a-murine-model-of-carotid-aneurysm-formation

A Murine Model of Carotid Aneurysm Formation

Cerebral aneurysms are present in approximately 2%-5% of the population and represent a significant public health concern due to their high rates of ...

University of Pittsburgh Medical Center

Columbia Irving Medical Center

Macrophages and neutrophils have been separately implicated in cerebral aneurysm formation. The interactions between different myeloid subsets and the contributions of macrophage phenotypes in these lesions over time are not known. The purpose of the study was to examine macrophage phenotypic changes in cerebral aneurysms.

M1 macrophages are required for murine cerebral aneurysm formation.

Preoperative chronic narcotic use has been linked to poor outcomes after surgery for degenerative spinal disorders in the form of lower health-related quality of life scores, higher revision rates, increased infections, lower likelihood of return to work, and higher 90-day readmission rates. This study evaluated the impact of preoperative chronic narcotic use on patient reported outcome measures following adult spinal reconstructive surgery.

Preoperative Chronic Opiate Use and Patient Reported Outcomes Following Adult Spinal Reconstructive Surgery.

Establishing central venous access is important to provide fluid resuscitation or medications intravenously to patients.

Intraoperative ultrasound evidence of accidental simultaneous cannulation of the common carotid artery and internal jugular vein: illustrative case.

An arachnoid web is a pathological formation of the arachnoid membrane. It is a rare phenomenon but is known to lead to syrinx formation in the spinal cord along with pain and neurological deficits. On imaging, the 'scalpel sign' is pathognomonic for an arachnoid web. The etiology of syrinx formation from an arachnoid web is currently unknown. This report documents the only two cases of arachnoid webs with an extensive syrinx in which a likely pathophysiologic mechanism is identified. Both cases presented with motor deficits. The patients had no history of trauma or infection. After extensive workup in both patients and observation of the scalpel sign an arachnoid web was suspected. In both cases, the patients were treated surgically after an arachnoid web was suspected. Intra-operative ultrasound visualized in both cases demonstrates a fenestration in the web that allowed passage of cerebrospinal fluid in a rostral-caudal direction due to a ball-valve effect.

Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases.

Recent literature suggests that spinal infections are increasing in prevalence. Any compartment can be infected in the spine; however, multicompartmental infections are rare.

Tetra-compartmental spinal infection with conus medullaris syndrome: illustrative case.

Intracranial aneurysms are reported to affect 2-5% of the population. Despite advances in the surgical management of this disease, diagnostic technologies have marginally improved and still rely on expensive or invasive imaging procedures. Currently, there is no blood-based test to detect cerebral aneurysm formation or quantify the risk of rupture. The aim of this review is to summarize current literature on the mechanism of aneurysm formation, specifically studies relating to inflammation, and provide a rationale and commentary on a hypothetical future blood-based test. Efforts should be focused on clinical-translational approaches to create an assay to screen for cerebral aneurysm presence and risk-stratify patients to allow for superior treatment timing and management. Cerebral Aneurysm Blood Test Considerations: There are multiple caveats to development of a putative blood test to detect cerebral aneurysm presence.

A Future Blood Test to Detect Cerebral Aneurysms.

  Stereotactic radiosurgical rhizolysis of the trigeminal nerve is an established modality increasingly employed to alleviate the symptoms of refractory trigeminal neuralgia. This study analyzes the academic impact of the top 100 cited articles on the radiosurgical management of trigeminal neuralgia.   The Scopus database was searched for articles containing "radiosurgery" and one or more of "trigeminal neuralgia," "trigeminus neuralgia," and "tic douloureux." The top 100 articles written in English were arranged in descending order by citation count. Documents were evaluated for authors, publication year, journal and impact factor, total citations, nationality, study type, radiosurgical modality, and the affiliated institution. Quantitative and qualitative analyses were performed on the data.   The most cited articles were published between 1971 and 2019. The average citation per year was 4.3. The most targeted anatomic area was the "root entry zone" or proximal portion of the cisternal segment of the trigeminal nerve. The most utilized modality was Gamma Knife radiosurgery. The country with the highest number of publications was the United States. Thirty-six percent of the articles were published in the  . Lunsford, Kondziolka, Flickinger, and Régis, respectively, were the most frequently listed co-authors. The most prolific institute was the University of Pittsburgh Medical Center.   Stereotactic radiosurgery is an important modality in the management of medically or surgically refractory trigeminal neuralgia. This analysis assesses its contributions over the past five decades to identify trends in treatment practices for neurosurgeons and to highlight areas where further study is needed.

Bibliometric Analysis of the Top 100 Cited Articles on Stereotactic Radiosurgery for Trigeminal Neuralgia.

Maladaptive inflammation underlies the formation and rupture of human intracranial aneurysms. There is a growing body of evidence that anti-inflammatory pharmaceuticals may beneficially modulate this process. Clopidogrel (Plavix) is a commonly used irreversible P2Y12 receptor antagonist with anti-inflammatory activity. In this paper, we investigate whether clopidogrel is associated with the likelihood of aneurysm rupture in a multi-institutional propensity-matched cohort analysis. Patients presenting for endovascular treatment of their unruptured intracranial aneurysms and those presenting with aneurysm rupture between 2015 and 2019 were prospectively identified at two quaternary referral centers. Patient demographics, comorbidities, and medication usage at the time of presentation were collected. Patients taking clopidogrel or not taking clopidogrel were matched in a 1:1 fashion with respect to location, age, smoking status, aneurysm size, aspirin usage, and hypertension. A total of 1048 patients with electively treated aneurysms or subarachnoid hemorrhages were prospectively identified. Nine hundred twenty-one patients were confirmed to harbor aneurysms during catheter-based diagnostic angiography. A total of 172/921 (19%) patients were actively taking clopidogrel at the time of presentation. Three hundred thirty-two patients were matched in a 1:1 fashion. A smaller proportion of patients taking clopidogrel at presentation had ruptured aneurysms than those who were not taking clopidogrel (6.6% vs 23.5%, p < .0001). Estimated treatment effect analysis demonstrated that clopidogrel usage decreased aneurysm rupture risk by 15%. We present, to the best of our knowledge, the first large-scale multi-institutional analysis suggesting clopidogrel use is protective against intracranial aneurysm rupture. It is our hope that these data will guide future investigation, revealing the pathophysiologic underpinning of this association.

Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis.

Gram-negative rod (GNR) bacterial ventriculitis is a rare complication of shunt-dependent hydrocephalus, often requiring an extended and invasive treatment course. Accumulation of purulent material, as well as empyema and septation formation, limits circulation of antibiotics and infection clearance. Supplementation of standard care with neuroendoscopic-guided intraventricular lavage with lactated Ringer solution and fenestration of septations may facilitate infection clearance and simplify the eventual shunt construct required. Here, the utility of serial lavage for ventriculitis is described in a population of shunt-dependent neonates and infants at high risk for morbidity and mortality.

Serial Neuroendoscopic Lavage for the Treatment of Elevated Cerebrospinal Fluid Protein Levels in Infants with Gram-Negative Rod Ventriculitis.

Cerebral vasospasm and the resultant delayed cerebral infarction is a significant source of mortality following aneurysmal SAH. Vasospasm is currently detected using invasive or expensive imaging at regular intervals in patients following SAH, thus posing a risk of complications following the procedure and financial burden on these patients. Currently, there is no blood-based test to detect vasospasm.

Advances in biomarkers for vasospasm - Towards a future blood-based diagnostic test.

Platelet aggregation is intimately associated with vascular inflammation and is commonly seen on routine histology studies of cerebral aneurysms. Platelets, when activated, have been shown to augment neutrophil response and the pro-inflammatory cascade. Platelet-neutrophil complexes have been found to aggravate atherosclerosis through a positive feedback loop. We hypothesized that targeting platelet aggregation and downstream inflammation could be used to prevent aneurysm formation and progression. First, we induced cerebral aneurysm formation in a previously described intracranial aneurysm model via carotid artery ligation, hypertension, and stereotactic elastase injection in C57BL/6 mice and analyzed vessels for lesion and thrombus formation. Raybiotech cytokine arrays were used to analyze 96 cytokines in induced murine aneurysms and 120 cytokines in human tissue samples. Cerebral aneurysm formation and inflammatory pathway were then studied in animals treated with IgG2 antibody (control), anti-GpIb antibody (platelet depletion), 1:10 DMSO:PBS (control), clopidogrel, anti-CXCR1/2 small molecule inhibitor, or anti-CXCL7 antibody. Bleeding assays and flow cytometry were used to evaluate platelet function in treated groups. CD31 + platelet aggregates are a common feature in human and mouse cerebral aneurysm specimens. Platelet ablation in mice prevents cerebral aneurysm formation (20% vs 100% in control antibody-treated mice, n = 5 each, p = 0.0476). Mice treated with 1 mg/kg clopidogrel develop significantly less aneurysms than controls (18% vs 73%, n = 11 and 11, respectively, p = 0.03). Semi-quantitative analysis of 96 different cytokines using Raybiotech arrays shows increased protein expression of CXCL7 in murine cerebral aneurysms when compared to controls. Treatment with clopidogrel results in reciprocal decrease in detected CXCL7. Targeting CXCL7-CXCR1/2 axis with 10 mg/kg reparixin (CXCR1/2 antagonist) significantly decreases cerebral aneurysm formation (11% vs 73%, n = 9 and 11, p = 0.0098) while treatment with 10 mg/kg SB225002 tends to decrease aneurysm formation (36% vs 73%, n = 11 vs n = 7, p = 0.11). Lastly, specific antibody blockade against CXCL7 using anti-CXCL7 antibody at 100 ug/mL significantly decreases cerebral aneurysm formation (29% vs 75%, n = 7 vs n = 8, p = 0.046). Platelet inflammation has an important role in cerebral aneurysm formation. Small molecule inhibitors targeting platelet CXCL7-CXCR1/2 inflammatory axis could be used to prevent cerebral aneurysm formation or progression.

Article	Year
M1 macrophages are required for murine cerebral aneurysm formation. Journal of neurointerventional surgery\| PubMed ID: 28196918	2018
Preoperative Chronic Opiate Use and Patient Reported Outcomes Following Adult Spinal Reconstructive Surgery. World neurosurgery\| PubMed ID: 32698082	2020
Intraoperative ultrasound evidence of accidental simultaneous cannulation of the common carotid artery and internal jugular vein: illustrative case. Journal of neurosurgery. Case lessons\| PubMed ID: 36083774	2022
Arachnoid webs causing rostral syrinx due to ball-valve effect: an illustrative report of two cases. British journal of neurosurgery\| PubMed ID: 36636902	2024
Tetra-compartmental spinal infection with conus medullaris syndrome: illustrative case. Journal of neurosurgery. Case lessons\| PubMed ID: 36748756	2023
A Future Blood Test to Detect Cerebral Aneurysms. Cellular and molecular neurobiology\| PubMed ID: 37046105	2023
Bibliometric Analysis of the Top 100 Cited Articles on Stereotactic Radiosurgery for Trigeminal Neuralgia. Asian journal of neurosurgery\| PubMed ID: 37056872	2023
Clopidogrel Is Associated with Reduced Likelihood of Aneurysmal Subarachnoid Hemorrhage: a Multi-Center Matched Retrospective Analysis. Translational stroke research\| PubMed ID: 37470917	2024
Serial Neuroendoscopic Lavage for the Treatment of Elevated Cerebrospinal Fluid Protein Levels in Infants with Gram-Negative Rod Ventriculitis. Pediatric neurosurgery\| PubMed ID: 37703859	2023
Advances in biomarkers for vasospasm - Towards a future blood-based diagnostic test. World neurosurgery: X\| PubMed ID: 38487683	2024
Blockade of the Platelet-Driven CXCL7-CXCR1/2 Inflammatory Axis Prevents Murine Cerebral Aneurysm Formation and Rupture. Translational stroke research\| PubMed ID: 39499487	2025

Kamil Nowicki

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