دورية أكاديمية
أعرض في EDS

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

التفاصيل البيبلوغرافية
العنوان: Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.
المؤلفون: Yang Z; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom., Lange F; Department of Medical Physics and Biomedical Engineering (F.L., I.T.), University College London, United Kingdom., Xia Y; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom., Chertavian C; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom., Cabolis K; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom., Sajic M; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom., Werring DJ; Stroke Research Centre, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology (D.J.W.), University College London, United Kingdom., Tachtsidis I; Department of Medical Physics and Biomedical Engineering (F.L., I.T.), University College London, United Kingdom., Smith KJ; Department of Neuroinflammation, UCL Queen Square Institute of Neurology (Z.Y., Y.X., C.C., K.C., M.S., K.J.S.), University College London, United Kingdom.
المصدر: Stroke [Stroke] 2024 Jul; Vol. 55 (7), pp. 1914-1922. Date of Electronic Publication: 2024 Jun 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0235266 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4628 (Electronic) Linking ISSN: 00392499 NLM ISO Abbreviation: Stroke Subsets: MEDLINE
أسماء مطبوعة: Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins
Original Publication: Dallas : American Heart Association
مواضيع طبية MeSH: Nimodipine*/pharmacology , Nimodipine*/therapeutic use , Cerebral Small Vessel Diseases*/drug therapy , Rats, Inbred SHR* , Disease Models, Animal* , Cognition*/drug effects , Calcium Channel Blockers*/pharmacology , Calcium Channel Blockers*/therapeutic use, Animals ; Male ; Rats ; Cerebrovascular Circulation/drug effects ; Cognition Disorders/etiology ; Cognition Disorders/drug therapy ; Cognition Disorders/prevention & control
مستخلص: 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.
Competing Interests: Disclosures Dr Werring has received speaking honoraria from Bayer; speaking and chairing honoraria from Alexion Pharmaceuticals Inc and Novo Nordisk; and consultancy fees from Alnylam Pharmaceuticals, Bayer, and Novo Nordisk. Dr Tachtsidis is the CEO and founder of Metabolight Ltd.
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فهرسة مساهمة: Keywords: calcium channel blockers; cerebrovascular circulation; neurovascular coupling; open field test; rats, inbred SHR; spectroscopy, near-infrared
المشرفين على المادة: 57WA9QZ5WH (Nimodipine)
0 (Calcium Channel Blockers)
تواريخ الأحداث: Date Created: 20240611 Date Completed: 20240624 Latest Revision: 20240718
رمز التحديث: 20240718
مُعرف محوري في PubMed: PMC11251505
DOI: 10.1161/STROKEAHA.124.047154
PMID: 38860370
قاعدة البيانات: MEDLINE
الوصف
تدمد:1524-4628
DOI:10.1161/STROKEAHA.124.047154