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Clemastine ameliorates cognitive deficits in an experimental rat model of chronic cerebral hypoperfusion
Xuemei Zong1, Zhihai Huang1, Fanfei Kong1
1Department of Neurology, Institute for Cerebrovascular and Neuroregeneration Research (ICNR), Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Insights
Enhanced myelination may prevent cognitive decline in chronic cerebral hypoperfusion (CCH). Clemastine, a pro-myelinating drug, preserved cognitive function and synaptic integrity in rats with CCH.
Area of Science:
- Neuroscience
- Neurology
- Pharmacology
Background:
- Chronic cerebral hypoperfusion (CCH) is linked to cognitive impairment and dementia.
- Current understanding of CCH pathophysiology is limited, hindering effective treatments.
- New therapeutic targets for CCH-associated cognitive deficits are urgently needed.
Purpose of the Study:
- To investigate if enhanced myelination can prevent cognitive impairment in CCH.
- To explore clemastine as a potential therapeutic agent for CCH.
Main Methods:
- Experimental CCH was induced in rats using bilateral common carotid artery occlusion (BCCAO).
- Clemastine was administered to promote myelin repair.
- Cognitive function was assessed using behavioral tests.
- Brain tissue was analyzed for myelin integrity, synaptic structure, and neurovascular function.
Main Results:
- BCCAO induced significant cognitive deficits, myelin loss, and synaptic dysfunction in rats.
- Myelin loss and synaptic disruption occurred without significant neuronal loss or oligodendrocyte apoptosis.
- Clemastine treatment preserved dendritic spine density and prevented cognitive deficits and neurovascular dysfunction.
Conclusions:
- Enhanced myelination through clemastine shows promise in preventing CCH-associated cognitive impairment.
- Myelin integrity and synaptic function are critical targets for therapeutic intervention in CCH.
- Clemastine represents a potential therapeutic strategy for cognitive deficits resulting from CCH.
Abstract:
Chronic cerebral hypoperfusion (CCH) profoundly affects patient well-being and has been proposed as a risk factor for cognitive impairment and dementia. However, due to the limited understanding of the pathophysiology of CCH, there are currently no effective preventive or therapeutic approaches for CCH-associated cognitive impairment. Therefore, identifying new targets for CCH is essential to bridge this knowledge gap. In this study, we sought to determine whether enhanced myelination could prevent cognitive impairment associated with CCH. Experimental CCH was induced via bilateral common carotid artery occlusion (BCCAO) in rats, and clemastine, a well-established pro-myelinating agent, was administered to boost myelin renewal. A series of behavioral tests was performed to assess learning and memory. We found that animals exhibited profound cognitive deficits 3 months after BCCAO, accompanied by significant myelin loss, structural disruption at the nodes of Ranvier, and synaptic dysfunction in various brain regions, without notable neuronal loss and oligodendrocyte apoptosis. Importantly, pharmacological enhancement of myelination preserved dendritic spine density and prevented synaptic loss, cognitive deficits, and neurovascular dysfunction following BCCAO. These findings suggest that clemastine may represent a promising therapeutic option for CCH-associated cognitive impairment.
