scholarly journals Involvement of neutrophils in machineries underlying the rupture of intracranial aneurysms in rats

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mika Kushamae ◽  
Haruka Miyata ◽  
Manabu Shirai ◽  
Kampei Shimizu ◽  
Mieko Oka ◽  
...  

AbstractSubarachnoid hemorrhage due to rupture of an intracranial aneurysm has a quite poor prognosis after the onset of symptoms, despite the modern technical advances. Thus, the mechanisms underlying the rupture of lesions should be clarified. To this end, we obtained gene expression profile data and identified the neutrophil-related enriched terms in rupture-prone lesions using Gene Ontology analysis. Next, to validate the role of neutrophils in the rupture of lesions, granulocyte-colony stimulating factor (G-CSF) was administered to a rat model, in which more than half of induced lesions spontaneously ruptured, leading to subarachnoid hemorrhage. As a result, G-CSF treatment not only increased the number of infiltrating neutrophils, but also significantly facilitated the rupture of lesions. To clarify the mechanisms of how neutrophils facilitate this rupture, we used HL-60 cell line and found an enhanced collagenolytic activity, corresponding to matrix metalloproteinase 9 (MMP9), upon inflammatory stimuli. The immunohistochemical analyses revealed the accumulation of neutrophils around the site of rupture and the production of MMP9 from these cells in situ. Consistently, the collagenolytic activity of MMP9 could be detected in the lysate of ruptured lesions. These results suggest the crucial role of neutrophils to the rupture of intracranial aneurysms; implying neutrophils as a therapeutic or diagnostic target candidate.

2019 ◽  
Author(s):  
Mika Kushamae ◽  
Haruka Miyata ◽  
Manabu Shirai ◽  
Kampei Shimizu ◽  
Mieko Oka ◽  
...  

Abstract Background: Subarachnoid hemorrhage due to rupture of an intracranial aneurysm (IA) has quite a poor prognosis once after the onset despite of the modern technical advancement. The development of a novel therapeutic modality to prevent rupture or a diagnostic method to stratify dangerous lesions from many stable ones is thus mandatory for social health. To this end, mechanisms underlying rupture of lesions should be clarified. Methods: We and others have developed the rat model in which induced IAs spontaneously rupture resulting in subarachnoid hemorrhage. To clarify molecular cascades regulating rupture, we obtained gene expression profile data from rupture-prone lesions and revealed the enrichment of neutrophil-related terms in rupture-prone lesions by Gene Ontology analysis. Next, to validate a role of neutrophils in rupture of lesions, G-CSF was administered to a rat model. Results: As a result, G-CSF treatment not only increased number of neutrophils infiltrating in lesions but also significantly facilitated rupture of the lesions without increase the incidence. To clarify mechanisms how neutrophils facilitate rupture of IAs, we used HL-60 cell line and found that inflammatory stimuli enhanced the collagenolytic activity of MMP9. Immunohistochemical study using IA lesions from a rat model identified neutrophils as a major type of cells producing MMP9 around a site of rupture and consistently the collagenolytic activity of MMP9 was detected in ruptured lesions. Conclusions: These results combined together suggest the crucial role of neutrophil to rupture of IAs and also propose the potential of this type of cells as a candidate of therapeutic or diagnostic targets.


2018 ◽  
Vol 9 (1) ◽  
pp. 150 ◽  
Author(s):  
Gustavo Pradilla ◽  
JackW Barrow ◽  
Nefize Turan ◽  
Pasang Wangmo ◽  
AnilK Roy

2019 ◽  
Vol 47 (6) ◽  
pp. E20 ◽  
Author(s):  
Brian M. Howard ◽  
Ranliang Hu ◽  
Jack W. Barrow ◽  
Daniel L. Barrow

Intracranial aneurysms confer the risk of subarachnoid hemorrhage (SAH), a potentially devastating condition, though most aneurysms will remain asymptomatic for the lifetime of the patient. Imaging is critical to all stages of patient care for those who harbor an unruptured intracranial aneurysm (UIA), including to establish the diagnosis, to determine therapeutic options, to undertake surveillance in patients who elect not to undergo treatment or whose aneurysm(s) portends such a low risk that treatment is not indicated, and to perform follow-up after treatment. Neuroimaging is equally as important in patients who suffer an SAH. DSA remains the reference standard for imaging of intracranial aneurysms due to its high spatial and temporal resolution. As noninvasive imaging technology, such as CTA and MRA, improves, the diagnostic accuracy of such tests continues to increasingly approximate that of DSA. In cases of angiographically negative SAH, imaging protocols are necessary not only for diagnosis but also to search for an initially occult vascular lesion, such as a thrombosed, ruptured aneurysm that might be detected in a delayed fashion. Given the crucial role of neuroimaging in all aspects of care for patients with UIAs and SAH, it is incumbent on those who care for these patients, including cerebrovascular neurosurgeons, interventional neurologists and neuroradiologists, and diagnostic radiologists and neurointensivists, to understand the role of imaging in this disease and how individual members of the multispecialty team use imaging to ensure best practices to deliver cutting-edge care to these often complex cases. This review expounds on the role of imaging in the management of UIAs and ruptured intracranial aneurysms and in the workup of angiographically negative subarachnoid hemorrhage.


1995 ◽  
Vol 269 (3) ◽  
pp. H1009-H1015 ◽  
Author(s):  
M. Zuccarello ◽  
A. Romano ◽  
M. Passalacqua ◽  
R. M. Rapoport

The purpose of this study was to test whether endothelium-dependent relaxation is decreased during acute vasospasm following subarachnoid hemorrhage (SAH) and the mechanism underlying the decrease. Basilar artery in situ was 35% constricted 3 days following injection of autologous arterial blood into the rabbit cisterna magna compared with vessels from control rabbits. In situ suffusion with the endothelium-dependent relaxant, acetylcholine (ACh; 10 microM), relaxed resting and serotonin (5-HT)-contracted control vessels but not vasospastic and 5-HT-contracted vasospastic vessels. In contrast, the relaxant potency and efficacy of ACh was similar in control and vasospastic vessels contracted with 5-HT in vitro. In situ suffusion with the ETA-receptor antagonist, BQ-123 (1 microM), reversed the vasospasm by 51% and restored the magnitude of ACh relaxation of vasospastic and 5-HT-contracted vasospastic vessels to that of controls. ACh in situ and in vitro relaxed endothelin-1 (ET-1)-contracted control vessels to a smaller magnitude than 5-HT-contracted control vessels. These results suggest, in contrast to previous studies, that endothelium-dependent relaxation is decreased during acute vasospasm following SAH. The decreased endothelium-dependent relaxation is secondary to the underlying ET-1-mediated spasm. The inhibition of endothelium-dependent relaxation observed in situ following SAH cannot be demonstrated in vitro, presumably due to loss of the ET-1-mediated vasospasm.


Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 155
Author(s):  
Ilgiz Gareev ◽  
Ozal Beylerli ◽  
Gjumrakch Aliev ◽  
Valentin Pavlov ◽  
Adel Izmailov ◽  
...  

Intracranial aneurysms (IAs) represent the most complex and relevant problem of modern neurology and neurosurgery. They serve as one of the main causes of non-traumatic subarachnoid hemorrhage (SAH), causing up to 85% of all cases of intracranial hemorrhage, which is associated with frequent disability and high mortality among patients. Unfortunately, the molecular mechanisms of the development and rupture of IAs are still under study. Long non-coding RNAs (lncRNAs) are non-coding RNAs that typically have a length of more than 200 nucleotides. It is known that lncRNAs regulate many processes, such as transcription, translation, cell differentiation, regulation of gene expression, and regulation of the cell cycle. In recent years, a lot of evidence has established their role in human diseases from oncology to cardiovascular disease. Recent studies have shown that lncRNAs may be involved in the pathogenesis of IAs. The study of lncRNAs and its targets in various pathological conditions of a person is a rapidly developing field, and it is likely that the knowledge obtained from these studies regarding the pathogenesis of intracranial aneurysms will have the potential to use lncRNAs in therapy, as well as in the diagnosis and prediction of high aneurysms risk of rupture.


1973 ◽  
Vol 38 (5) ◽  
pp. 591-595 ◽  
Author(s):  
John A. Kusske ◽  
Paul T. Turner ◽  
George A. Ojemann ◽  
A. Basil Harris

✓ The role of ventriculostomy in the treatment of acute hydrocephalus following subarachnoid hemorrhage from intracranial aneurysms is evaluated. Eleven patients treated with an external ventricular drain are compared to a matched control series of untreated patients. Improvement occurred in eight of the 11 treated patients and in only one of the nine patients in the control group. Seven of the patients in the ventriculostomy series improved sufficiently to justify definitive surgery. There were no infections. In 50% of the surviving ventriculostomy patients, permanent shunts were unnecessary. Our data emphasize the deleterious effects of hydrocephalus in the acute period following a subarachnoid hemorrhage and suggest that it may be treated effectively by external ventriculostomy.


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