a-volumetric-method-for-quantification-cerebral-vasospasm-murine

A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage

Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke. Cerebral vasospasm that occurs in the aftermath of the bleeding is an important factor ...

multicolor-3d-printing-of-complex-intracranial-tumors-in-neurosurgery

Multicolor 3D Printing of Complex Intracranial Tumors in Neurosurgery

Three-dimensional (3D) printing technologies offer the possibility of visualizing patient-specific pathologies in a physical model of correct dimensions. ...

analysis-cerebral-vasospasm-murine-model-subarachnoid-hemorrhage-with

Analysis of Cerebral Vasospasm in a Murine Model of Subarachnoid Hemorrhage with High Frequency Transcranial Duplex Ultrasound

Cerebral vasospasm that occurs in the weeks after subarachnoid hemorrhage, a type of hemorrhagic stroke, contributes to delayed cerebral ischemia. A ...

Medical Center of the Johannes Gutenberg - University

University Medical Center of the Johannes Gutenberg University Mainz, Germany

University Medical Center of the Johannes Gutenberg-University of Mainz

Semisynthetic collagen matrices are promising duraplasty grafts with low risk of cerebrospinal fluid (CSF) fistulas, good tissue integration and minor foreign body reaction. The present study investigates the efficacy and biocompatibility of a novel semisynthetic bilayered collagen matrix (BCM, B. Braun Aesculap) as dural onlay graft for duraplasty.

Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen matrix as a dural onlay graft in a large animal model.

Transcranial Doppler ultrasound (TCD) is a standard method for bedside vasospasm monitoring after subarachnoid hemorrhage (SAH). Image guidance has previously been shown to reduce intra- and interobserver variability of this method. The aim of the present study was to compare image-guided and conventional TCD in vasospasm monitoring after SAH.

Image-guided transcranial Doppler sonography for monitoring of vasospasm after subarachnoid hemorrhage.

Clinical studies on subarachnoid hemorrhage (SAH) have shown discrepancies between large vessel vasospasm, cerebral perfusion, and clinical outcome. We set out to analyze the contribution of large vessel vasospasm to impaired cerebral perfusion and neurological impairment in a murine model of SAH. SAH was induced in C57BL/6 mice by endovascular filament perforation. Vasospasm was analyzed with microcomputed tomography, cortical perfusion by laser SPECKLE contrast imaging, and functional impairment with a quantitative neuroscore. SAH animals developed large vessel vasospasm, as shown by significantly lower vessel volumes of a 2.5-mm segment of the left middle cerebral artery (MCA) (SAH 5.6 ± 0.6 nL, sham 8.3 ± 0.5 nL, p < 0.01). Induction of SAH significantly reduced cerebral perfusion of the corresponding left MCA territory compared to values before SAH, which only recovered partly (SAH vs. sham, 15 min 35.7 ± 3.1 vs. 101.4 ± 10.2%, p < 0.01; 3 h, 85.0 ± 8.6 vs. 121.9 ± 13.4, p < 0.05; 24 h, 75.3 ± 4.6 vs. 110.6 ± 11.4%, p < 0.01; 72 h, 81.8 ± 4.8 vs. 108.5 ± 14.5%, n.s.). MCA vessel volume did not correlate significantly with MCA perfusion after 72 h (r = 0.34, p = 0.25). Perfusion correlated moderately with neuroscore (24 h: r = - 0.58, p < 0.05; 72 h: r = - 0.44, p = 0.14). There was no significant correlation between vessel volume and neuroscore after 72 h (r = - 0.21, p = 0.50). In the murine SAH model, cerebral hypoperfusion occurs independently of large vessel vasospasm. Neurological outcome is associated with cortical hypoperfusion rather than large vessel vasospasm.

Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage.

Cerebral hypoperfusion in the first hours after subarachnoid haemorrhage (SAH) is a major determinant of poor neurological outcome. However, the underlying pathophysiology is only partly understood. Here we induced neutropenia in C57BL/6N mice by anti-Ly6G antibody injection, induced SAH by endovascular filament perforation, and analysed cerebral cortical perfusion with laser SPECKLE contrast imaging to investigate the role of neutrophils in mediating cerebral hypoperfusion during the first 24 h post-SAH. SAH induction significantly increased the intracranial pressure (ICP), and significantly reduced the cerebral perfusion pressure (CPP). At 3 h after SAH, ICP had returned to baseline and CPP was similar between SAH and sham mice. However, in SAH mice with normal neutrophil counts cortical hypoperfusion persisted. Conversely, despite similar CPP, cortical perfusion was significantly higher at 3 h after SAH in mice with neutropenia. The levels of 8-iso-prostaglandin-F2α in the subarachnoid haematoma increased significantly at 3 h after SAH in animals with normal neutrophil counts indicating oxidative stress, which was not the case in neutropenic SAH animals. These results suggest that neutrophils are important mediators of cortical hypoperfusion and oxidative stress early after SAH. Targeting neutrophil function and neutrophil-induced oxidative stress could be a promising new approach to mitigate cerebral hypoperfusion early after SAH.

Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage.

A considerable number of patients with subarachnoid hemorrhage (SAH) develop vasospasms of the infratentorial arteries. Transcranial Doppler sonography (TCD) is used to screen for vasospasm. In this study, we used a technical modification that combines TCD with an image guidance device that the operator can use to navigate to the ultrasonic window and to predefined intracranial vascular targets. Our aim was to analyze the feasibility, spatial precision, and spatial reproducibility of serial image-guided TCD of infratentorial and-for comparison-supratentorial arteries in the clinical setting of monitoring for vasospasm after SAH.

Image-Guided Transcranial Doppler Ultrasound for Monitoring Posthemorrhagic Vasospasms of Infratentorial Arteries: A Feasibility Study.

 Computed tomography angiography (CTA) is frequently used with computed tomography perfusion imaging (CTP) to evaluate whether endovascular vasospasm treatment is indicated for subarachnoid hemorrhage patients with delayed cerebral ischemia. However, objective parameters for CTA evaluation are lacking. In this study, we used an automated, investigator-independent, digital method to detect vasospasm, and we evaluated whether the method could predict the need for subsequent endovascular vasospasm treatment.  We retrospectively reviewed the charts and analyzed imaging data for 40 consecutive patients with subarachnoid hemorrhages. The cerebrovascular trees were digitally reconstructed from CTA data, and vessel volume and the length of the arteries of the circle of Willis and their peripheral branches were determined. Receiver operating characteristic curve analysis based on a comparison with digital subtraction angiographies was used to determine volumetric thresholds that indicated severe vasospasm for each vessel segment.  The automated threshold-based volumetric evaluation of CTA data was able to detect severe vasospasm with high sensitivity and negative predictive value for predicting cerebral hypoperfusion on CTP, although the specificity and positive predictive value were low. Combining the automated detection of vasospasm on CTA and cerebral hypoperfusion on CTP was superior to CTP or CTA alone in predicting endovascular vasospasm treatment within 24 h after the examination.  This digital volumetric analysis of the cerebrovascular tree allowed the objective, investigator-independent detection and quantification of vasospasms. This method could be used to standardize diagnostics and the selection of subarachnoid hemorrhage patients with delayed cerebral ischemia for endovascular diagnostics and possible interventions.

Automated Grading of Cerebral Vasospasm to Standardize Computed Tomography Angiography Examinations After Subarachnoid Hemorrhage.

Cerebral hypoperfusion is a key factor for determining the outcome after subarachnoid hemorrhage (SAH). A subset of SAH patients develop neurogenic stress cardiomyopathy (NSC), but it is unclear to what extent cerebral hypoperfusion is influenced by cardiac dysfunction after SAH. The aims of this study were to examine the association between cardiac function and cerebral perfusion in a murine model of SAH and to identify electrocardiographic and echocardiographic signs indicative of NSC. We quantified cortical perfusion by laser SPECKLE contrast imaging, and myocardial function by serial high-frequency ultrasound imaging, for up to 7 days after experimental SAH induction in mice by endovascular filament perforation. Cortical perfusion decreased significantly whereas cardiac output and left ventricular ejection fraction increased significantly shortly post-SAH. Transient pathological ECG and echocardiographic abnormalities, indicating NSC (right bundle branch block, reduced left ventricular contractility), were observed up to 3 h post-SAH in a subset of model animals. Cerebral perfusion improved over time after SAH and correlated significantly with left ventricular end-diastolic volume at 3, 24, and 72 h. The murine SAH model is appropriate to experimentally investigate NSC. We conclude that in addition to cerebrovascular dysfunction, cardiac dysfunction may significantly influence cerebral perfusion, with LVEDV presenting a potential parameter for risk stratification.

Correlation of cardiac function and cerebral perfusion in a murine model of subarachnoid hemorrhage.

 Unruptured Intracranial Aneurysm (UIA) Treatment Score (UIATS) and PHASES score are used to inform treatment decision making for UIAs (treatment or observation). We assessed the ability of the scoring systems to discriminate between ruptured aneurysms and UIAs in a subarachnoid hemorrhage (SAH) cohort with multiple aneurysms.  We retrospectively applied PHASES and UIATS scoring to the aneurysms of 40 consecutive patients with SAH and multiple intracranial aneurysms.  PHASES score discriminated better between ruptured aneurysms and UIAs than UIATS. PHASES scores and the difference between the UIATS subscores were higher for ruptured aneurysms compared with UIAs, which reached significance for the PHASES score. PHASES score estimated a low 5-year rupture risk in a larger proportion of the UIAs (≤0.7% in 62.3%, ≤1.7% in 98.4%) than of the ruptured aneurysms (≤0.7% in 22.5%, ≤1.7% in 82.5%). In the 40 ruptured aneurysms, UIATS provided recommendation for treatment in 11 (27.5%), conservative management in 14 (35.0%), and was inconclusive in 15 cases (37.5%). In the 61 UIAs, UIATS recommended treatment in 16 (26.2%), conservative management in 29 (47.5%), and was inconclusive in 16 (26.2%) cases.  Similar to previous SAH cohorts, a significant proportion of the ruptured aneurysms exhibited a low-rupture risk. Nevertheless, PHASES score discriminated between ruptured aneurysms and UIAs in our cohort; the lower discriminatory power of UIATS was due to high weights of aneurysm-independent factors. We recommend careful integration of the scores for individual decision making. Large-scale prospective trials are required to establish score-based treatment strategies for UIAs.

Comparison of Unruptured Intracranial Aneurysm Treatment Score and PHASES Score in Subarachnoid Hemorrhage Patients With Multiple Intracranial Aneurysms.

ArticleTotal : 3	Year
Publication title Cited by 4	2018
Publication title Cited by 21	2020
Publication title	2021

Article	Year
Evaluation of efficacy and biocompatibility of a novel semisynthetic collagen matrix as a dural onlay graft in a large animal model. Acta neurochirurgica\| PubMed ID: 21739175	2011
Image-guided transcranial Doppler sonography for monitoring of vasospasm after subarachnoid hemorrhage. Clinical neurology and neurosurgery\| PubMed ID: 27062685	2016
Large Vessel Vasospasm Is Not Associated with Cerebral Cortical Hypoperfusion in a Murine Model of Subarachnoid Hemorrhage. Translational stroke research\| PubMed ID: 30003500	2018
Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage. Scientific reports\| PubMed ID: 31186479	2019
Image-Guided Transcranial Doppler Ultrasound for Monitoring Posthemorrhagic Vasospasms of Infratentorial Arteries: A Feasibility Study. World neurosurgery\| PubMed ID: 31678314	2020
Automated Grading of Cerebral Vasospasm to Standardize Computed Tomography Angiography Examinations After Subarachnoid Hemorrhage. Frontiers in neurology\| PubMed ID: 32082241	2020
Correlation of cardiac function and cerebral perfusion in a murine model of subarachnoid hemorrhage. Scientific reports\| PubMed ID: 33558609	2021
Comparison of Unruptured Intracranial Aneurysm Treatment Score and PHASES Score in Subarachnoid Hemorrhage Patients With Multiple Intracranial Aneurysms. Frontiers in neurology\| PubMed ID: 33897586	2021

Axel Neulen

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