Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients

Runrun Wang; Jiewen Zhang; Junkui Shang; Fengyu Wang; Xi Yan

doi:10.7555/JBR.36.20220006

Volume 36 Issue 5

Sep. 2022

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Runrun Wang, Jiewen Zhang, Junkui Shang, Fengyu Wang, Xi Yan. Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients[J]. The Journal of Biomedical Research, 2022, 36(5): 368-374. doi: 10.7555/JBR.36.20220006

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Runrun Wang, Jiewen Zhang, Junkui Shang, Fengyu Wang, Xi Yan. Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients[J]. The Journal of Biomedical Research, 2022, 36(5): 368-374. doi: 10.7555/JBR.36.20220006

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Effects of different regional cerebral blood flow on white matter hyperintensity in CADASIL patients

doi: 10.7555/JBR.36.20220006

Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China

Funds: This work was supported by National Natural Science Foundation of China (Grants No. 81873727 and 82171196).

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Corresponding author: Xi Yan, Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, No. 7 Weiwu Road, Zhengzhou, Henan 450003, China. Tel: +86-371-65580782, E-mail: yanxi20091001@163.com
Received: 2022-01-07
Revised: 2022-07-11
Accepted: 2022-07-22

Published: 2022-08-28

Issue Date: 2022-09-28

Abstract

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an early-onset inherited small vessel disease. Decreased cerebral blood flow (CBF) may contribute to white matter hyperintensity (WMH) severity in CADASIL, but more evidence is needed to support this hypothesis. This study comprised six patients with CADASIL who harbored mutations in the coding sequence of NOTCH3 and twelve age-matched neurologically healthy controls. We collected clinical and imaging data from patients with CADASIL and divided the brain into four regions: WMH, normal-appearing white matter (NAWM), gray matter (GM), and global brain. We analyzed the relationship between CBF of each region and the WMH volume. Compared with the control group, CBF was significantly decreased in all four regions in the CADASIL group. Lower CBF in these regions was correlated with higher WMH volume in CADASIL. CBF in the NAWM, GM and global regions was positively correlated with that in WMH region. However, after correction tests, only CBF in the WMH region but not in NAWM, GM and global regions was associated with WMH volume. Our findings suggest that CBF in the WMH region is an influencing factor of the WMH severity in CADASIL.
- cerebral hypoperfusion,
- neurovascular unit,
- white matter hyperintensity,
- small vessel disease,
- CADASIL

CLC number: R743, Document code: A
The authors reported no conflict of interests.

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References(29)

References

[1]	Joutel A, Corpechot C, Ducros A, et al. Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia[J]. Nature, 1996, 383(6602): 707–710. doi: 10.1038/383707a0
[2]	Mašek J, Andersson ER. The developmental biology of genetic Notch disorders[J]. Development, 2017, 144(10): 1743–1763. doi: 10.1242/dev.148007
[3]	Villa N, Walker L, Lindsell CE, et al. Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels[J]. Mech Dev, 2001, 108(1–2): 161–164. doi: 10.1016/s0925-4773(01)00469-5
[4]	Schoemaker D, Arboleda-Velasquez JF. Notch3 signaling and aggregation as targets for the treatment of CADASIL and other NOTCH3-associated small-vessel diseases[J]. Am J Pathol, 2021, 191(11): 1856–1870. doi: 10.1016/j.ajpath.2021.03.015
[5]	Gatti JR, Zhang X, Korcari E, et al. Redistribution of mature smooth muscle markers in brain arteries in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. Transl Stroke Res, 2019, 10(2): 160–169. doi: 10.1007/s12975-018-0643-x
[6]	Joutel A, Favrole P, Labauge P, et al. Skin biopsy immunostaining with a Notch3 monoclonal antibody for CADASIL diagnosis[J]. Lancet, 2001, 358(9298): 2049–2051. doi: 10.1016/S0140-6736(01)07142-2
[7]	Joutel A, Andreux F, Gaulis S, et al. The ectodomain of the Notch3 receptor accumulates within the cerebrovasculature of CADASIL patients[J]. J Clin Invest, 2000, 105(5): 597–605. doi: 10.1172/JCI8047
[8]	Hack RJ, Gravesteijn G, Cerfontaine MN, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy family members with a pathogenic NOTCH3 variant can have a normal brain magnetic resonance imaging and skin biopsy beyond age 50 years[J]. Stroke, 2022, 53(6): 1964–1974. doi: 10.1161/STROKEAHA.121.036307
[9]	Yao M, Jouvent E, During M, et al. Extensive white matter hyperintensities may increase brain volume in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. Stroke, 2012, 43(12): 3252–3257. doi: 10.1161/STROKEAHA.112.664854
[10]	Joutel A, Monet-Leprêtre M, Gosele C, et al. Cerebrovascular dysfunction and microcirculation rarefaction precede white matter lesions in a mouse genetic model of cerebral ischemic small vessel disease[J]. J Clin Invest, 2010, 120(2): 433–445. doi: 10.1172/JCI39733
[11]	Iadecola C. Neurovascular regulation in the normal brain and in Alzheimer's disease[J]. Nat Rev Neurosci, 2004, 5(5): 347–360. doi: 10.1038/nrn1387
[12]	Schaeffer S, Iadecola C. Revisiting the neurovascular unit[J]. Nat Neurosci, 2021, 24(9): 1198–1209. doi: 10.1038/s41593-021-00904-7
[13]	Kisler K, Nelson AR, Montagne A, et al. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease[J]. Nat Rev Neurosci, 2017, 18(7): 419–434. doi: 10.1038/nrn.2017.48
[14]	Kugler EC, Greenwood J, MacDonald RB. The "neuro-glial-vascular" unit: the role of glia in neurovascular unit formation and dysfunction[J]. Front Cell Dev Biol, 2021, 9: 732820. doi: 10.3389/fcell.2021.732820
[15]	Bruening R, Dichgans M, Berchtenbreiter C, et al. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance[J]. AJNR Am J Neuroradiol, 2001, 22(7): 1268–1274. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975190/
[16]	Liem MK, Oberstein SAJL, Haan J, et al. Cerebrovascular reactivity is a main determinant of white matter hyperintensity progression in CADASIL[J]. AJNR Am J Neuroradiol, 2009, 30(6): 1244–1247. doi: 10.3174/ajnr.A1533
[17]	Sun C, Wu Y, Ling C, et al. Reduced blood flow velocity in lenticulostriate arteries of patients with CADASIL assessed by PC-MRA at 7T[J]. J Neurol Neurosurg Psychiatry, 2022, 93(4): 451–452. doi: 10.1136/jnnp-2021-326258
[18]	Uchida Y, Kan H, Sakurai K, et al. Iron leakage owing to blood-brain barrier disruption in small vessel disease CADASIL[J]. Neurology, 2020, 95(9): e1188–e1198. doi: 10.1212/WNL.0000000000010148
[19]	Ruchoux MM, Guerouaou D, Vandenhaute B, et al. Systemic vascular smooth muscle cell impairment in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy[J]. Acta Neuropathol, 1995, 89(6): 500–512. doi: 10.1007/BF00571504
[20]	Barkaway A, Attwell D, Korte N. Immune-vascular mural cell interactions: consequences for immune cell trafficking, cerebral blood flow, and the blood-brain barrier[J]. Neurophotonics, 2022, 9(3): 031914. doi: 10.1117/1.NPh.9.3.031914
[21]	Brennan-Krohn T, Salloway S, Correia S, et al. Glial vascular degeneration in CADASIL[J]. J Alzheimers Dis, 2010, 21(4): 1393–1402. doi: 10.3233/JAD-2010-100036
[22]	Hase Y, Chen A, Bates LL, et al. Severe white matter astrocytopathy in CADASIL[J]. Brain Pathol, 2018, 28(6): 832–843. doi: 10.1111/bpa.12621
[23]	Jolly AA, Nannoni S, Edwards H, et al. Prevalence and predictors of vascular cognitive impairment in patients with CADASIL[J]. Neurology, 2022, 95(5): e453–e461. doi: 10.1212/WNL.0000000000200607
[24]	Manini A, Pantoni L. CADASIL from bench to bedside: disease models and novel therapeutic approaches[J]. Mol Neurobiol, 2021, 58(6): 2558–2573. doi: 10.1007/s12035-021-02282-4
[25]	Chabriat H, Levy C, Taillia H, et al. Patterns of MRI lesions in CADASIL[J]. Neurology, 1998, 51(2): 452–457. doi: 10.1212/WNL.51.2.452
[26]	Yin X, Zhou Y, Yan S, et al. Effects of cerebral blood flow and white matter integrity on cognition in CADASIL patients[J]. Front Psychiatry, 2019, 9: 741. doi: 10.3389/fpsyt.2018.00741
[27]	Baron-Menguy C, Domenga-Denier V, Ghezali L, et al. Increased Notch3 activity mediates pathological changes in structure of cerebral arteries[J]. Hypertension, 2017, 69(1): 60–70. doi: 10.1161/HYPERTENSIONAHA.116.08015
[28]	Mellies JK, Bäumer T, Müller JA, et al. SPECT study of a German CADASIL family: a phenotype with migraine and progressive dementia only[J]. Neurology, 1998, 50(6): 1715–1721. doi: 10.1212/WNL.50.6.1715
[29]	Moreton FC, Cullen B, Delles C, et al. Vasoreactivity in CADASIL: comparison to structural MRI and neuropsychology[J]. J Cereb Blood Flow Metab, 2018, 38(6): 1085–1095. doi: 10.1177/0271678X17710375