12135
2014
eng
1
6
article
1
2015-10-28
--
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Intravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study
Background
There is growing evidence that endothelial failure and subsequent blood brain barrier (BBB) breakdown initiate cerebral small vessel disease (CSVD) pathology. In spontaneously hypertensive stroke-prone rats (SHRSP) endothelial damage is indicated by intraluminal accumulations of erythrocytes (erythrocyte thrombi) that are not observed with current magnetic resonance imaging techniques. Two-photon microscopy (2 PM) offers the potential for real-time direct detection of the small vasculature. Thus, within this pilot study we investigated the sensitivity of 2 PM to detect erythrocyte thrombi expressing initiating CSVD phenomena in vivo.
Methods
Eight SHRSP and 13 Wistar controls were used for in vivo imaging and subsequent histology with haematoxylin-eosin (HE). For 2 PM, cerebral blood vessels were labeled by fluorescent Dextran (70 kDa) applied intraorbitally. The correlation between vascular erythrocyte thrombi observed by 2 PM and HE-staining was assessed. Artificial surgical damage and parenchymal Dextran distribution were analyzed postmortem.
Results
Dextran was distributed within the small vessel walls and co-localized with IgG.
Artificial surgical damage was comparable between SHRSP and Wistar controls and mainly affected the small vasculature. In fewer than 20% of animals there was correlation between erythrocyte thrombi as observed with 2 PM and histologically with HE.
Conclusions
Contrary to our initial expectations, there was little agreement between intravital 2 PM imaging and histology for the detection of erythrocyte thrombi. Two-photon microscopy is a valuable technique that complements but does not replace the value of conventional histology.
Experimental & Translational Stroke Medicine
10.1186/2040-7378-6-1
24461046
urn:nbn:de:bvb:20-opus-121353
Experimental & Translational Stroke Medicine 2014, 6:1. doi:10.1186/2040-7378-6-1
Solveig Niklass
Stoyan Stoyanov
Cornelia Garz
Celine Z. Bueche
Stine Mencl
Klaus Reymann
Hans-Jochen Heinze
Roxana O. Carare
Christoph Kleinschnitz
Stefanie Schreiber
eng
uncontrolled
SHRSP
eng
uncontrolled
Intravital imaging
eng
uncontrolled
2 PM
eng
uncontrolled
CSVD
Medizin und Gesundheit
open_access
Neurochirurgische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/12135/045_Niklass_Experimental_&_Translational_Stroke_Medicine.pdf
9705
2013
eng
article
1
--
--
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Early microvascular dysfunction in cerebral small vessel disease is not detectable on 3.0 Tesla magnetic resonance imaging: a longitudinal study in spontaneously hypertensive stroke-prone rats
Background
Human cerebral small vessel disease (CSVD) has distinct histopathologic and imaging findings in its advanced stages. In spontaneously hypertensive stroke-prone rats (SHRSP), a well-established animal model of CSVD, we recently demonstrated that cerebral microangiopathy is initiated by early microvascular dysfunction leading to the breakdown of the blood–brain barrier and an activated coagulatory state resulting in capillary and arteriolar erythrocyte accumulations (stases). In the present study, we investigated whether initial microvascular dysfunction and other stages of the pathologic CSVD cascade can be detected by serial magnetic resonance imaging (MRI).
Findings
Fourteen SHRSP and three control (Wistar) rats (aged 26–44 weeks) were investigated biweekly by 3.0 Tesla (3 T) MRI. After perfusion, brains were stained with hematoxylin–eosin and histology was correlated with MRI data. Three SHRSP developed terminal CSVD stages including cortical, hippocampal, and striatal infarcts and macrohemorrhages, which could be detected consistently by MRI. Corresponding histology showed small vessel thromboses and increased numbers of small perivascular bleeds in the infarcted areas. However, 3 T MRI failed to visualize intravascular erythrocyte accumulations, even in those brain regions with the highest densities of affected vessels and the largest vessels affected by stases, as well as failing to detect small perivascular bleeds.
Conclusion
Serial MRI at a field strength of 3 T failed to detect the initial microvascular dysfunction and subsequent small perivascular bleeds in SHRSP; only terminal stages of cerebral microangiopathy were reliably detected. Further investigations at higher magnetic field strengths (7 T) using blood- and flow-sensitive sequences are currently underway.
Experimental & Translational Stroke Medicine
10.1186/2040-7378-5-8
http://www.etsmjournal.com/content/5/1/8
urn:nbn:de:bvb:20-opus-97056
In: Experimental & Translational Stroke Medicine (2013) 5: 8, doi:10.1186/2040-7378-5-8
Christoph Kleinschnitz
Stine Mencl
Cornelia Garz
Solveig Niklass
Holger Braun
Eva Göb
György Homola
Hans-Jochen Heinze
Klaus G. Reymann
Stefanie Schreiber
eng
uncontrolled
Cerebral small vessel disease
eng
uncontrolled
SHRSP
eng
uncontrolled
MRI
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Strahlentherapie
Neurologische Klinik und Poliklinik
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9705/Kleinschnitz_2040-7378-5-8.pdf
17049
2017
eng
e0182822
8
12
article
1
2018-10-29
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Hypercholesterolemia induced cerebral small vessel disease
Background
While hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr\(^{−/-}\) mouse model.
Methods
We used Ldlr\(^{−/-}\) mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr\(^{−/-}\) mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds.
Results
We found a significant increase in the number of erythrocyte stases in 6 months old Ldlr\(^{−/-}\) mice compared to all other groups (P < 0.05). Ldlr\(^{−/-}\) animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr\(^{−/-}\) mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr\(^{−/-}\) mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions.
Conclusions
In Ldlr\(^{−/-}\) mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr\(^{−/-}\) mice appear to be an adequate animal model for research into CSVD.
PLoS ONE
10.1371/journal.pone.0182822
28796818
urn:nbn:de:bvb:20-opus-170493
PLoS ONE 12(8):e0182822 (2017). DOI: 10.1371/journal.pone.0182822
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Peter Kraft
Michael K. Schuhmann
Cornelia Garz
Solveig Jandke
Daniela Urlaub
Stine Mencl
Alma Zernecke
Hans-Jochen Heinze
Roxana O. Carare
Christoph Kleinschnitz
Stefanie Schreiber
eng
uncontrolled
hypercholesterolemia
eng
uncontrolled
cerebral small vessel disease
eng
uncontrolled
mouse model
eng
uncontrolled
histology
Medizin und Gesundheit
open_access
Institut für Klinische Biochemie und Pathobiochemie
Neurologische Klinik und Poliklinik
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17049/043_Kraft_PLOS-ONE.pdf