TY - JOUR
T1 - Chronic Remote Ischemic Conditioning Is Cerebroprotective and Induces Vascular Remodeling in a VCID Model
AU - Khan, Mohammad Badruzzaman
AU - Hafez, Sherif
AU - Hoda, MD Nasrul
AU - Baban, Babak
AU - Wagner, Jesse
AU - Awad, Mohamed E.
AU - Sangabathula, Hasith
AU - Haigh, Stephen
AU - Elsalanty, Mohammed Elsayed
AU - Waller, Jennifer L.
AU - Hess, David C.
N1 - Funding Information:
This work was supported by the NIH/NINDS R21NS090609-01A1. We are special thankful to Mr. Richard Goodman, Hatteras Instruments, Cary, NC, in accepting a proposed design and making a multichannel non-invasive programmable remote ischemic conditioner and for a generous gift to our laboratory. The authors declare that they have no conflict of interest.
Funding Information:
Funding This work was supported by the NIH/NINDS R21NS090609-01A1. We are special thankful to Mr. Richard Goodman, Hatteras Instruments, Cary, NC, in accepting a proposed design and making a multichannel non-invasive programmable remote ischemic conditioner and for a generous gift to our laboratory.
Publisher Copyright:
© 2017, The Author(s).
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
KW - Angiogenesis, collateral remodeling, white matter degeneration
KW - Cerebral blood flow (CBF)
KW - Chronic remote ischemic conditioning (C-RIC)
KW - Vascular contributions to cognitive impairment and dementia (VCID)
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U2 - 10.1007/s12975-017-0555-1
DO - 10.1007/s12975-017-0555-1
M3 - Article
C2 - 28755277
AN - SCOPUS:85026467165
SN - 1868-4483
VL - 9
SP - 51
EP - 63
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 1
ER -