Impaired Collateral Flow Compensation During Chronic Cerebral Hypoperfusion in the Type 2 Diabetic Mice.
The presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.



We examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in db/+ and db/db mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.



After unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared with db/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with db/+ mice.



Type 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Yasuo
Y
Nishijima
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Yosuke
Y
Akamatsu
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Shih Yen
SY
Yang
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Chih Cheng
CC
Lee
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Utku
U
Baran
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Shaozhen
S
Song
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Ruikang K
RK
Wang
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.).
Teiji
T
Tominaga
Department of Neurological Surgery, University of California at San Francisco (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); San Francisco Veterans Affairs Medical Center, CA (Y.N., Y.A., S.Y.Y., C.C.L., J.L.); Department of Neurosurgery, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan (Y.N., Y.A., T.T.); and Departments of Bioengineering & Ophthalmology, University of Washington, Seattle (U.B., S.S., R.K.W.). jialing.liu@ucsf.edu.
Jialing
J
Liu
D000818:Animals; D001160:Arterioles / Q000000981:diagnostic imaging*; D002533:Cerebral Angiography; D002539:Cerebral Arterial Diseases / Q000000981:diagnostic imaging* / Q000209:etiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002941:Circle of Willis / Q000000981:diagnostic imaging*; D003097:Collateral Circulation / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004195:Disease Models, Animal; D008297:Male; D008578:Meninges / Q000098:blood supply*; D051379:Mice; D061848:Optical Imaging; D012307:Risk Factors
CCAO; anastomosis; arteriogenesis; carotid occlusive disease; doppler OCT; vascular remodeling