140 research outputs found
Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits
Background: The role of endothelin-1 (ET-1) and nitric oxide (NO) as two important mediators in the development of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is controversial. The objective of this study was to determine whether local levels of ET-1 and NO in cerebral arterial plasma and/or in cerebrospinal fluid (CSF) are associated with the occurrence of CVS after SAH. Methods: CVS was induced using the one-haemorrhage rabbit model and confirmed by digital subtraction angiography of the rabbits' basilar artery on day 5. Prior to sacrifice, local CSF and basilar arterial plasma samples were obtained by a transclival approach to the basilar artery. Systemic arterial plasma samples were obtained. ET-1 levels were determined by immunometric technique (pg/ml ± SEM) and total nitrate/nitrite level spectrophotometrically (µmol/l ± SEM). Findings: Angiographic CVS was documented after SAH induction (n = 12, P < 0.05). The ET-1 level in CSF was significantly elevated by 27.3% to 0.84 ± 0.08pg/ml in SAH animals (n = 7) in comparison to controls (0.66 ± 0.04pg/ml, n = 7, P < 0.05). There was no significant difference in ET-1 levels in systemic and basilar arterial plasma samples of SAH animals compared to controls. A significant lack of local NO metabolites was documented in basilar arterial plasma after SAH (36.8 ± 3.1µmol/l, n = 6) compared to controls (61.8 ± 6.2µmol/l, n = 6, P < 0.01). Conclusion: This study demonstrates that an elevated ET-1 level in CSF and local lack of NO in the basilar arterial plasma samples are associated with CVS after experimental SA
Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo
Objective: Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo. Methods: New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 μg/μl (0.5 μl/h) or nimodipine at 0.2 μg/μl (10 μl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day0 to day5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements. Results: Atotal of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85 ± 2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93 ± 5.2%, n = 11) and nimodipine (SAH/nimodipine group: 0.55 ± 2.66%, n = 9). There was no significant difference between the treatment groups and controls in prevention of CVS. Conclusions: This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal mode
Norepinephrine-induced hypertension dilates vasospastic basilar artery after subarachnoid haemorrhage in rabbits
Background: Vasopressor-induced hypertension is routinely indicated for prevention and treatment of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). Mechanisms underlying patients' clinical improvement during vasopressor-induced hypertension remain incompletely understood. The aim of this study was to evaluate angiographic effects of normovolaemic Norepinephrine (NE)-induced hypertension therapy on the rabbit basilar artery (BA) after SAH. Methods: Cerebral vasospasm was induced using the one-haemorrhage rabbit model; sham-operated animals served as controls. Five days later the animals underwent follow-up angiography prior to and during NE-induced hypertension. Changes in diameter of the BA were digitally calculated in mean µm ± SEM (standard error of mean). Findings: Significant CVS of 14.2% was documented in the BA of the SAH animals on day 5 compared to the baseline angiogram on day 0 (n = 12, p  0.05). During systemic administration of NE, mean arterial pressure increased from 70.0 ± 1.9mmHg to 136.0 ± 2.1mmHg in the SAH group (n = 12, p < 0.001) and from 72.0 ± 3.1 to 137.8 ± 1.3 in the control group (n = 12, p < 0.001). On day 5 after SAH, a significant dilatation of the BA in response to norepinephrine could be demonstrated in both groups. The diameter of the BA in the SAH group increased from 640.5 ± 17.5 µm to 722.5 ± 23.7 µm (n = 12, p < 0.05; ). In the control group the diameter increased from 716.8 ± 15.5 µm to 779.9 ± 24.1 µm (n = 12, p < 0.05). Conclusion: This study demonstrated that NE-induced hypertension causes angiographic dilatation of the BA in the SAH rabbit model. Based on these observations, it can be hypothesised that clinical improvement during vasopressor-induced hypertension therapy after SAH might be explained with cerebral vasodilatation mechanisms that lead to improvement of cerebral blood flo
Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo
OBJECTIVE: Intrathecal bolus administration of nitric oxide donors and calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Intrathecal continuous administration of these substances for CVS prevention has not been extensively evaluated. This study compared the efficacy of continuous intrathecal infusions of the NO donor glyceroltrinitrate and nimodipine in preventing delayed CVS associated with SAH in an animal model in vivo. METHODS: New Zealand White rabbits were randomly assigned to six groups: no SAH/NaCl, no SAH/NO, no SAH/nimodipine, SAH/NaCl, SAH/NO, or SAH/nimodipine. Glyceroltrinitrate (GTN) at 0.5 microg/microl (0.5 microl/h) or nimodipine at 0.2 microg/microl (10 microl/h) or NaCl was continuously infused into the cisterna magna via an Alzet osmotic pump from day 0 to day 5 after injection of 1.0 ml autologous blood. The magnitude of spasm in the basilar artery was determined by comparison of pre- and posttreatment angiography and was calculated as proportional change in intraluminal diameter based on automatic measurements. RESULTS: A total of 55 experiments and 110 angiograms were performed. SAH was associated with vasoconstriction of the basilar artery (SAH/NaCl group 19.85+/-2.94%). Continuous intrathecal injection of GTN and nimodipine prevented SAH-induced CVS. There was significant prevention of CVS in animals treated with GTN (SAH/NO group 5.93+/-5.2%, n=11) and nimodipine (SAH/nimodipine group: 0.55+/-2.66%, n=9). There was no significant difference between the treatment groups and controls in prevention of CVS. CONCLUSIONS: This study demonstrates that prophylactic continuous intrathecal administration of either GTN or nimodipine equally prevents SAH-associated CVS in an animal model
Rapid, label-free classification of glioblastoma differentiation status combining confocal Raman spectroscopy and machine learning
Label-free identification of tumor cells using spectroscopic assays has emerged as a technological innovation with a proven ability for rapid implementation in clinical care. Machine learning facilitates the
optimization of processing and interpretation of extensive data, such as various spectroscopy data
obtained from surgical samples. The here-described preclinical work investigates the potential of
machine learning algorithms combining confocal Raman spectroscopy to distinguish non-differentiated
glioblastoma cells and their respective isogenic differentiated phenotype by means of confocal ultra-rapid
measurements. For this purpose, we measured and correlated modalities of 1146 intracellular single-point
measurements and sustainingly clustered cell components to predict tumor stem cell existence. By
further narrowing a few selected peaks, we found indicative evidence that using our computational
imaging technology is a powerful approach to detect tumor stem cells in vitro with an accuracy of 91.7%
in distinct cell compartments, mainly because of greater lipid content and putative different protein structures. We also demonstrate that the presented technology can overcome intra- and intertumoral cellular
heterogeneity of our disease models, verifying the elevated physiological relevance of our applied disease
modeling technology despite intracellular noise limitations for future translational evaluatio
Artificial-intelligence-based molecular classification of diffuse gliomas using rapid, label-free optical imaging
Molecular classification has transformed the management of brain tumors by
enabling more accurate prognostication and personalized treatment. However,
timely molecular diagnostic testing for patients with brain tumors is limited,
complicating surgical and adjuvant treatment and obstructing clinical trial
enrollment. In this study, we developed DeepGlioma, a rapid ( seconds),
artificial-intelligence-based diagnostic screening system to streamline the
molecular diagnosis of diffuse gliomas. DeepGlioma is trained using a
multimodal dataset that includes stimulated Raman histology (SRH); a rapid,
label-free, non-consumptive, optical imaging method; and large-scale, public
genomic data. In a prospective, multicenter, international testing cohort of
patients with diffuse glioma () who underwent real-time SRH imaging, we
demonstrate that DeepGlioma can predict the molecular alterations used by the
World Health Organization to define the adult-type diffuse glioma taxonomy (IDH
mutation, 1p19q co-deletion and ATRX mutation), achieving a mean molecular
classification accuracy of . Our results represent how
artificial intelligence and optical histology can be used to provide a rapid
and scalable adjunct to wet lab methods for the molecular screening of patients
with diffuse glioma.Comment: Paper published in Nature Medicin
The effect of tracheotomy on drug consumption in patients with acute aneurysmal subarachnoid hemorrhage: an observational study
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