Stases are associated with blood–brain barrier damage and a restricted activation of coagulation in SHRSP

Braun, Holger; Bueche, Celine Zoe; Garz, Cornelia; Oldag, Andreas; Heinze, Hans‐Jochen; Goertler, Michael; Reymann, Klaus G.; Schreiber, Stefanie

doi:10.1016/j.jns.2012.06.013

Cited by 30 publications

(28 citation statements)

References 15 publications

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“…Note the disturbed vascular tone in small vessels with stases indicated by sausage-like wall dilatations, here shown in a striatal trifurcation of arterioles ( D ). E is taken from [25]. A – D Hematoxylin Eosin (HE) staining.…”

Section: Introductionmentioning

confidence: 99%

“…We could demonstrate, that small vessels affected by intravasal erythrocyte accumulations exhibit deposits of plasmaproteins including immunoglobulin G (IgG) within their walls and within the adjacent perivascular parenchyma indicating associated BBB damage at already young ages (Figure 1E & F; [5,25]).…”

Section: Introductionmentioning

confidence: 99%

“…Another important point is the fact that stases are interwoven with aggregated thrombocytes and multimers of the von-Willebrand factor (vWF) (Figure 1G & H; [25]). This suggests that a local, most likely restricted coagulation is one main reason for their occurrence.…”

Section: Introductionmentioning

confidence: 99%

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Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

Schreiber

Bueche

Garz

et al. 2013

Exp & Trans Stroke Med

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118

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Cerebral small vessel disease (CSVD, cerebral microangiopathy) leads to dementia and stroke-like symptoms. Lacunes, white matter lesions (WML) and microbleeds are the main pathological correlates depicted in in-vivo imaging diagnostics. Early studies described segmental arterial wall disorganizations of small penetrating cerebral arteries as the most pronounced underlying histopathology of lacunes. Luminal narrowing caused by arteriolosclerosis was supposed to result in hypoperfusion with WML and infarcts.We have used the model of spontaneously hypertensive stroke-prone rats (SHRSP) for a longitudinal study to elucidate early histological changes in small cerebral vessels. We suggest that endothelial injuries lead to multiple sites with blood brain barrier (BBB) leakage which cause an ongoing damage of the vessel wall and finally resulting in vessel ruptures and microbleeds. These microbleeds together with reactive small vessel occlusions induce overt cystic infarcts of the surrounding parenchyma. Thus, multiple endothelial leakage sites seem to be the starting point of cerebral microangiopathy. The vascular system reacts with an activated coagulatory state to these early endothelial injuries and by this induces the formation of stases, accumulations of erythrocytes, which represent the earliest detectable histological peculiarity of small vessel disease in SHRSP.In this review we focus on the meaning of the BBB breakdown in CSVD and finally discuss possible consequences for clinicians.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

Schreiber

Bueche

Garz

et al. 2013

Exp & Trans Stroke Med

Self Cite

118

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“…The vWF was adherent at the small vessel walls (Figure 4A-C) or was detected within the lumen of the small vessels where it was often associated with the occurrence of intravasal erythrocyte accumulations [8]. IgG, indicative for BBB-disturbances [10,13], was found to be accumulated in the small vessel walls as well as in the parenchyma adjacent to the capillaries and arterioles (Figure 5A & B; [8,9]).…”

Section: Resultsmentioning

confidence: 99%

“…Recently we described in Spontaneously Hypertensive Stroke-Prone Rats (SHRSP) the cerebral small vessel disease (CSVD) as a cascade starting from capillary and arteriolar erythrocyte accumulations we referred to as stases and blood–brain-barrier (BBB)-damage leading via microbleeds to secondary thromboses and infarctions [8,9]. Now, we were interested whether a long-term treatment of these rats with NAC influences the development of CSVD.…”

Section: Introductionmentioning

confidence: 99%

NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases - a randomized controlled study

Bueche

Garz

Kropf

et al. 2013

Exp & Trans Stroke Med

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BackgroundN-Acetylcystein (NAC) reduces the reperfusion injury and infarct size in experimental macroangiopathic stroke. Here we now investigate the impact of NAC on the development of the histopathology of microangiopathic cerebrovascular disease including initial intravasal erythrocyte accumulations, blood–brain-barrier (BBB)-disturbances, microbleeds and infarcts.MethodsSpontaneously Hypertensive Stroke-Prone Rats (SHRSP) were treated with NAC (12 mg/kg body weight, daily oral application for three to 30 weeks) and compared to untreated SHRSP. In all rats the number of microbleeds, thromboses, infarcts and stases were quantified by HE-staining. Exemplary brains were stained against von Willebrand factor (vWF), IgG, Glutathione and GFAP.ResultsNAC animals exhibited significant more microbleeds, a greater number of vessels with BBB-disturbances, but also an elevation of Glutathione-levels in astrocytes surrounding small vessels. NAC-treatment reduced the numbers of thromboses, infarcts and arteriolar stases.ConclusionsNAC reduces the frequency of thromboses and infarcts to the expense of an increase of small microbleeds in a rat model of microangiopathic cerebrovascular disease. We suppose that NAC acts via an at least partial inactivation of vWF resulting in an insufficient sealing of initial endothelial injury leading to more small microbleeds. By elevating Glutathione-levels NAC most likely exerts a radical scavenger function and protects small vessels against extended ruptures and subsequent infarcts. Finally, it reveals that stases are mainly caused by endothelial injuries and restricted thromboses.

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Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

Hua

et al. 2017

Biomedical Chromatography

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A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao-Hong-Si-Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute blood stasis syndrome was induced by placing the rats in ice-cold water following two injections with epinephrine. The hemorheological indicators [whole blood viscosity (WBV) and plasma viscosity (PV)] and the blood coagulation indicators [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l-glutamate, l-phenylalanine, N-acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.

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Stases are associated with blood–brain barrier damage and a restricted activation of coagulation in SHRSP

Cited by 30 publications

References 15 publications

Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

Blood brain barrier breakdown as the starting point of cerebral small vessel disease? - New insights from a rat model

NAC changes the course of cerebral small vessel disease in SHRSP and reveals new insights for the meaning of stases - a randomized controlled study

Effects of Tao‐Hong‐Si‐Wu decoction on acute blood stasis in rats based on a LC‐Q/TOF‐MS metabolomics and network approach

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