Año: 2022

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Morel S, Hostettler IC, Spinner GR, Bourcier R, Pera J et al. J Pers Med. 2022 Aug 30;12(9):1410. doi: 10.3390/jpm12091410. PMID: 36143196
Abstract: Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate
analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making.
Funding: The @neurIST project was supported by the 6th framework program of the European Commission (FP6-IST-2004-027703). Geneva data collection was part of the AneuX project supported by the Swiss SystemsX.ch initiative (PB), evaluated by the Swiss National Science Foundation, and
which also funded the SyBIT project (web applications for data exploration). YMR has received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (PRYSM, grant agreement No. 852173). MKB and YMR were supported by the Netherlands Cardiovascular Research Initiative: An initiative with support of the Dutch Heart Foundation, CVON2015-08 ERASE. DW was supported by NIH Funding. RR was supported by the French Regional Council of Pays-de-la-Loire (VaCaRMe program) and the Agence Nationale de la Recherche (ANR-15-CE17-0008-01 to G.L). HD and RB were supported by the French Ministry of Health (Clinical trial NCT02848495 to HD), the Genavie Foundation, the Société Française de Radiologie and the Société Française de Neuroradiologie. JJC and ECG were supported in part by Spain’s Ministry of Health (Instituto de Salud Carlos III Fondo de Investigaciones sanitarias P19/00011 and by “RICORS-ICTUS RD21/0006/0021). GAR was supported by the Canadian Institutes of Health Research. MN was supported by the Helsinki University Central Hospital EVO grant TYH2018316. The GOSH study was funded by the Stroke Association. Funders were not involved in the study design, in the analysis of the data or in the interpretation of the results.

Postischemic Neuroprotection of Aminoethoxydiphenyl Borate Associates Shortening of Peri-Infarct Depolarizations

Fernández-Serra R, Martínez-Alonso E, Alcázar A, Chioua M, Marco-Contelles J, Martínez-Murillo R, Ramos M, Guinea GV, González-Nieto D. Int J Mol Sci. 2022 Jul 4;23(13):7449. doi: 10.3390/ijms23137449.PMID: 35806455
Abstract: Brain stroke is a highly prevalent pathology and a main cause of disability among older adults. If not promptly treated with recanalization therapies, primary and secondary mechanisms of injury contribute to an increase in the lesion, enhancing neurological deficits. Targeting excitotoxicity and oxidative stress are very promising approaches, but only a few compounds have reached the clinic with relatively good positive outcomes. The exploration of novel targets might overcome the lack of clinical translation of previous efficient preclinical neuroprotective treatments. In this study, we examined the neuroprotective properties of 2-aminoethoxydiphenyl borate (2-APB), a molecule that interferes with intracellular calcium dynamics by the antagonization of several channels and receptors. In a permanent model of cerebral ischemia, we showed that 2-APB reduces the extent of the damage and preserves the functionality of the cortical territory, as evaluated by somatosensory evoked potentials (SSEPs). While in this permanent ischemia model, the neuroprotective effect exerted by the antioxidant scavenger cholesteronitrone F2 was associated with a reduction in reactive oxygen species (ROS) and better neuronal survival in the penumbra, 2-APB did not modify the inflammatory response or decrease the content of ROS and was mostly associated with a shortening of peri-infarct depolarizations, which translated into better cerebral blood perfusion in the penumbra. Our study highlights the potential of 2-APB to target spreading depolarization events and their associated inverse hemodynamic changes, which mainly contribute to extension of the area of lesion in cerebrovascular pathologies.
Funding: This research was funded by the Ministerio de Economía y Competitividad Grants MAT2016-79832-R (to G.V.G. and D.G.-N.) and SAF2015-65586-R (to J.M.-C.), ISCIII and FEDER grant RD21/0006/0019 (to A.A.), Ministerio de Ciencia e Innovación grant PID2020-116403RB-I00 funded by MCIN/AEI/10.13039/501100011033 (to D.G.-N.) and funds from the regional government of Madrid: Neurocentro-B2017/BMD-3760 (to G.V.G., R.M.-M. and D.G.-N.) and IND2018/BMD-9804 (to G.V.G.).