Animal Models of Vascular Dementia With Emphasis on Stroke‐prone Spontaneously Hypertensive Rats

Saito, Hideya; Togashi, Hiroko; Yoshioka, Mitsuhiro; Nakamura, Nishio; Minami, Masaru; Parvez, H.

doi:10.1111/j.1440-1681.1995.tb02906.x

Cited by 56 publications

(27 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SHRSP is an animal model of human cerebrovascular disease: as in the case of humans, these rats exhibit severe hypertension and spontaneously occurring strokes (Okamoto et al, 1974, Yamori et al, 1976, Saito et al, 1995, Sakurai-Yamashita et al, 1997, Qiang et al, 1989. It was found that in SHRSPs, DND was induced in the CA1 subfield of the hippocampus by transient occlusion of the carotid arteries, i.e., 2-VO (Yamashita et al, 1993, Qiang et al, 1989, although in normotensive rats, DND was induced by transient occlusion of the carotid arteries following the permanent occlusion of the vertebral arteries, i.e., 4-VO and not 2-VO (Pulsinelli et al, 1979).…”

Section: Discussionmentioning

confidence: 99%

Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats

2008

View full text Add to dashboard Cite

The blood flow in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) and Wistar Kyoto (WKY) rats during occlusion of the carotid arteries was examined because it has been previously found that 2-vessel occlusion (2-VO) induces delayed neuronal death (DND) in the pyramidal cells of the CA1 hippocampal area in SHRSPs but not in WKY rats. DND was also examined in 4-week-old SHRSPs, which are as yet normotensive, in order to reveal the involvement of the development and maintenance of severe hypertension in DND in SHRSPs.Before, during and after occlusion, the blood flow in the hippocampus was continuously monitored by laser Doppler flowmetry, wherein the probe was connected to a plastic fiber that was implanted in the CA1 subfield of animals. The change in blood flow was determined by comparing its rate during occlusion to the preoperative value. DND was confirmed by histological examination at 7 days after the operation.The rate of blood flow during 2-VO was similar between the SHRSPs (42.6% ± 5.3%) and WKY rats (49.0% ± 14.3%). WKY rats that underwent 4-vessel occlusion (4-VO), which induces DND in WKY rats, exhibited a severely decreased blood flow of 13.7% of the preoperative value. DND was also observed in 4-week-old SHRSPs that underwent 2-VO, and the incidence was identical to that in 12-week-old SHRSPs.The present results suggest that the DND that occurs in SHRSPs due to 2-VO is not a result of the more severe reduction in blood supply during the occlusion than that in WKY rats, and secondary damage due to severe hypertension but is caused by some genetic factors due to which the pyramidal neurons of SHRSPs are more vulnerable to ischemic insult than those of WKY rats are.Classification: Section 8. Disease-Related Neuroscience

show abstract

Section: Discussionmentioning

confidence: 99%

Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats

2008

View full text Add to dashboard Cite

show abstract

“…The dose of galantamine was titrated upward in 4-mg increments over a 6-week period (4,8,12,16,20, and 24 mg daily during weeks 1, 2, 3, 4, 5, and 6, respectively). The patients continued with their maintenance dose of galantamine (24 mg/day) for an additional 4.5 months.…”

Section: Methodsmentioning

confidence: 99%

“…As with AD, it appears that the underlying cause of cognitive decline in VaD (and, therefore, AD + CVD) is cholinergic dysfunction. Decreased acetylcholine levels and nicotinic receptor dysfunction have both been implicated in the development and progression of cognitive decline in animal and human studies of VaD [4][5][6][7][8][9][10][11]. Thus, it is reasonable to expect that drugs used to manage cognitive decline in patients with AD also may be useful in patients with AD + CVD.…”

Section: Introductionmentioning

confidence: 99%

Management of Patients with Alzheimer’s Disease plus Cerebrovascular Disease: 12-Month Treatment with Galantamine

Bullock¹,

Erkinjuntti²,

Lilienfeld³

et al. 2003

Dement Geriatr Cogn Disord

View full text Add to dashboard Cite

We evaluated the long-term cognitive effects and safety of galantamine 24 mg/day in patients with Alzheimer’s disease plus cerebrovascular disease (AD + CVD or mixed dementia). Subgroup analysis was performed of patients with AD + CVD who participated in a 6-month, multicenter, randomized, double-blind, parallel-group study and a 6-month, open-label, active-treatment extension. Method: Two hundred and eighty-five patients with AD + CVD were randomized to receive either placebo (n = 97) or galantamine 24 mg/day (n = 188) for 6 months. Two hundred and thirty-eight (84%) patients continued with the open-label phase of the study (86 from the placebo group, 152 from the galantamine group) and were treated with galantamine 24 mg/day. The primary efficacy measure was cognitive performance as assessed using the eleven-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog/11). Standard safety evaluations and adverse-event monitoring were performed throughout the 12-month study period. Patients with AD + CVD treated with galantamine experienced statistically and clinically significant improvement in cognition at month 6 (mean change in ADAS-cog/11 score –1.1; p ≤ 0.05 vs. baseline) and maintained their cognitive function for the entire 12-month study (mean change in ADAS-cog/11 score +0.1). In contrast, the cognitive function deteriorated among those in the placebo group (mean change in ADAS-cog/11 at month 6 +2.0; p ≤ 0.001 vs. baseline). Patients with AD + CVD who were switched from placebo to galantamine for the open-label phase of the trial did show improvement in cognitive function; however, they never attained the same cognitive level as patients who had been treated with galantamine for the entire 12 months [mean (± SE) ADAS-cog/11 scores in the placebo/galantamine group 25.7 ± 1.32 and 24.2 ± 1.57 at months 6 and 12, respectively, and in the galantamine/galantamine group 21.5 ± 0.87 and 22.2 ± 1.06 at months 6 and 12, respectively]. The results of this subgroup analysis indicate that galantamine is effective for long-term maintenance of the cognitive function in patients with AD + CVD and is safe and well tolerated in this patient population.

show abstract

“…8,9 SHRSP is also well known as an excellent model for subcortical vascular dementia accompanied by small-vessel pathology, because these rats show structural alterations of small cerebral arteries, 10 reduction in cerebral blood flow, 11 white matter lesions 12,13 and cognitive impairment. 14,15 We then examined differences in gene expression between microdissected hippocampal vessels with BBB impairment in SHRSP and those without the impairment in Wistar Kyoto (WKY) rats using a microarray assay and reported that the expression of osteopontin, a matricellular protein, was increased in BBB-damaged vessels in hypertensive SHRSP compared with that in vessels without BBB impairment in WKY rats. 16 The study also indicated that the immunoreactivity of osteopontin was present in perivascular ED1-positive macrophage/microglial cells and suggested the possibility that osteopontin might act as an inducible modulator of vascular remodeling, which likely restored BBB function in the damaged blood vessels.…”

Section: Introductionmentioning

confidence: 99%

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Ueno

Nishiyama

et al. 2009

Hypertens Res

View full text Add to dashboard Cite

We previously reported that the blood-brain barrier (BBB) function was deteriorated in vessels located in the hippocampus, but not the cerebral cortex, in 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP). Recently published data suggest that matrix metalloproteinase (MMP)-2 and MMP-9 play a critical role in the BBB disruption in stroke or cerebral ischemia. In this study, we examined gene and protein expressions of MMPs in the BBB-damaged hippocampal vessels of 3-month-old SHRSP, in the cerebral cortical vessels without BBB damage of SHRSP, and in the hippocampal and cerebral cortical ones without BBB damage of 3-month-old Wistar Kyoto (WKY) rats. The expressions of MMPs were examined by real-time quantitative reverse transcriptase-PCR (RT-PCR), western blotting and immunohistochemical techniques. The gene and protein expressions of MMP-13 were significantly increased in the hippocampal samples of SHRSP compared with samples without BBB damage, such as cerebral cortical samples of SHRSP or hippocampal samples of WKY. Immunostaining of MMP-13 was seen in the cytoplasm of ED-1-positive perivascular cells in both rats and was colocalized with those of type IV collagen or osteopontin. The type IV collagen was also localized in the basement membrane. These findings indicate that the expression of MMP-13 is increased in BBB-damaged hippocampal vessels in hypertensive SHRSP compared with vessels without BBB impairment in normotensive WKY rats and may be involved in vascular remodeling. Keywords: blood-brain barrier; MMP-13; SHRSP INTRODUCTION A causative role of blood-brain barrier (BBB) impairment is suggested in the pathogenesis of vascular dementia with leakage of serum components from small vessels leading to neuronal and glial damage. 1 To clarify the roles of BBB impairment in vascular dementia, we have examined BBB function in various conditions related to vascular dementia, such as hypertension, acute ischemia with reperfusion, chronic cerebral hypoperfusion and aging with or without memory deficits. [2][3][4] Consequently, among these animal models, the most localized BBB impairment was clearly seen in the hippocampus, but not the cerebral cortex, of 3-month-old spontaneously hypertensive rats (SHR), especially of 3-month-old stroke-prone SHR (SHRSP), 4 which were established by Okamoto and Aoki 5 and are described in detail elsewhere. 6,7 It is known that the neuronal loss occurs with a reduction of gray matter volume in the CA1 subfield and dentate gyrus of the hippocampus in SHR at the age of 6 months or order, indicating that SHR can be a good animal model of vascular

show abstract

Animal Models of Vascular Dementia With Emphasis on Stroke‐prone Spontaneously Hypertensive Rats

Cited by 56 publications

References 7 publications

Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats

Mild ischemia produces hippocampal neuronal death in stroke-prone spontaneously hypertensive rats

Management of Patients with Alzheimer’s Disease plus Cerebrovascular Disease: 12-Month Treatment with Galantamine

The expression of matrix metalloproteinase-13 is increased in vessels with blood–brain barrier impairment in a stroke-prone hypertensive model

Contact Info

Product

Resources

About