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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2014

Open Access 01-12-2014 | Research

Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease

Authors: Daniel Kaiser, Gesa Weise, Karoline Möller, Johanna Scheibe, Claudia Pösel, Sebastian Baasch, Matthias Gawlitza, Donald Lobsien, Kai Diederich, Jens Minnerup, Alexander Kranz, Johannes Boltze, Daniel-Christoph Wagner

Published in: Acta Neuropathologica Communications | Issue 1/2014

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Abstract

Introduction

Cerebral small vessel disease (cSVD) is one of the most prevalent neurological disorders. The progressive remodeling of brain microvessels due to arterial hypertension or other vascular risk factors causes subtle, but constant cognitive decline through to manifest dementia and substantially increases the risk for stroke. Preliminary evidence suggests the contribution of the immune system to disease initiation and progression, but a more detailed understanding is impaired by the unavailability of appropriate animal models. Here, we introduce the spontaneously hypertensive rat (SHR) as a model for early onset cSVD and unveiled substantial immune changes in conjunction with brain abnormalities that resemble clinical findings.

Results

In contrast to age-matched normotensive Wistar Kyoto (WKY) rats, male SHR exhibited non-spatial memory deficits. Magnetic resonance imaging showed brain atrophy and a reduction of white matter volumes in SHR. Histological analyses confirmed white matter demyelination and unveiled a circumscribed blood brain barrier dysfunction in conjunction with micro- and macrogliosis in deep cortical regions. Flow cytometry and histological analyses further revealed substantial disparities in cerebral CD45high leukocyte counts and distribution patterns between SHR and WKY. SHR showed lower counts of T cells in the choroid plexus and meningeal spaces as well as decreased interleukin-10 levels in the cerebrospinal fluid. On the other hand, both T and NK cells were significantly augmented in the SHR brain microvasculature.

Conclusions

Our results indicate that SHR share behavioral and neuropathological characteristics with human cSVD patients and further undergird the relevance of immune responses for the initiation and progression of cSVD.
Appendix
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Literature
1.
Sudlow CL, Warlow CP: Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration. Stroke 1997, 28(3):491–499. 10.1161/01.STR.28.3.491CrossRefPubMed
2.
Vermeer SE, Longstreth WT Jr, Koudstaal PJ: Silent brain infarcts: a systematic review. Lancet Neurol 2007, 6(7):611–619. 10.1016/S1474-4422(07)70170-9CrossRefPubMed
3.
Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S: Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011, 42(9):2672–2713. 10.1161/STR.0b013e3182299496CrossRefPubMedPubMedCentral
4.
Wardlaw JM, Smith C, Dichgans M: Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol 2013, 12(5):483–497. 10.1016/S1474-4422(13)70060-7CrossRefPubMed
5.
Hainsworth AH, Markus HS: Do in vivo experimental models reflect human cerebral small vessel disease? A systematic review. J Cereb Blood Flow Metab 2008, 28(12):1877–1891. 10.1038/jcbfm.2008.91CrossRefPubMed
6.
Jiwa NS, Garrard P, Hainsworth AH: Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem 2010, 115(4):814–828. 10.1111/j.1471-4159.2010.06958.xCrossRefPubMed
7.
Schreiber S, Bueche CZ, Garz C, Kropf S, Kuester D, Amann K, Heinze HJ, Goertler M, Reymann KG, Braun H: Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats. PLoS One 2011, 6(10):e26287. 10.1371/journal.pone.0026287CrossRefPubMedPubMedCentral
8.
Schreiber S, Bueche CZ, Garz C, Kropf S, Angenstein F, Goldschmidt J, Neumann J, Heinze HJ, Goertler M, Reymann KG, Braun H: The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase? J Cereb Blood Flow Metab 2012, 32(2):278–290. 10.1038/jcbfm.2011.122CrossRefPubMed
9.
Bailey EL, Wardlaw JM, Graham D, Dominiczak AF, Sudlow CL, Smith C: Cerebral small vessel endothelial structural changes predate hypertension in stroke-prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5- to 21-week-old rats. Neuropathol Appl Neurobiol 2011, 37(7):711–726. 10.1111/j.1365-2990.2011.01170.xCrossRefPubMed
10.
Yoshino H, Sakurai T, Oizumi XS, Akisaki T, Wang X, Yokono K, Kondoh T, Kohmura E, Umentani K: Dilation of perforating arteries in rat brain in response to systemic hypotension is more sensitive and pronounced than that of pial arterioles: simultaneous visualization of perforating and cortical vessels by in-vivo microangiography. Microvasc Res 2009, 77(2):230–233. 10.1016/j.mvr.2008.09.011CrossRefPubMed
11.
Maillard P, Seshadri S, Beiser A, Himali JJ, Au R, Fletcher E, Carmichael O, Wolf PA, Decarli C: Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol 2012, 11(12):1039–1047. 10.1016/S1474-4422(12)70241-7CrossRefPubMedPubMedCentral
12.
de Leeuw FE, de Kleine M, Frijns CJ, Fijnheer R, van Gijn J, Kappelle LJ: Endothelial cell activation is associated with cerebral white matter lesions in patients with cerebrovascular disease. Ann N Y Acad Sci 2002, 977: 306–314. 10.1111/j.1749-6632.2002.tb04831.xCrossRefPubMed
13.
Cortina MG, Campello AR, Conde JJ, Ois A, Voustianiouk A, Tellez MJ, Cuadrado E, Roquer J: Monocyte count is an underlying marker of lacunar subtype of hypertensive small vessel disease. Eur J Neurol 2008, 15(7):671–676. 10.1111/j.1468-1331.2008.02145.xCrossRefPubMed
14.
van Dijk EJ, Prins ND, Vermeer SE, Vrooman HA, Hofman A, Koudstaal PJ, Breteler MM: C-reactive protein and cerebral small-vessel disease: the Rotterdam Scan Study. Circulation 2005, 112(6):900–905. 10.1161/CIRCULATIONAHA.104.506337CrossRefPubMed
15.
Schiffrin EL: Immune mechanisms in hypertension and vascular injury. Clin Sci (Lond) 2014, 126(4):267–274. 10.1042/CS20130407CrossRef
16.
Bevins RA, Besheer J: Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 2006, 1(3):1306–1311. 10.1038/nprot.2006.205CrossRefPubMed
17.
Gattu M, Pauly JR, Boss KL, Summers JB, Buccafusco JJ: Cognitive impairment in spontaneously hypertensive rats: role of central nicotinic receptors. I. Brain Res 1997, 771(1):89–103. 10.1016/S0006-8993(97)00793-2CrossRefPubMed
18.
Moller K, Stahl T, Boltze J, Wagner DC: Isolation of inflammatory cells from rat brain tissue after stroke. Exp Transl Stroke Med 2012, 4(1):20. 10.1186/2040-7378-4-20CrossRefPubMedPubMedCentral
19.
Shivanandan A, Radenovic A, Sbalzarini IF: MosaicIA: an ImageJ/Fiji plugin for spatial pattern and interaction analysis. BMC Bioinformatics 2013, 14: 349. 10.1186/1471-2105-14-349CrossRefPubMedPubMedCentral
20.
Block ML, Zecca L, Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007, 8(1):57–69. 10.1038/nrn2038CrossRefPubMed
21.
Ley K, Laudanna C, Cybulsky MI, Nourshargh S: Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 2007, 7(9):678–689. 10.1038/nri2156CrossRefPubMed
22.
Chakrabarti S, Chan CK, Jiang Y, Davidge ST: Neuronal nitric oxide synthase regulates endothelial inflammation. J Leukoc Biol 2012, 91(6):947–956. 10.1189/jlb.1011513CrossRefPubMed
23.
Gianaros PJ, Greer PJ, Ryan CM, Jennings JR: Higher blood pressure predicts lower regional grey matter volume: Consequences on short-term information processing. Neuroimage 2006, 31(2):754–765. 10.1016/j.neuroimage.2006.01.003CrossRefPubMedPubMedCentral
24.
Swan GE, Decarli C, Miller BL, Reed T, Wolf PA, Jack LM, Carmelli D: Association of midlife blood pressure to late-life cognitive decline and brain morphology. Neurology 1998, 51(4):986–993. 10.1212/WNL.51.4.986CrossRefPubMed
25.
Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S: Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens 2011, 29(8):1469–1477. 10.1097/HJH.0b013e328347cc17CrossRefPubMed
26.
Mitchell GF: Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage. J Appl Physiol (1985 ) 2008, 105(5):652–1660.
27.
Franklin SS: Arterial stiffness and hypertension: a two-way street? Hypertension 2005, 45(3):349–351. 10.1161/01.HYP.0000157819.31611.87CrossRefPubMed
28.
Fornal M, Wizner B, Cwynar M, Krolczyk J, Kwater A, Korbut RA, Grodzicki T: Association of red blood cell distribution width, inflammation markers and morphological as well as rheological erythrocyte parameters with target organ damage in hypertension. Clin Hemorheol Microcirc 2014, 56(4):325–335.PubMed
29.
Sharp DS, Curb JD, Schatz IJ, Meiselman HJ, Fisher TC, Burchfiel CM, Rodriguez BL, Yano K: Mean red cell volume as a correlate of blood pressure. Circulation 1996, 93(9):1677–1684. 10.1161/01.CIR.93.9.1677CrossRefPubMed
30.
Pantoni L: Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 2010, 9(7):689–701. 10.1016/S1474-4422(10)70104-6CrossRefPubMed
31.
Jalal FY, Yang Y, Thompson J, Lopez AC, Rosenberg GA: Myelin loss associated with neuroinflammation in hypertensive rats. Stroke 2012, 43(4):1115–1122. 10.1161/STROKEAHA.111.643080CrossRefPubMedPubMedCentral
32.
de Groot M, Verhaaren BF, de Boer R, Klein S, Hofman A, van der Lugt A, Ikram MA, Niessen WJ, Vernooij MW: Changes in normal-appearing white matter precede development of white matter lesions. Stroke 2013, 44(4):1037–1042. 10.1161/STROKEAHA.112.680223CrossRefPubMed
33.
Ennaceur A, Delacour J: A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav Brain Res 1988, 31(1):47–59. 10.1016/0166-4328(88)90157-XCrossRefPubMed
34.
Duering M, Zieren N, Herve D, Jouvent E, Reyes S, Peters N, Pachai C, Opherk C, Chabriat H, Dichgans M: Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL. Brain 2011, 134(Pt 8):2366–2375. 10.1093/brain/awr169CrossRefPubMed
35.
den Heijer T, Launer LJ, Prins ND, van Dijk EJ, Vermeer SE, Hofman A, Koudstaal PJ, Breteler MM: Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe. Neurology 2005, 64(2):263–267. 10.1212/01.WNL.0000149641.55751.2ECrossRefPubMed
36.
Sabbatini M, Catalani A, Consoli C, Marletta N, Tomassoni D, Avola R: The hippocampus in spontaneously hypertensive rats: an animal model of vascular dementia? Mech Ageing Dev 2002, 123(5):547–559. 10.1016/S0047-6374(01)00362-1CrossRefPubMed
37.
38.
Linthorst AC, Van den BM, De JW, Versteeg DH: Electrically stimulated [3H]dopamine and [14C]acetylcholine release from nucleus caudatus slices: differences between spontaneously hypertensive rats and Wistar-Kyoto rats. Brain Res 1990, 509(2):266–272. 10.1016/0006-8993(90)90551-LCrossRefPubMed
39.
Stavro GM, Ettenhofer ML, Nigg JT: Executive functions and adaptive functioning in young adult attention-deficit/hyperactivity disorder. J Int Neuropsychol Soc 2007, 13(2):324–334. 10.1017/S1355617707070348CrossRefPubMed
40.
Baker JG, Williams AJ, Ionita CC, Lee-Kwen P, Ching M, Miletich RS: Cerebral small vessel disease: cognition, mood, daily functioning, and imaging findings from a small pilot sample. Dement Geriatr Cogn Dis Extra 2012, 2: 169–179. 10.1159/000333482CrossRefPubMedPubMedCentral
41.
O’Sullivan M, Morris RG, Huckstep B, Jones DK, Williams SC, Markus HS: Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis. J Neurol Neurosurg Psychiatry 2004, 75(3):441–447. 10.1136/jnnp.2003.014910CrossRefPubMedPubMedCentral
42.
Rostrup E, Gouw AA, Vrenken H, van Straaten EC, Ropele S, Pantoni L, Inzitari D, Barkhof F, Waldemar G: The spatial distribution of age-related white matter changes as a function of vascular risk factors–results from the LADIS study. Neuroimage 2012, 60(3):1597–1607. 10.1016/j.neuroimage.2012.01.106CrossRefPubMed
43.
Shi P, ez Freire C, Jun JY, Qi Y, Katovich MJ, Li Q, Sriramula S, Francis J, Sumners C, Raizada MK: Brain microglial cytokines in neurogenic hypertension. Hypertension 2010, 56(2):297–303. 10.1161/HYPERTENSIONAHA.110.150409CrossRefPubMedPubMedCentral
44.
Beard RS, Haines RJ, Wu KY, Reynolds JJ, Davis SM, Elliott JE, Malinin NL, Chatterjee V, Cha BJ, Wu MH, Yuan SY: Non-muscle Mlck is required for beta-catenin- and FoxO1-dependent downregulation of Cldn5 in IL-1beta-mediated barrier dysfunction in brain endothelial cells. J Cell Sci 2014, 127(Pt 8):1840–1853. 10.1242/jcs.144550CrossRefPubMedPubMedCentral
45.
Lim S, Bae E, Kim HS, Kim TA, Byun K, Kim B, Hong S, Im JP, Yun C, Lee B, Lee B, Park SH, Letterio J, Kim SJ: TRAF6 mediates IL-1beta/LPS-induced suppression of TGF-beta signaling through its interaction with the type III TGF-beta receptor. PLoS One 2012, 7(3):e32705. 10.1371/journal.pone.0032705CrossRefPubMedPubMedCentral
46.
Tummala PE, Chen XL, Sundell CL, Laursen JB, Hammes CP, Alexander RW, Harrison DG, Medford RM: Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: a potential link between the renin-angiotensin system and atherosclerosis. Circulation 1999, 100(11):1223–1229. 10.1161/01.CIR.100.11.1223CrossRefPubMed
47.
Rouhl RP, Damoiseaux JG, Lodder J, Theunissen RO, Knottnerus IL, Staals J, Henskens LH, Kroon AA, de Leeuw PW, Tervaert JW, van Oostenbrugge RJ: Vascular inflammation in cerebral small vessel disease. Neurobiol Aging 2012, 33(8):1800–1806. 10.1016/j.neurobiolaging.2011.04.008CrossRefPubMed
48.
Fukuda S, Yasu T, Kobayashi N, Ikeda N, Schmid-Schonbein GW: Contribution of fluid shear response in leukocytes to hemodynamic resistance in the spontaneously hypertensive rat. Circ Res 2004, 95(1):100–108. 10.1161/01.RES.0000133677.77465.38CrossRefPubMed
49.
50.
Senchenkova EY, Russell J, Kurmaeva E, Ostanin D, Granger DN: Role of T lymphocytes in angiotensin II-mediated microvascular thrombosis. Hypertension 2011, 58(5):959–965. 10.1161/HYPERTENSIONAHA.111.173856CrossRefPubMedPubMedCentral
51.
52.
Derecki NC, Cardani AN, Yang CH, Quinnies KM, Crihfield A, Lynch KR, Kipnis J: Regulation of learning and memory by meningeal immunity: a key role for IL-4. J Exp Med 2010, 207(5):1067–1080. 10.1084/jem.20091419CrossRefPubMedPubMedCentral
53.
Kivisakk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, Wu L, Baekkevold ES, Lassmann H, Staugaitis SM, Campbell JJ, Ransohoff RM: Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A 2003, 100(14):8389–8394. 10.1073/pnas.1433000100CrossRefPubMedPubMedCentral
54.
Gunstad J, Benitez A, Hoth KF, Spitznagel MB, McCaffery J, McGeary J, Kakos LS, Poppas A, Paul RH, Jefferson AL, Sweet LH, Cohen RA: P-selectin 1087G/A polymorphism is associated with neuropsychological test performance in older adults with cardiovascular disease. Stroke 2009, 40(9):2969–2972. 10.1161/STROKEAHA.109.553339CrossRefPubMedPubMedCentral
55.
Mathew JP, Podgoreanu MV, Grocott HP, White WD, Morris RW, Stafford-Smith M, Mackensen GB, Rinder CS, Blumenthal JA, Schwinn DA, Newman MF: Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery. J Am Coll Cardiol 2007, 49(19):1934–1942. 10.1016/j.jacc.2007.01.080CrossRefPubMed
56.
Suzuki H, Zweifach BW, Forrest MJ, Schmid-Schonbein GW: Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids. J Leukoc Biol 1995, 57(1):20–26.PubMed
57.
Kossmann S, Schwenk M, Hausding M, Karbach SH, Schmidgen MI, Brandt M, Knorr M, Hu H, Kroller-Schon S, Schonfelder T, Grabbe S, Oelze M, Daiber A, Munzel T, Becker C, Wenzel P: Angiotensin II-induced vascular dysfunction depends on interferon-gamma-driven immune cell recruitment and mutual activation of monocytes and NK-cells. Arterioscler Thromb Vasc Biol 2013, 33(6):1313–1319. 10.1161/ATVBAHA.113.301437CrossRefPubMed
58.
Liu Y, Jacobowitz DM, Barone F, McCarron R, Spatz M, Feuerstein G, Hallenbeck JM, Siren AL: Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats. J Cereb Blood Flow Metab 1994, 14(2):348–352. 10.1038/jcbfm.1994.43CrossRefPubMed
59.
Shao J, Nangaku M, Miyata T, Inagi R, Yamada K, Kurokawa K, Fujita T: Imbalance of T-cell subsets in angiotensin II-infused hypertensive rats with kidney injury. Hypertension 2003, 42(1):31–38. 10.1161/01.HYP.0000075082.06183.4ECrossRefPubMed
60.
van Weel V, Toes RE, Seghers L, Deckers MM, de Vries MR, Eilers PH, Sipkens J, Schepers A, Eefting D, van Hinsbergh VW, van Bockel JH, Quax PH: Natural killer cells and CD4+ T-cells modulate collateral artery development. Arterioscler Thromb Vasc Biol 2007, 27(11):2310–2318. 10.1161/ATVBAHA.107.151407CrossRefPubMed
61.
Calcinaghi N, Wyss MT, Jolivet R, Singh A, Keller AL, Winnik S, Fritschy JM, Buck A, Matter CM, Weber B: Multimodal imaging in rats reveals impaired neurovascular coupling in sustained hypertension. Stroke 2013, 44(7):1957–1964. 10.1161/STROKEAHA.111.000185CrossRefPubMed
62.
la Sala A, Pontecorvo L, Agresta A, Rosano G, Stabile E: Regulation of collateral blood vessel development by the innate and adaptive immune system. Trends Mol Med 2012, 18(8):494–501. 10.1016/j.molmed.2012.06.007CrossRefPubMed
63.
Rosenberg GA: Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 2009, 8(2):205–216. 10.1016/S1474-4422(09)70016-XCrossRefPubMed
64.
Kronenberg G, Lippoldt A, Kempermann G: Two genetic rat models of arterial hypertension show different mechanisms by which adult hippocampal neurogenesis is increased. Dev Neurosci 2007, 29(1–2):124–133. 10.1159/000096217PubMed
65.
Pineda JR, Daynac M, Chicheportiche A, Cebrian-Silla A, Sii FK, Garcia-Verdugo JM, Boussin FD, Mouthon MA: Vascular-derived TGF-beta increases in the stem cell niche and perturbs neurogenesis during aging and following irradiation in the adult mouse brain. EMBO Mol Med 2013, 5(4):548–562. 10.1002/emmm.201202197CrossRefPubMedPubMedCentral
66.
Nordahl CW, Ranganath C, Yonelinas AP, Decarli C, Reed BR, Jagust WJ: Different mechanisms of episodic memory failure in mild cognitive impairment. Neuropsychologia 2005, 43(11):1688–1697. 10.1016/j.neuropsychologia.2005.01.003CrossRefPubMedPubMedCentral
67.
Jonsson M, Edman A, Lind K, Rolstad S, Sjogren M, Wallin A: Apathy is a prominent neuropsychiatric feature of radiological white-matter changes in patients with dementia. Int J Geriatr Psychiatry 2010, 25(6):588–595.PubMed
68.
Lawrence AJ, Patel B, Morris RG, MacKinnon AD, Rich PM, Barrick TR, Markus HS: Mechanisms of cognitive impairment in cerebral small vessel disease: multimodal MRI results from the St George’s cognition and neuroimaging in stroke (SCANS) study. PLoS One 2013, 8(4):e61014. 10.1371/journal.pone.0061014CrossRefPubMedPubMedCentral
69.
Kloppenborg RP, Nederkoorn PJ, Grool AM, Vincken KL, Mali WP, Vermeulen M, van der Graaf Y, Geerlings MI: Cerebral small-vessel disease and progression of brain atrophy: the SMART-MR study. Neurology 2012, 79(20):2029–2036. 10.1212/WNL.0b013e3182749f02CrossRefPubMed
70.
Cordonnier C, Al-Shahi SR, Wardlaw J: Spontaneous brain microbleeds: systematic review, subgroup analyses and standards for study design and reporting. Brain 2007, 130(Pt 8):1988–2003. 10.1093/brain/awl387CrossRefPubMed
71.
Rost NS, Rahman RM, Biffi A, Smith EE, Kanakis A, Fitzpatrick K, Lima F, Worrall BB, Meschia JF, Brown RD Jr, Brott TG, Sorensen AG, Greenberg SM, Furie KL, Rosand J: White matter hyperintensity volume is increased in small vessel stroke subtypes. Neurology 2010, 75(19):1670–1677. 10.1212/WNL.0b013e3181fc279aCrossRefPubMedPubMedCentral
72.
Topakian R, Barrick TR, Howe FA, Markus HS: Blood–brain barrier permeability is increased in normal-appearing white matter in patients with lacunar stroke and leucoaraiosis. J Neurol Neurosurg Psychiatry 2010, 81(2):192–197. 10.1136/jnnp.2009.172072CrossRefPubMed
73.
Papma JM, de Groot M, de Koning I, Mattace-Raso FU, van der Lugt A, Vernooij MW, Niessen WJ, van Swieten JC, Koudstaal PJ, Prins ND, Smits M: Cerebral small vessel disease affects white matter microstructure in mild cognitive impairment. Hum Brain Mapp 2014, 35(6):2836–2851. 10.1002/hbm.22370CrossRefPubMed
74.
Simpson JE, Fernando MS, Clark L, Ince PG, Matthews F, Forster G, O’Brien JT, Barber R, Kalaria RN, Brayne C, Shaw PJ, Lewis CE, Wharton SB: White matter lesions in an unselected cohort of the elderly: astrocytic, microglial and oligodendrocyte precursor cell responses. Neuropathol Appl Neurobiol 2007, 33(4):410–419. 10.1111/j.1365-2990.2007.00828.xCrossRefPubMed
75.
Ekonomou A, Johnson M, Perry RH, Perry EK, Kalaria RN, Minger SL, Ballard CG: Increased neural progenitors in individuals with cerebral small vessel disease. Neuropathol Appl Neurobiol 2012, 38(4):344–353. 10.1111/j.1365-2990.2011.01224.xCrossRefPubMed
Metadata
Title
Spontaneous white matter damage, cognitive decline and neuroinflammation in middle-aged hypertensive rats: an animal model of early-stage cerebral small vessel disease
Authors
Daniel Kaiser
Gesa Weise
Karoline Möller
Johanna Scheibe
Claudia Pösel
Sebastian Baasch
Matthias Gawlitza
Donald Lobsien
Kai Diederich
Jens Minnerup
Alexander Kranz
Johannes Boltze
Daniel-Christoph Wagner
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2014
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-014-0169-8

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