Jose Carlos Rodrigues Jr¹*, Vithor Ely Bortolin da Silva¹ and Eberval Gadelha Figueiredo²

¹Division of Neurosurgery, Heliópolis Hospital, São Paulo, Brazil
²Divison of Neurosurgery - Clinics Hospital University of Sao Paulo, São Paulo, Brazil

*Corresponding Author: Jose Carlos Rodrigues Jr, Division of Neurosurgery, Heliópolis Hospital, São Paulo, Brazil.

Received: March 07, 2024; Published: June 14, 2024

Abstract

Background: Intracranial aneurysms are a typical lesion ranging from 1% to 5% and causing frequently subarachnoid hemorrhage with high rates of morbidity and mortality. With this devastating scenario, efforts must be directed to improve diagnosis and treatment. Molecular biology of intracranial aneurysms advanced a lot in the last years, improving the understand of their etiology, natural history, and especially, potential targets to be explored in prevention and treatment. In this study, we briefly review the molecular biology of intracranial aneurysms and their potential clinical implications.

Review: In the field of genetics, studies have identified some specific loci in susceptible genes correlate with cell cycle and endothelial function leading to formation of IA. Among them, the gene that appears to be more correlated with formation of IAs, is the elastin gene, located on chromosome 7q11. Others include chromosomes 8q and 9p, associated with a higher risk of IA in cigarette smoking patients. Familial genetic studies reveal that multiple genes must be considered to the etiology of IA. Inflammation seems to be related to the pathogenesis of IA. Several mediators of inflammation (leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators) have been analyzed as contributors to the genesis of IA, and new data suggests that therapies targeting to inhibiting inflammatory cascades could have efficacy in the IA treatment. Metalloproteinases, beyond being candidates as biomarkers for IAs, are also promising therapeutic targets. Imidapril, an ACE (angiotensin-converting enzyme) that acts as a potent inhibitor of matrix metalloproteinase-9 (MMP-9) significantly decreases the size and medial thinning of induced IA. Finally, circulating neutrophils have RNA expression that carries an IA signature promoting potential use to identify patients with IAs, highlighting the possibility to use peripheral blood samples as predictive biomarkers to diagnose IAs before its rupture.

Conclusion: Ruptured IAs remains a catastrophic disease. Efforts to prevention, diagnosis, and treatment must orient our clinical practice. With the recent advances in the field of molecular biology, there is an expectation on the development of target-directed therapy for intracranial aneurysms. Besides, diagnostic and preventive measures using potential biomarkers and genetic screenings may change the natural history of IAs.

 Keywords: Intracranial Aneurysm; Subarachnoid Hemorrhage; Gene; Molecular Biology

References

1. Kassam A., et al. “Altered Arterial Homeostasis and Cerebral Aneurysms: A Review of the Literature and Justification for a Search of Molecular Biomarkers”. Neurosurgery5 (2004): 1199-1212.
2. Chalouhi N., et al. “Biology of intracranial aneurysms: Role of inflammation”. The Journal of Cerebral Blood Flow and Metabolism 9 (2012): 1659-1676.
3. Yokoi T., et al. “Cerebral aneurysms and inflammation”. Neuroimmunology and Neuroinflammation 2 (2015): 55.
4. Zhang J and Claterbuck RE. “Molecular genetics of human intracranial aneurysms”. International Journal of Stroke4 (2008): 272-287.
5. Hemorrhage S., et al. “Hormonal Factors and Risk of Aneurysmal”. Stroke (2001): 606-612.
6. Krischek B and Inoue I. “The genetics of intracranial aneurysms”. Journal of Human Genetics7 (2006): 587-594.
7. Ozturk AK., et al. “Molecular genetic analysis of two large kindreds with intracranial aneurysms demonstrates linkage to 11q24-25 and 14q23-31”. Stroke 4 (2006): 1021-1027.
8. Mohan D., et al. “Genetic factors involves in intracranial aneurysms-actualities”. Journal of Medicine and Life 3 (2015): 336-341.
9. Wang W., et al. “Aberrant expression of lncRNAs and mRNAs in patients with intracranial aneurysm”. Oncotarget 2 (2017): 2477-2484.
10. Ruigrok YM., et al. “Evidence in favor of the contribution of genes involved in the maintenance of the extracellular matrix of the arterial wall to the development of intracranial aneurysms”. Human Molecular Genetics 22 (2006): 3361-3368.
11. Chen L., et al. “Screening of key genes of unruptured intracranial aneurysms by using DNA microarray data analysis techniques”. Genetics and Molecular Research 1 (2014): 758-767.
12. Li Z., et al. “Construction of transcriptional regulatory network in the intracranial aneurysms”. Journal of Clinical and Experimental Medicine1 (2017): 1583-1591.
13. Nakaoka H., et al. “Gene expression profiling reveals distinct molecular signatures associated with the rupture of intracranial aneurysm”. Stroke 8 (2014): 2239-2245.
14. Ishibashi R., et al. “Imidapril Inhibits Cerebral Aneurysm Formation in an Angiotensin-Converting Enzyme-Independent and Matrix Metalloproteinase-9-Dependent Manner”. Neurosurgery 3 (2012): 722-730.
15. Tutino VM., et al. “Circulating neutrophil transcriptome may reveal intracranial aneurysm signature”. PLoS One1 (2018): 1-22.
16. Kataoka H. “Molecular Mechanisms of the Formation and Progression of Intracranial Aneurysms”. Neurologia Medico-Chirurgica (Tokyo)3 (2015): 214-229.
17. Schneider UC., et al. “Functional analysis of Pro-inflammatory properties within the cerebrospinal fluid after subarachnoid hemorrhage in vivo and in vitro”. Journal of Neuroinflammation1 (2012): 28.
18. Kao HW., et al. “Cyclophilin A in ruptured intracranial aneurysm: A prognostic biomarker. Med (United States) 39 (2015): e1683.
19. Peña Silva RA., et al. “Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice”. Hypertension2 (2014): 362-368.
20. Kuruppu S., et al. “Angiotensin (1-7) as a therapy to prevent rupture of intracranial aneurysms? Hypertension 64.2 (2014): 222-223.

Citation

Citation: Jose Carlos Rodrigues Jr., et al. “Molecular Biology of Intracranial Aneurysms and their Clinical Implication”. Acta Scientific Neurology 7.7 (2024): 39-44.

Copyright

Copyright: © 2024 Jose Carlos Rodrigues Jr., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.