Publicaciones

Nanoparticles for Thrombolytic Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Preclinical Studies

Prego-Domínguez J, Laso-García F, Palomar-Alonso N et al. Pharmaceutics. 2025 Feb 6;17(2):208. doi: 10.3390/pharmaceutics17020208. PMID: 40006575.

https://pubmed.ncbi.nlm.nih.gov/40006575/

Abstract: Background: Recombinant tissue plasminogen activator (rtPA) remains the standard thrombolytic treatment for ischemic stroke. Different types of nanoparticles have emerged as promising tools to improve the benefits and decrease the drawbacks of this therapy. Among them, cell membrane-derived (CMD) nanomedicines have gained special interest due to their capability to increase the half-life of particles in blood, biocompatibility, and thrombus targeting. In order to update and evaluate the efficacy of these nanosystems, we performed a meta-analysis of the selected in vivo preclinical studies. Methods: Preclinical in vivo studies in ischemic stroke models have been identified through a search in the Pubmed database. We included studies of rtPA-nanoparticles, which assessed infarct volume and/or neurological improvement. Nanosystems were compared with free (nonencapsulated) rtPA treatment. Standardized mean differences were computed and pooled to estimate effect sizes for lesion volumes and neurological scores. Subgroup analyses by the risk of bias, type of nanoparticle, and time of administration were also performed. Results: A total of 18 publications were included in the meta-analysis. This was based on defined search inclusion criteria. Our analysis revealed that rtPA-nanoparticles improved both lesion volume and neurological scores compared with the free rtPA treatment. Moreover, CMD nanomedicines showed better evolution of infarct volume compared to the other nanoparticles. Funnel plots of lesion volume exhibited asymmetry and publication bias. Heterogeneity was generally high, and the funnel plot and Egger test showed some evidence of publication bias that did not achieve statistical significance in the trim-and-fill analysis. Conclusions: rtPA-encapsulating nanosystems were shown to decrease infarct volume and improve neurological scales compared to the standard treatment, and CMD nanomedicines had the greatest beneficial effect.

Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Instituto de Salud Carlos III_ICIII, grant numbers: ICI19/00032, PI20/01014; and the RICORS-ICTUS network: RD21/0006/0003. Xunta de Galicia, grant number: IN607A2022/02. European Union program FEDER, ISCIII Project (AC20/00031), and Euronanomed III Call (Euronanomed2020_143), and Fundación Mutua Madrileña. CC-P would like to thank Sara Borrell (CD23/00005). All authors have read and agreed to the published version of the manuscript.

Relevance of persistent perfusion deficits on clinical outcomes after successful endovascular treatment: a prospective serial magnetic resonance study

Valls Carbó A, Palomar A, Laredo C et al. Front Neurol. 2025 Feb 27;16:1478240. doi: 10.3389/fneur.2025.1478240. eCollection 2025. PMID: 40083459

https://pubmed.ncbi.nlm.nih.gov/40083459/

Background: Half of the patients who undergo successful recanalization after endovascular treatment (EVT) experience poor clinical outcomes. Impaired microvascular reperfusion (IMR) may explain this lack of improvement, but its frequency and clinical significance remain unclear. The study aims to describe the frequency and associated factors of IMR.

Materials and methods: We conducted a study on a cohort of patients with anterior large artery occlusion, treated with EVT at a single center, who achieved mTICI ≥2C. Perfusion MRI was obtained at arrival, up to 2 h after EVT (post-EVT MRI), and on day 5. IMR was observed only on the post-EVT relative cerebral blood volume (rCBV) maps as voxels within the follow-up ischemic lesion, exhibiting a > 15% asymmetry compared to a mirror homolog, in the absence of internal carotid occlusion, hemorrhagic transformation, or arterial reocclusion. Patients with an IMR volume greater than 5 mL were defined as having significant IMR. IMR was analyzed as a binary variable (presence/absence using the 5 mL cut-off) and by total and relative volume.

Results: IMR was present in 8 out of 33 patients (24.2%), with 4 out of 11 (36.4%) having mTICI 2C, and 4 out of 22 (18.2%) having mTICI 3. After adjustment for relevant variables, absolute and relative IMR volumes were associated with higher National Institutes of Health Stroke Scale (NIHSS) scores at 5 days (adjusted beta =0.50 [0.05, 0.96], p = 0.03) and at 24 h (adjusted beta = 0.11 [0.02, 0.19], p = 0.01). No independent associations were found between IMR and the 90-day modified Rankin Scale (mRS). Conclusion: IMR is present in one-quarter of patients and is associated with worse early neurological outcomes.

Funding: The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The study was funded by project “PI21/01548”, Instituto de Salud Carlos III and co-funded by European Union (ERDF, “A way to make Europe” and project “RD21/0006/0024”, Instituto de Salud Carlos III and the Next Generation EU funds that finance the actions of the Recovery and Resilience Mechanism (MRR).