TY  - JOUR
A1  - Niklass, Solveig
A1  - Stoyanov, Stoyan
A1  - Garz, Cornelia
A1  - Bueche, Celine Z.
A1  - Mencl, Stine
A1  - Reymann, Klaus
A1  - Heinze, Hans-Jochen
A1  - Carare, Roxana O.
A1  - Kleinschnitz, Christoph
A1  - Schreiber, Stefanie
T1  - Intravital imaging in spontaneously hypertensive stroke-prone rats-a pilot study
JF  - Experimental & Translational Stroke Medicine
N2  - 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.
KW  - SHRSP
KW  - Intravital imaging
KW  - 2 PM
KW  - CSVD
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121353
VL  - 6
ER  - 
TY  - JOUR
A1  - Huss, André
A1  - Abdelhak, Ahmed
A1  - Mayer, Benjamin
A1  - Tumani, Hayrettin
A1  - Müller, Hans-Peter
A1  - Althaus, Katharina
A1  - Kassubek, Jan
A1  - Otto, Markus
A1  - Ludolph, Albert C.
A1  - Yilmazer-Hanke, Deniz
A1  - Neugebauer, Hermann
T1  - Association of serum GFAP with functional and neurocognitive outcome in sporadic small vessel disease
JF  - Biomedicines
N2  - Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pathological analyses in CSVD revealed a high density of GFAP-immunoreactive fibrillary astrocytic processes in the periventricular white matter and clusters of CHI3L1-immunoreactive astrocytes in the basal ganglia and thalamus. Thus, besides NfL, serum GFAP is a highly promising fluid biomarker of sporadic CSVD, because it does not only correlate with the clinical severity but also correlates with the cognitive function in patients.
KW  - chitinase-3-like protein 1
KW  - GFAP
KW  - neurofilaments
KW  - white matter hyperintensities
KW  - biomarker
KW  - CSVD
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285973
SN  - 2227-9059
VL  - 10
IS  - 8
ER  -