Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats

Torre, Jack C. de la; Fortin, T.; Park, G. A. S.; Butler, Keith W.; Kozłowski, Piotr; Pappas, Bruce A.; Socarraz, H. de; Saunders, John K.; Richard, Marie-Claude

doi:10.1016/0006-8993(92)90132-s

Cited by 156 publications

(85 citation statements)

References 38 publications

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“…In contrast, the more modest increases in plasma homocysteine induced in the present study better reflect the epidemiological associations of mild hyperhomocysteinemia and cognitive impairment. Based on structural evidence from the present study, we argue that the reduced abundance of brain Glut-1 and other vascular proteins found in other in vivo models (9) is likely to reflect capillary loss, which could then have a secondary impact on brain energy metabolism and neurovascular coupling (14,30,31).…”

Section: Hippocampal Capillary Length (Micron)mentioning

confidence: 58%

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Troen

Shea‐Budgell²,

Shukitt‐Hale³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

166

133

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In older adults, mildly elevated plasma total homocysteine (hyperhomocysteinemia) is associated with increased risk of cognitive impairment, cerebrovascular disease, and Alzheimer's disease, but it is uncertain whether this is due to underlying metabolic, neurotoxic, or vascular processes. We report here that feeding male C57BL6/J mice a B-vitamin-deficient diet for 10 weeks induced hyperhomocysteinemia, significantly impaired spatial learning and memory, and caused a significant rarefaction of hippocampal microvasculature without concomitant gliosis and neurodegeneration. Total hippocampal capillary length was inversely correlated with Morris water maze escape latencies (r ‫؍‬ ؊0.757, P < 0.001), and with plasma total homocysteine (r ‫؍‬ ؊0.631, P ‫؍‬ 0.007). Feeding mice a methionine-rich diet produced similar but less pronounced effects. Our findings suggest that cerebral microvascular rarefaction can cause cognitive dysfunction in the absence of or preceding neurodegeneration. Similar microvascular changes may mediate the association of hyperhomocysteinemia with human age-related cognitive decline. cerebrovascular ͉ homocysteine ͉ mouse ͉ nutrition

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Section: Hippocampal Capillary Length (Micron)mentioning

confidence: 58%

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Troen

Shea‐Budgell²,

Shukitt‐Hale³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

166

133

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“…Although patients had no strategic infarcts in the hippocampus, it is conceivable that a cerebral volume deficit, including the medial temporal lobe, may be caused mainly or solely by cerebral substance loss induced by multiple subcortical infarcts. In an experimental study with aged rats, chronic vascular insufficiency without infarctions caused mimicked AD-type changes in the hippocampal regions, including CA1 neuron (the Sommer sector) damage and gliosis (46). Since neurons of the hippocampal formation, especially neurons of CA1 and CA3 to CA4 (the end folium), are particularly sensitive to ischemia and anoxia, acute hypoxic episodes are likely to result in nerve cell damage and subsequent gliosis.…”

Section: Discussionmentioning

confidence: 99%

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease

Hanyu

Asano

Sakurai

et al. 2001

Journal of the Neurological Sciences

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BACKGROUND AND PURPOSE:Although atrophy of structures in the medial temporal lobe has been considered an indication of Alzheimer's disease (AD), atrophic changes on MR images have also been associated with other dementing diseases and are not specific to AD. This study was undertaken to determine whether characteristic alterations in the hippocampus of patients with AD are detectable with magnetization transfer (MT) imaging.METHODS: Coronal MT imaging was performed in 35 patients with probable AD, in 14 patients with vascular dementia, in 13 patients with other types of dementia, and in 23 control subjects to measure MT ratios of the hippocampus. Medial temporal lobe atrophy was graded subjectively on a five-point scale.RESULTS: Scores of medial temporal lobe atrophy in all dementia groups were significantly higher than those in control subjects, but no differences were found among the dementia groups. MT ratios in the hippocampus were significantly lower in patients with AD than in those with non-AD dementia and in the control subjects; however, no differences were found between the non-AD dementia patients and the control subjects. MT ratio measurements were better than visual analysis of atrophy for differentiating AD patients from those with non-AD dementia (an overall discrimination rate of 77% versus 65%). MT ratios significantly correlated with scores on the Mini-Mental State Examination and with medial temporal lobe atrophy in AD patients but not in patients with non-AD dementia.CONCLUSION: MT measurements may be more specific than visual analysis in detecting structural damage of the hippocampus in AD patients and might be useful in discriminating AD from vascular dementia and other types of dementia.

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“…Atropine sulfate (0.1 mg IM) was administered to prevent respiratory distress. A ventral midline incision was made, and both common carotid arteries were gently separated from the carotid sheath and vagus nerve (de la Torre et al, 1992). Each common carotid artery was doubly ligated with 5-0 silk suture just below the internalexternal carotid bifurcation (2-VO).…”

Section: Surgerymentioning

confidence: 99%

“…After surgery, rats were placed on a heating pad to maintain body temperature until full recovery. We have reported that the surgical procedure and recovery period do not modify serum electrolytes, pH, lactate, ATP, creatine phosphate or N-acetyl aspartate levels in brain (Abdollahian et al, 1998;de la Torre et al, 1991de la Torre et al, , 1992de la Torre and Fortin, 1994). …”

Section: Surgerymentioning

confidence: 99%

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Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

Torre

Aliev

2005

J Cereb Blood Flow Metab

109

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An aging rat model of chronic brain hypoperfusion (CBH) that mimics human mild cognitive impairment (MCI) was used to examine the role of nitric oxide synthase (NOS) isoforms on spatial memory function. Rats with CBH underwent bilateral common carotid artery occlusion (2-vessel occlusion (2-VO)) for either 26 or 8 weeks and were compared with nonoccluded sham controls (S-VO). The neuronal and endothelial (nNOS/eNOS) constitutive inhibitor nitro-L-arginine methyl ester (L-NAME) 20 mg/kg was administered after 26 weeks for 3 days to 2-VO and S-VO groups and spatial memory was assessed with a modified Morris watermaze test. Only 2-VO rats worsened their spatial memory ability after L-NAME. Electron microscopic immunocytochemical examination using an antibody against eNOS showed 2-VO rats had significant loss or absence of eNOS-containing positive gold particles in hippocampal endothelium and these changes were associated with endothelial cell compression, mitochondrial damage and heavy amyloid deposition in hippocampal capillaries and perivascular region. In the 8-week study, three groups of 2-VO rats were administered an acute dose of 7-NI, aminoguanidine or L-NIO, the relatively selective inhibitors of nNOS, inducible NOS and eNOS. Only rats administered the eNOS inhibitor L-NIO worsened markedly their watermaze performance (P ¼ 0.009) when compared with S-VO nonoccluded controls. We conclude from these findings that vascular nitric oxide derived from eNOS may play a critical role in spatial memory function during CBH possibly by keeping cerebral perfusion optimal through its regulation of microvessel tone and cerebral blood flow and that disruption of this mechanism can result in spatial memory impairment. These findings may identify therapeutic targets for preventing MCI and treating Alzheimer's disease.

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Chronic cerebrovascular insufficiency induces dementia-like deficits in aged rats

Cited by 156 publications

References 38 publications

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

Magnetization transfer measurements of the hippocampus in the early diagnosis of Alzheimer's disease

Inhibition of Vascular Nitric Oxide after Rat Chronic Brain Hypoperfusion: Spatial Memory and Immunocytochemical Changes

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