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Updated: Jan 31, 2026
Using Retinal Imaging to Study Dementia
Published on: November 6, 2017
Sildenafil treatment of vascular dementia in aged rats
Poornima Venkat1, Michael Chopp2, Alex Zacharek1
1Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA.
Background:
and purpose: In this study, we employed a multiple microinfarction (MMI) based vascular dementia (VaD) model in aged rats and tested the therapeutic effects of Sildenafil, a phosphodiesterase type 5 inhibitor, on cognitive decline, white matter damage, autophagy and inflammatory response associated with VaD.
Methods:
Male, aged (16-18 months) Wistar rats were subjected to MMI (800 ± 100, 70-100 microm cholesterol crystals injected into the internal carotid artery) and treated with or without Sildenafil (2 mg/kg, i.p) starting at 24 h after MMI daily for 28 days. Four experimental groups were employed: Sham control, Sham + Sildenafil, MMI, and MMI + Sildenafil. A battery of cognitive tests were performed and rats were sacrificed at 28 days after MMI for immunohistochemical evaluation and PCR assay.
Results:
Sildenafil treatment in aged MMI rats significantly improves short term memory evaluated by the novel object recognition test and improves spatial learning and memory in the Morris water maze test compared to aged control MMI rats. Sildenafil treatment of aged MMI rats significantly increases axon and myelin density in the corpus callosum and white matter bundles in the striatum, increases oligodendrocyte and oligodendrocyte progenitor cell number in the corpus callosum, cortex and striatum, and increases synaptic protein expression in the cortex and striatum compared to aged control MMI rats. In addition, Sildenafil treatment of MMI in aged rats significantly decreases Beclin1 expression and inflammatory factors Monocyte chemoattractant protein-1 and Interleukin-1β expression in brain. Sildenafil treatment in aged rats does not improve cognitive outcome compared to aged sham control rats.
Conclusions:
Sildenafil treatment of MMI in aged rats significantly improves cognition and memory at 1 month after MMI. Sildenafil treatment increases axon and myelin density, increases Synaptophysin expression, decreases autophagic activity and exerts anti-inflammatory effects which in concert may contribute to cognitive improvement in aged rats subjected to MMI.
Insights
Sildenafil improved cognitive function and memory in aged rats with vascular dementia. The treatment enhanced white matter integrity, reduced inflammation, and decreased autophagy, suggesting therapeutic potential for vascular dementia.
Area of Science:
- Neuroscience
- Pharmacology
- Pathology
Background:
- Vascular dementia (VaD) is a significant cause of cognitive decline.
- Multiple microinfarction (MMI) is a common model for studying VaD.
- Aged rats are used to mimic age-related cognitive impairments seen in VaD.
Purpose of the Study:
- To investigate the therapeutic effects of Sildenafil on cognitive decline in an aged rat model of VaD.
- To assess Sildenafil's impact on white matter damage, autophagy, and inflammation in VaD.
Main Methods:
- An MMI model was induced in aged Wistar rats using cholesterol crystals.
- Rats were treated with Sildenafil (2 mg/kg) or a placebo daily for 28 days.
- Cognitive function was evaluated using behavioral tests; brain tissues were analyzed for histological and molecular changes.
Main Results:
- Sildenafil significantly improved short-term memory and spatial learning/memory in MMI rats.
- Treatment increased axon and myelin density, oligodendrocyte numbers, and synaptic protein expression.
- Sildenafil reduced Beclin1, Monocyte chemoattractant protein-1, and Interleukin-1β expression, indicating decreased autophagy and inflammation.
Conclusions:
- Sildenafil treatment ameliorates cognitive and memory deficits in aged rats with MMI-induced VaD.
- Improvements are associated with enhanced white matter integrity, reduced autophagy, and anti-inflammatory effects.
- Sildenafil shows promise as a therapeutic agent for vascular dementia.
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