TY  - JOUR
N2  - BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.
Y1  - 2024/07//
JF  - Stroke
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ID  - discovery10194138
VL  - 55
PB  - Ovid Technologies (Wolters Kluwer Health)
UR  - https://doi.org/10.1161/STROKEAHA.124.047154
TI  - Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease
AV  - public
SN  - 0039-2499
EP  - 1922
IS  - 7
KW  - calcium channel blockers
KW  -  cerebrovascular circulation
KW  -  neurovascular coupling
KW  -  open field test
KW  -  rats
KW  -  inbred SHR
KW  -  spectroscopy
KW  -  near-infrared
A1  - Yang, Zhiyuan
A1  - Lange, Frédéric
A1  - Xia, Yiqing
A1  - Chertavian, Casey
A1  - Cabolis, Katerina
A1  - Sajic, Marija
A1  - Werring, David J
A1  - Tachtsidis, Ilias
A1  - Smith, Kenneth J
SP  - 1914
ER  -