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New Trends in Molecular Research of Aneurysm and Brain Injury
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New Trends in Molecular Research of Aneurysm and Brain Injury

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 December 2024) | Viewed by 11025

Special Issue Editor

Prof. Dr. Maria Wostrack

E-Mail Website
Guest Editor
Department of Neurosurgery, Medical School of the Technical university of Munich, Munich, Germany
Interests: cerebral aneurysm; subarachnoid hemorrhage; cerebral vasospasm; delayed cerebral ischemia; DCI; brain injury; neuroprotection; delayed ischemic neurological deficit DIND; spine surgery; spinal cord tumor

Special Issue Information

Dear Colleagues, 

A subarachnoid haemorrhage (SAH) caused by a ruptured intracranial aneurysm (IA) is a disastrous brain disease due to its high mortality of 40–50% and high incidence of severe disability among those patients who survive. Although a variety of risk factors have been identified, their respective individual impact on the course of disease and patient outcomes is far from fully investigated. As a common complication of SAH, 30% of patients who survive the initial phase develop delayed ischemic neurological deficits (DINDs) and delayed cerebral ischemia (DCI). Different mechanisms have been proposed, such as parenchymal hypoperfusion due to microvascular constriction and microthrombosis leading to hypoxia within the already compromised tissue or cortical spreading depression, associated with transient or ongoing hypoperfusion and hypoxia.

Similar phenomena of impaired microperfusion have been observed during another devastating condition: traumatic brain injury (TBI), which is one of the leading causes of death or lifelong disability in the 29- to 45-year-old population.

Recently, regarding the relevance of the omics, molecular and genetic factors in cerebrovascular diseases have gained increasing interest. One of the underlying hypotheses is the modulation of inflammation, metabolism, immune responses, and cellular responses which appears to play a crucial role in the formation and rupture of IA, the mechanisms of vascular dysfunction at the microcirculatory level, as well as influencing outcomes including long-lasting neurodegeneration following TBI.

For readers, this Special Issue, “New Trends in Molecular Research of Aneurysm and Brain Injury”, will provide an up-to-date description of the more intriguing aspects of the molecular mechanisms underlying the pathophysiology and outcomes of these diseases.

Prof. Dr. Maria Wostrack
Guest Editor

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Keywords

  • cerebral aneurysm
  • subarachnoid hemorrhage
  • cerebral vasospasm
  • delayed cerebral ischemia (DCI)
  • brain injury
  • traumatic brain injury (TBI)
  • delayed ischemic neurological deficit (DIND)
  • neuroprotection

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Published Papers (5 papers)

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Research

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16 pages, 4416 KiB  
Article
Raloxifene Protects Oxygen-Glucose-Deprived Astrocyte Cells Used to Mimic Hypoxic-Ischemic Brain Injury
by Nicolás Toro-Urrego, Juan P. Luaces, Tamara Kobiec, Lucas Udovin, Sofía Bordet, Matilde Otero-Losada and Francisco Capani
Int. J. Mol. Sci. 2024, 25(22), 12121; https://doi.org/10.3390/ijms252212121 - 12 Nov 2024
Viewed by 2774
Abstract
Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. [...] Read more.
Perinatal asphyxia (PA) is a clinical condition characterized by oxygen supply suspension before, during, or immediately after birth, and it is an important risk factor for neurodevelopmental damage. Its estimated 1/1000 live births incidence in developed countries rises to 5–10-fold in developing countries. Schizophrenia, cerebral palsy, mental retardation, epilepsy, blindness, and others are among the highly disabling chronic pathologies associated with PA. However, so far, there is no effective therapy to neutralize or reduce PA-induced harm. Selective regulators of estrogen activity in tissues and selective estrogen receptor modulators like raloxifene have shown neuroprotective activity in different pathological scenarios. Their effect on PA is yet unknown. The purpose of this paper is to examine whether raloxifene showed neuroprotection in an oxygen–glucose deprivation/reoxygenation astrocyte cell model. To study this issue, T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37 °C in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 h. Cultures were supplemented with raloxifene 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Raloxifene 100 nM and 10 nM improved cell survival—65.34% and 70.56%, respectively, compared with the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene co-treatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-h oxygen–glucose deprivation followed by 3, 6, and 9 h of reoxygenation, respectively. Therefore, raloxifene improved cell survival and mitochondrial membrane potential and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. In this study, raloxifene protected oxygen–glucose-deprived astrocyte cells, used to mimic hypoxic–ischemic brain injury. Two examiners performed the qualitative assessment in a double-blind fashion. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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18 pages, 2795 KiB  
Article
The Haptoglobin Response after Aneurysmal Subarachnoid Haemorrhage
by Soham Bandyopadhyay, Patrick Garland, Ben Gaastra, Ardalan Zolnourian, Diederik Bulters and Ian Galea
Int. J. Mol. Sci. 2023, 24(23), 16922; https://doi.org/10.3390/ijms242316922 - 29 Nov 2023
Cited by 3 | Viewed by 1777
Abstract
Haptoglobin is the body’s first line of defence against the toxicity of extracellular haemoglobin released following a subarachnoid haemorrhage (SAH). We investigated the haptoglobin response after SAH in cerebrospinal fluid (CSF) and serum. Paired CSF and serum samples from 19 controls and 92 [...] Read more.
Haptoglobin is the body’s first line of defence against the toxicity of extracellular haemoglobin released following a subarachnoid haemorrhage (SAH). We investigated the haptoglobin response after SAH in cerebrospinal fluid (CSF) and serum. Paired CSF and serum samples from 19 controls and 92 SAH patients were assayed as follows: ultra-performance liquid chromatography for CSF haemoglobin and haptoglobin, immunoassay for serum haptoglobin and multiplexed CSF cytokines, and colorimetry for albumin. There was marked CSF haptoglobin deficiency: 99% of extracellular haemoglobin was unbound. The quotients for both CSF/serum albumin (qAlb) and haptoglobin (qHp) were used to compute the CSF haptoglobin index (qHp/qAlb). CSF from SAH patients had a significantly lower haptoglobin index compared to controls, especially in Haptoglobin-1 allele carriers. Serum haptoglobin levels increased after SAH and were correlated with CSF cytokine levels. Haptoglobin variables were not associated with long-term clinical outcomes post-SAH. We conclude that: (1) intrathecal haptoglobin consumption occurs after SAH, more so in haptoglobin-1 allele carriers; (2) serum haptoglobin is upregulated after SAH, in keeping with the liver acute phase response to central inflammation; (3) haptoglobin in the CSF is so low that any variation is too small for this to affect long-term outcomes, emphasising the potential for therapeutic haptoglobin supplementation. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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Review

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20 pages, 1092 KiB  
Review
Cerebral Aneurysm: Filling the Gap Between Pathophysiology and Nanocarriers
by Corneliu Toader, Mugurel Petrinel Radoi, Christian-Adelin Covlea, Razvan-Adrian Covache-Busuioc, Milena Monica Ilie, Luca-Andrei Glavan, Antonio-Daniel Corlatescu, Horia-Petre Costin, Maria-Daria Gica and Nicolae Dobrin
Int. J. Mol. Sci. 2024, 25(22), 11874; https://doi.org/10.3390/ijms252211874 - 5 Nov 2024
Viewed by 1673
Abstract
Intracranial aneurysms, characterized by abnormal dilations of cerebral arteries, pose significant health risks due to their potential to rupture, leading to subarachnoid hemorrhage with high mortality and morbidity rates. This paper aim is to explore the innovative application of nanoparticles in treating intracranial [...] Read more.
Intracranial aneurysms, characterized by abnormal dilations of cerebral arteries, pose significant health risks due to their potential to rupture, leading to subarachnoid hemorrhage with high mortality and morbidity rates. This paper aim is to explore the innovative application of nanoparticles in treating intracranial aneurysms, offering a promising avenue for enhancing current therapeutic strategies. We took into consideration the pathophysiology of cerebral aneurysms, focusing on the role of hemodynamic stress, endothelial dysfunction, and inflammation in their development and progression. By comparing cerebral aneurysms with other types, such as aortic aneurysms, we identify pathophysiological similarities and differences that could guide the adaptation of treatment approaches. The review highlights the potential of nanoparticles to improve drug delivery, targeting, and efficacy while minimizing side effects. We discuss various nanocarriers, including liposomes and polymeric nanoparticles, and their roles in overcoming biological barriers and enhancing therapeutic outcomes. Additionally, we discuss the potential of specific compounds, such as Edaravone and Tanshinone IIA, when used in conjunction with nanocarriers, to provide neuroprotective and anti-inflammatory benefits. By extrapolating insights from studies on aortic aneurysms, new research directions and therapeutic strategies for cerebral aneurysms are proposed. This interdisciplinary approach underscores the potential of nanoparticles to positively influence the management of intracranial aneurysms, paving the way for personalized treatment options that could significantly improve patient outcomes. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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13 pages, 2039 KiB  
Review
A Systematic Review and Meta-Analysis of the Pathology Underlying Aneurysm Enhancement on Vessel Wall Imaging
by Ronneil Digpal, Kenton P. Arkill, Regan Doherty, Joseph Yates, Lorna K. Milne, Nicole Broomes, Orestis L. Katsamenis, Jason Macdonald, Adam Ditchfield, Ana Paula Narata, Angela Darekar, Roxana O. Carare, Mark Fabian, Ian Galea and Diederik Bulters
Int. J. Mol. Sci. 2024, 25(5), 2700; https://doi.org/10.3390/ijms25052700 - 26 Feb 2024
Viewed by 1916
Abstract
Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement [...] Read more.
Intracranial aneurysms are common, but only a minority rupture and cause subarachnoid haemorrhage, presenting a dilemma regarding which to treat. Vessel wall imaging (VWI) is a contrast-enhanced magnetic resonance imaging (MRI) technique used to identify unstable aneurysms. The pathological basis of MR enhancement of aneurysms is the subject of debate. This review synthesises the literature to determine the pathological basis of VWI enhancement. PubMed and Embase searches were performed for studies reporting VWI of intracranial aneurysms and their correlated histological analysis. The risk of bias was assessed. Calculations of interdependence, univariate and multivariate analysis were performed. Of 228 publications identified, 7 met the eligibility criteria. Individual aneurysm data were extracted for 72 out of a total of 81 aneurysms. Univariate analysis showed macrophage markers (CD68 and MPO, p = 0.001 and p = 0.002), endothelial cell markers (CD34 and CD31, p = 0.007 and p = 0.003), glycans (Alcian blue, p = 0.003) and wall thickness (p = 0.030) were positively associated with enhancement. Aneurysm enhancement therefore appears to be associated with inflammatory infiltrate and neovascularisation. However, all these markers are correlated with each other, and the literature is limited in terms of the numbers of aneurysms analysed and the parameters considered. The data are therefore insufficient to determine if these associations are independent of each other or of aneurysm size, wall thickness and rupture status. Thus, the cause of aneurysm-wall enhancement currently remains unknown. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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14 pages, 530 KiB  
Review
The Role of Gut and Oral Microbiota in the Formation and Rupture of Intracranial Aneurysms: A Literature Review
by Ann-Kathrin Joerger, Carolin Albrecht, Veit Rothhammer, Klaus Neuhaus, Arthur Wagner, Bernhard Meyer and Maria Wostrack
Int. J. Mol. Sci. 2024, 25(1), 48; https://doi.org/10.3390/ijms25010048 - 19 Dec 2023
Cited by 2 | Viewed by 1992
Abstract
In recent years, there has been a growing interest in the role of the microbiome in cardiovascular and cerebrovascular diseases. Emerging research highlights the potential role of the microbiome in intracranial aneurysm (IA) formation and rupture, particularly in relation to inflammation. In this [...] Read more.
In recent years, there has been a growing interest in the role of the microbiome in cardiovascular and cerebrovascular diseases. Emerging research highlights the potential role of the microbiome in intracranial aneurysm (IA) formation and rupture, particularly in relation to inflammation. In this review, we aim to explore the existing literature regarding the influence of the gut and oral microbiome on IA formation and rupture. In the first section, we provide background information, elucidating the connection between inflammation and aneurysm formation and presenting potential mechanisms of gut–brain interaction. Additionally, we explain the methods for microbiome analysis. The second section reviews existing studies that investigate the relationship between the gut and oral microbiome and IAs. We conclude with a prospective overview, highlighting the extent to which the microbiome is already therapeutically utilized in other fields. Furthermore, we address the challenges associated with the context of IAs that still need to be overcome. Full article
(This article belongs to the Special Issue New Trends in Molecular Research of Aneurysm and Brain Injury)
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