Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model

• Published in: Translational stroke research Vol. 9; no. 1; pp. 51 - 63
• Main Authors: Khan, Mohammad Badruzzaman, Hafez, Sherif, Hoda, Md. Nasrul, Baban, Babak, Wagner, Jesse, Awad, Mohamed E., Sangabathula, Hasith, Haigh, Stephen, Elsalanty, Mohammed, Waller, Jennifer L., Hess, David C.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2018; Springer Nature B.V
• Subjects: Angiogenesis; Animal cognition; Biomedical and Life Sciences; Biomedicine; Brain research; Cardiology; Carotid arteries; Cognitive ability; Dementia; Exercise; Ischemia; Laboratory animals; Neurology; Neurosciences; Neurosurgery; Original; Original Article; Plasma; Proteins; Surgery; Vascular Surgery; Veins & arteries; United States > US; Chronic remote ischemic conditioning (C-RIC); Angiogenesis, collateral remodeling, white matter degeneration; Vascular contributions to cognitive impairment and dementia (VCID); Cerebral blood flow (CBF)
• ISSN: 1868-4483; 1868-601X
• DOI: 10.1007/s12975-017-0555-1

Vascular contributions to cognitive impairment and dementia (VCID) make up 50% of the cases of dementia. The purpose of this study was to determine the effect of chronic remote ischemic conditioning (C-RIC) on improving long-term (6 months) outcomes and cerebral blood flow (CBF) and collateral formation in a mouse model of VCID. Adult C57BL/6J male mice (10 weeks) were randomly assigned to four different groups: (1) sham-bilateral carotid artery stenosis (BCAS), (2) BCAS + sham RIC, (3) BCAS+C-RIC for 1 month (1MO), and (4) BCAS+C-RIC-4 months (4MO). CBF, cognitive impairment, and functional outcomes were performed up for 6 months after BCAS surgery. The expression of CD31, α-SMA, and myelin basic protein (MBP) was assessed by immunohistochemistry (IHC). Additional set of mice were randomized to sham, BCAS, and BCAS+C-RIC. The cerebrovascular angioarchitecture was studied with micro-CT. RIC therapy for either 1 or 4 months significantly improved CBF, new collateral formation, functional and cognitive outcomes, and prevented white matter damage. There was no difference between C-RIC for 1 or 4 months; IHC studies at 6 months showed an increase in brain CD31 and α-SMA expression indicating increased angiogenesis and MBP indicating preservation of white matter in animals receiving RIC. One month of daily RIC is as effective as 4 months of daily RIC in improving CBF, angiogenesis, and long-term functional outcomes (6 months) in a VCID model. This suggests that 1 month of RIC is sufficient to reduce cognitive impairment and induce beneficial cerebrovascular remodeling.