Abstract WP480: Beneficial Effect of Chronic-Remote Ischemic Conditioning (C-RIC) is Dependent Upon Circulating Blood Cell NOS3 in a Vascular Cognitive Impairment and Dementia (VCID) Model

• Published in: Stroke (1970) 2020-02, Vol.51 (Suppl_1)
• Main Authors: Khan, Mohammad B, Siddiqui, Shahneela, Rehman, Amna, Blauenfeldt, Rolf A, Alam, Haroon, Shaikh, Muhammad F, Sharma, Abhinav, Vaibhav, Kumar, Braun, Molly, Achyut, Bhagelu R, Rashid, Mohammad H, Khodadadi, Hesamoldin, Baban, Babak, Dhandapani, Krishnan M, Hess, David C
• Format: Article
• Language: English
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/str.51.suppl_1.WP480

Abstract only Background and Purpose: Chronic remote ischemic conditioning (C-RIC) is effective at improving cerebral blood flow (CBF) inducing vascular remodeling, and improving cognition in a bilateral carotid artery stenosis (BCAS) mouse model, a model for Vascular Cognitive Impairment and Dementia (VCID). This effect is lost in NOS3-KO mice. We wanted to determine if the beneficial effect of C-RIC can be restored by bone marrow cell-derived NOS3. Methods: We prepared BM chimera from adult WT (B6.SJL-Ptprc a ; CD45.1) to adult NOS3-KO (B6.129; CD45.2) & vice versa in male mice (5-6 months) following confirmation for BM engrafting with flow cytometry at 2 weeks. Microcoil (0.18 mm) induced BCAS model was used to induce chronic hypoperfusion. Mice were randomly assigned to 3-groups: (1) Sham (2) BCAS and (3) BCAS+RIC. RIC was started 7d post-surgery daily for 3-4 weeks. Behavioral test and CBF was performed before termination. Functional outcomes were assessed using novel object recognition (NOR) test for non-spatial working memory, and hanging wire and beam walk test for motor/muscular impairment. We measured whole blood P-NOS3, P-AMPK and VEGFR2/CD31 by flow cytometry. Results: C-RIC-therapy for 3-4 weeks improves CBF in engrafted BM of WT into NOS3-KO in the BCAS+RIC groups at both 2 weeks and 4 weeks compared to BCAS (Sham RIC groups).No effect of C-RIC was shown in engrafted BM of NOS3 into WT. There was significant change between the BCAS and BCAS+RIC groups in the functional outcomes and histopathological evidences also reflects major changing in the groups in the BM of WT into NOS3-KO mice. Whole blood P-NOS3, P-AMPK and VEGFR2/CD31 was increased by C-RIC. However, no effect was shown in the NOS3-KO into WT chimera. Conclusions: The Beneficial effect of C-RIC is dependent upon bone marrow derived NOS3.Further studies are needed to determine if the red blood cell is the key cell carrying NOS3