Publicaciones

Non-invasive brain stimulation for functional recovery in animal models of stroke: A systematic review

Rodríguez A, Amaya-Pascasio L, Gutiérrez-Fernández M et al. Neurosci Biobehav Rev. 2024 Jan;156:105485. doi: 10.1016/j.neubiorev.2023.105485. Epub 2023 Nov 30. PMID: 38042359 Review.

https://www.sciencedirect.com/science/article/pii/S0149763423004542?via%3Dihub

Abstract: Motor and cognitive dysfunction occur frequently after stroke, severely affecting a patient´s quality of life. Recently, non-invasive brain stimulation (NIBS) has emerged as a promising treatment option for improving stroke recovery. In this context, animal models are needed to improve the therapeutic use of NIBS after stroke. A systematic review was conducted based on the PRISMA statement. Data from 26 studies comprising rodent models of ischemic stroke treated with different NIBS techniques were included. The SYRCLE tool was used to assess study bias. The results suggest that both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) improved overall neurological, motor, and cognitive functions and reduced infarct size both in the short- and long-term. For tDCS, it was observed that either ipsilesional inhibition or contralesional stimulation consistently led to functional recovery. Additionally, the application of early tDCS appeared to be more effective than late stimulation, and tDCS may be slightly superior to rTMS. The optimal stimulation protocol and the ideal time window for intervention remain unresolved. Future directions are discussed for improving study quality and increasing their translational potential.

Funding: This work was funded by two grants awarded by the Consejería de Salud de la Junta de Andalucía (Ministry of Health of the Andalusian Regional Government), RH-0054-2021 (Torrecardenas University Hospital and University of Almería) and CSyF 2021-Postdoctorales (RPS 24665). Furthermore, this study is part of the Spanish Health Outcomes Oriented Cooperative Research Networks (RICORS-ICTUS), Instituto de Salud Carlos III (Carlos III Health Institute), Ministerio de Ciencia e Innovacion ´ (Ministry of Science and Innovation), RD21/0006/0010 (Torrecardenas University Hospital), RD21/0006/0012 (Hospital La Paz Institute for Health Research).

Synthesis, antioxidant and neuroprotective analysis of diversely functionalized α-aryl-N-alkyl nitrones as potential agents for ischemic stroke therapy

Escobar-Peso A, Martínez-Alonso E et al.  Eur J Med Chem. 2024 Feb 15;266:116133. doi: 10.1016/j.ejmech.2024.116133. Epub 2024 Jan 9. PMID: 38218126

https://pubmed.ncbi.nlm.nih.gov/38218126/

Abstract: Herein, we report the synthesis, antioxidant and biological evaluation of 32 monosubstituted α-arylnitrones derived from α-phenyl-tert-butyl nitrone (PBN) in the search for neuroprotective compounds for ischemic stroke therapy, trying to elucidate the structural patterns responsible for their neuroprotective activity. Not surprisingly, the N-tert-butyl moiety plays beneficious role in comparison to other differently N-substituted nitrone groups. It seems that electron donor substituents at the ortho position and electron withdrawing substituents at the meta position of the aryl ring induce good neuroprotective activity. As a result, (Z)-N-tert-butyl-1-(2- hydroxyphenyl)methanimine oxide (21a) and (Z)-N-tert-butyl-1-(2-(prop-2-yn-1-yloxy)phenyl)methanimine oxide (24a) showed a significant increase in neuronal viability in an experimental ischemia model in primary neuronal cultures, and induced neuroprotection and improved neurodeficit score in an in vivo model of transient cerebral ischemia. These results showed that nitrones 21a and 24a are new effective small and readily available antioxidants, and suitable candidates for further structure optimization in the search for new phenyl-derived nitrones for the treatment of ischemic stroke and related diseases. 

Funding: A.A. and J.M.-C thank the Community of Madrid for support. This work is part of the MINA-CM program (number S2022/BMD-7236), funded by the call for the implementation of programs of R&D activities between research groups of the Community of Madrid in Biomedicine 2022 (Order 1171/2022). This work has been also co-funded by Instituto de Salud Carlos III through the projects PI22/01381 and RD21/0006/0019 and European Union granted to A.A, and the contract IFI18/ 00011 to A.E.-P. 

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial)

Zapata-Arriaza E, Medina-Rodríguez M, Moniche Álvarez F et al. Trials. 2024 Jan 9;25(1):35. doi: 10.1186/s13063-023-07817-9. PMID: 38195586

https://pubmed.ncbi.nlm.nih.gov/38195586/

Abstract:
Rationale In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reoc‑ clusion is yet to be elucidated. Aims To assess efcacy and safety of intravenous tirofban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Sample size estimates Two hundred forty patients will be enrolled, 120 in every treatment arm.
Methods and design A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulflling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofban at a 500-mcg bolus followed by a 200-mcg/h infusion during the frst 24 h. All patients will be followed for up to 3 months

Study outcomes Primary efcacy outcome will be the proportion of patients with carotid in-stent thrombosis within the frst 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage.
Discussion This will be the frst clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL.

Funding: This project was funded by the Instituto de Salud Carlos III (ISCIII) throughvthe project PI21/01322 and co-funded by the European Union. The SpanishvClinical Research Network (SCReNCode: 21.033) also contributed to the study.vThe ITRIBiS project (Improving Translational Research Potential at the Institutevof Biomedicine of Seville) has the registration number REGPOT-2013-1. M.vMedina-Rodríguez was granted a Rio Hortega contract (CM21/00096). Thevproject was included in the Cooperative Cerebrovascular Disease Research Network (INVICTUS) (RD16/0019/0015).