The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia

Azuma, Tsukasa; Nagai, Yoshitaka; Saitô, Toshio; Funauchi, Masahiro; Matsubara, Tsuyoshi; Sakoda, Saburo

doi:10.1016/s0022-510x(98)00295-0

Cited by 23 publications

(12 citation statements)

References 25 publications

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“…30 DHEAS improved infarct-induced decrease of daily activity and emotional disturbances and also normalized the EEG. 30 Moreover, DHEAS was shown to be safe for administration to patients. Furthermore, steroids have been administered empirically to stroke victims for many years without proof of efficacy or safety.…”

Section: Discussionmentioning

confidence: 86%

Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model

Lapchak

Chapman

Nunez

et al. 2000

Stroke

109

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Background and Purpose-Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may function as neurotrophic or neuroprotective factors to protect central nervous system (CNS) neurons against a variety of insults, including excitotoxicity. The present study evaluated the pharmacological effects of DHEAS in a reversible spinal cord ischemia model. Methods-DHEAS was administered (50 mg/kg IV) 5 or 30 minutes after the start of occlusion to groups of rabbits exposed to ischemia induced by temporary (15 to 60 minutes) occlusion of the infrarenal aorta. The group P 50 represents the duration of ischemia (in minutes) associated with 50% probability of resultant permanent paraplegia. Results-The P 50 of the vehicle-treated control group, when behavioral analysis was assessed 18 hours after aortal occlusion, was 28.8Ϯ2.0 minutes. Neuroprotection was demonstrated if a drug significantly prolonged the P 50 compared with the vehicle-treated control group. Treatment with DHEAS at 5 minutes significantly (PϽ0.05) prolonged the P 50 of the group to 36.8Ϯ3.9 minutes. In addition, the DHEAS effect appeared durable, because a significant difference between the control and DHEAS-treated groups was still measurable at the 4-day time point. At 4 days, the P 50 of the control group was 26.1Ϯ2.2 minutes, whereas the P 50 for the DHEAS-treated group was 38.6Ϯ5.9 minutes. DHEAS was not neuroprotective if administered 30 minutes after occlusion. In addition, the GABA A antagonist bicuculline abolished the neuroprotective effect of DHEAS. Conclusions-The present study suggests that neurosteroids may have substantial therapeutic benefit for the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 86%

Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model

Lapchak

Chapman

Nunez

et al. 2000

Stroke

109

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“…Moreover, administration of DHEA for a period of 5 days (40 mg/kg), induced the formation of new neurons in the dentate gyrus and hippocampus of adult rats (26). Finally, daily administration of DHEAS (200 mg/day) for 4 weeks markedly increased CSF levels of DHEAS in humans (27).…”

Section: Discussionmentioning

confidence: 96%

PPAR-α Expression Inversely Correlates with Inflammatory Cytokines IL-1β and TNF-α in Aging Rats

Gelinas

McLaurin

2005

Neurochem Res

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Dehydroepiandrosterone (DHEAS) was given the name "fountain of youth" in reference to its beneficial properties in memory, cognition and aging. Cultured cell studies showed that DHEAS may mediate its action by counteracting aging-associated inflammation via PPAR-alpha activation. In the present study, we demonstrated an age-dependent increase in IL-1beta and TNF-alpha expression in the brain and the spleen of aging rats, while PPAR-alpha expression was decreased in the spleen of 18 month-old rats. Oral treatment with DHEAS increased PPAR-alpha mRNA in 3 month-old rats and decreased PPAR-alpha protein expression in 18 month-old rats in the spleen. In contrast, DHEAS did not alter cytokine expression in spleen and brain of the three age groups. These findings underline a differential role for DHEAS in PPAR-alpha expression that is age-dependent, and also, that beneficial effects of DHEAS on cognitive function are unlikely mediated by a decrease in cytokine expression.

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“…DHEA(S) concentrations are not clearly associated with cognition in dementia; however, it may be important to compare relative concentrations of DHEA-to-DHEAS and other metabolites of DHEA. Patients with Alzheimer’s disease and/or multi-infarct dementia have been reported to exhibit decreased [17; 34; 62; 91; 216; 223; 288; 304; 306; 344], as well as increased or unchanged [38; 40; 92; 172; 276; 291] plasma, serum and CSF DHEA(S) concentrations. In several instances, plasma and serum DHEA(S)-to-cortisol ratios distinguish demented participants from controls better than DHEA(S) or cortisol concentrations alone [12; 73; 170; 171; 192].…”

Section: Dhea(s) Concentrations and Neuropsychiatric Illnessesmentioning

confidence: 99%

“…DHEA could play a beneficial role in Alzheimer’s disease since DHEA has been found to be neuroprotective against amyloid β protein (Aβ) toxicity [53], to decrease lipid peroxidation in human brain tissue from patients with Alzheimer’s disease [24], and to decrease the BACE enzyme that initiates Aβ production [311]. In one study, open-label DHEAS administration (200 mg/day, intravenously, for 4 weeks) improved psychometric test performance in 4 of 7 patients with multi-infarct dementia [17]. In three of these cases, the improvements were judged clinically significant, and in two cases, electroencephalogram (EEG) patterns showed improvement with DHEAS treatment [17].…”

Section: Dhea(s) Treatment Effectsmentioning

confidence: 99%

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

Maninger

Wolkowitz

Reus

et al. 2009

Frontiers in Neuroendocrinology

617

575

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DHEA and DHEAS are steroids synthesized in human adrenals, but their function is unclear. In addition to adrenal synthesis, evidence also indicates that DHEA and DHEAS are synthesized in the brain, further suggesting a role of these hormones in brain function and development. Despite intensifying research into the biology of DHEA and DHEAS, many questions concerning their mechanisms of action and their potential involvement in neuropsychiatric illnesses remain unanswered. We review and distill the preclinical and clinical data on DHEA and DHEAS, focusing on (i) biological actions and putative mechanisms of action, (ii) differences in endogenous circulating concentrations in normal subjects and patients with neuropsychiatric diseases, and (iii) the therapeutic potential of DHEA in treating these conditions. Biological actions of DHEA and DHEAS include neuroprotection, neurite growth, and antagonistic effects on oxidants and glucocorticoids. Accumulating data suggest abnormal DHEA and/or DHEAS concentrations in several neuropsychiatric conditions. The evidence that DHEA and DHEAS may be fruitful targets for pharmacotherapy in some conditions is reviewed.

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The effect of dehydroepiandrosterone sulfate administration to patients with multi-infarct dementia

Cited by 23 publications

References 25 publications

Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model

Dehydroepiandrosterone Sulfate Is Neuroprotective in a Reversible Spinal Cord Ischemia Model

PPAR-α Expression Inversely Correlates with Inflammatory Cytokines IL-1β and TNF-α in Aging Rats

Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)

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