-and dl-NBP did not show significant beneficial effects. The present findings demonstrate that the beneficial effects of l-NBP on hypoperfusion-induced cognitive deficits may be due to preventing neuropathological alterations, inhibiting oxidative damage and increasing acetylcholine synthesis. Our results strongly suggest that l-NBP has therapeutic potential for the treatment of dementia caused by decreased cerebral blood flow.Senile dementia, a progressive aging-related disease, has become an important medical and social problem due to the increase in the number of elderly. Vascular dementia (VaD), as the second most common form of dementia in the elderly, accounts for approximately 20 to 30% of dementia cases (Giacobini, 2004). VaD is a syndrome presenting with both cognitive and noncognitive symptoms. Cognitive deficits of VaD include memory deficits, executive function damage, slow processing of information, and behavioral and mood abnormalities (Micieli, 2006). The underlying basis of VaD is complicated, because cerebral multi-infarct, cerebrovascular diseases, arterial hypotension, cardiac arrest, and hemorrhagic diseases may all result in VaD (Micieli, 2006). At present, no specific drug exists to prevent, delay, or cure VaD.It is well known that a decrease in cerebral blood flow precedes the onset of VaD (Roman et al., 1993), and chronic cerebral hypoperfusion may be a trigger for VaD and the accompanying cognitive deficits (Kasparova et al., 2005). As well, the decrease in cerebral blood flow relates to the cognitive impairment seen in AD (Kasparova et al., 2005). Bilateral permanent occlusion of the common carotid arteries (BCCAO) in rats results in a significant reduction in cerebral blood flow; therefore, it is a useful model of chronic cerebral hypoperfusion (Tsuchiya et al., 1993). This animal model exhibits learning and memory impairments resembling those found in AD and VaD, accompanied by neuronal degeneration and microvascular abnormalities (Farkas et al., 2004).It has been widely accepted that chronic cerebral hypoperfusion induces oxidative stress damage and brain en...

Japanese Journal of Pharmacology

“…Permanent or transient bilateral occlusion of common carotid arteries in the rat is a model for whole brain ischemia and the local cerebral blood flow in anatomically discrete regions reportedly decreases to 25-8707o of the sham control at 2.5 hr after permanent occlusion of com mon carotid arteries (2VO) (3). We previously showed that 2VO caused impairment of spatial acquisition in a conventional 8-arm radial maze task and that this impair ment became more marked 1 to 4 months after the 2VO operation (4,5).…”

mentioning

confidence: 99%

Tacrine Improves Working Memory Deficit Caused by Permanent Occlusion of Bilateral Common Carotid Arteries in Rats

Murakami

Tanaka

Sakai

et al. 1997

ABSTRACT-Effect of tacrine, a cholinesterase inhibitor, on spatial acquisition deficit caused by perma nent occlusion of bilateral common carotid arteries (2VO) was examined by using the conventional 8-arm and the 4-arm baited radial maze tasks in rats. Daily administration of tacrine (0.1 and 0.3 mg/kg, i.p.) 1 month after 2VO operation significantly improved the impaired spatial acquisition in the conventional maze task. This treatment also ameliorated the 2VO-induced working but not reference memory deficit in the 4 arm baited radial maze task. These results suggest that tacrine improvement of working memory deficit in the 2VO rats is due to stimulation of central cholinergic systems.Keywords: Permanent occlusion of bilateral common carotid arteries, Spatial acquisition, TacrineA variety of animal models have been used to inves tigate the behavioral and pathophysiological changes observed in human dementia (1, 2) and to pharmaco logically elucidate activities of putative anti-amnesiac drugs. Although it is generally accepted that progressive cognitive dysfunction occurs in human dementia, cogni tive deficits observed in these animal models are usually transient and recover to a normal level in a time-depend ent manner.Permanent or transient bilateral occlusion of common carotid arteries in the rat is a model for whole brain ischemia and the local cerebral blood flow in anatomically discrete regions reportedly decreases to 25-8707o of the sham control at 2.5 hr after permanent occlusion of com mon carotid arteries (2VO) (3). We previously showed that 2VO caused impairment of spatial acquisition in a conventional 8-arm radial maze task and that this impair ment became more marked 1 to 4 months after the 2VO operation (4, 5). Besides these behavioral changes, the 2VO rats exhibited progressive neuronal degeneration and decrease in acetylcholine contents in the brain. Tanaka et al. (6) reported that muscarinic receptor binding ability decreased in 2VO rats. This muscarinic receptor dysfunction appeared to be correlated with discrimina tion learning disabilities of these animals. Thus, it is likely that changes in the function of central cholinergic systems caused by 2VO are involved in the impairment of learning and memory. In the present study, we examined the effect of tacrine, a cholinesterase inhibitor, on 2VO-induced impairment of spatial acquisition using conventional 8 arm and 4-arm baited radial maze tasks to test whether stimulation of cholinergic systems could improve the learning and memory deficits caused by 2VO.Male Wistar rats (Japan SLC Inc., Shizuoka) were housed in groups of four per cage in the laboratory animal room maintained at 25 ± 1 C with 65 ± 5 % humid ity on a 12 hr light/dark cycle (lights on: 07:30 to 19:30). The animals, at the age of 13 weeks, were anesthetized with sodium pentobarbital (45 mg/kg, i.p.), and bilateral common carotid arteries were ligated with silk thread