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

Mohammad Badruzzaman Khan, Sherif Hafez, Md Nasrul Hoda, Babak Baban, Jesse Wagner, Mohamed E. Awad, Hasith Sangabathula, Stephen Haigh, Mohammed Elsalanty, Jennifer L. Waller, David C. Hess

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)51-63
Number of pages13
JournalTranslational Stroke Research
Volume9
Issue number1
DOIs
StatePublished - Feb 1 2018

Keywords

  • Angiogenesis, collateral remodeling, white matter degeneration
  • Cerebral blood flow (CBF)
  • Chronic remote ischemic conditioning (C-RIC)
  • Vascular contributions to cognitive impairment and dementia (VCID)

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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