High prevalence of non-alcoholic fatty liver disease in patients with a first episode of acute ischemic stroke. Impact on disability and death

Lidia Canillas; Agnes Soriano Varela; Ana Rodríguez-Campello; Eva Giralt-Steinhauer; Elisa Cuadrado-Godia; Teresa Broqueta. Front Endocrinol. 2022 Dec 16;13:1003878.. doi: 10.3389/fendo.2022.1003878. eCollection 2022.

https://pubmed.ncbi.nlm.nih.gov/36589812/

Conclusion: Presence of NAFLD did not impact on disability and death after the stroke. However, patients with a first episode of stroke showed a high prevalence of NAFLD, especially at intermediate ages, and therefore, screening for NAFLD should be advisable.

Funding: Supported in part by “RICORS-ICTUS RD21/0006/0021)”grant, funded by Instituto de Salud Carlos III (ISCIII) and cofunded by the European Union.

Mitochondrial sodium/calcium exchanger NCLX regulates glycolysis in astrocytes, impacting on cognitive performance

Cabral-Costa JV, Vicente-Gutiérrez C, Agulla J, Lapresa R, Elrod JW, Almeida Á, Bolaños JP, Kowaltowski AJ. J Neurochem. 2022 Dec 23. doi: 10.1111/jnc.15745. Online ahead of print. PMID: 36563047
Abstract: Intracellular Ca2+ concentrations are strictly controlled by plasma membrane transporters, the endoplasmic reticulum, and mitochondria, in which Ca2+ uptake is mediated by the mito c ho nd r ia l c a lc ium unip o rte r c o mp le x (M C Uc ), while e fflu x occurs ma in ly through the mito c ho nd r ia l Na+/Ca2+ exchanger (N C LX). RNAseq database repository searches led us to identify the Nclx transcript as highly enriched in astrocytes when compared to neurons. To assess the role of NCLX in mo us e p rima ry c ulture astrocytes, we inhib ited its functio n both pharmacologically or genetically. This re s ulte d in re -shaping of c yto s o lic C a2+ signa ling and a me ta b o lic s hift that increased glycolyt ic flux and lactate secretion in a C a2+-dependent manner. Interestingly, in v iv o genetic deletion of N CLX in hippocampal astrocytes improved cognit ive performance in behavioral tasks, whereas hippocampal neuron-specific deletion of NCLX imp a ire d cognitive performance. These results unveil a role for N CLX as a novel modulator of astrocytic glucose metabolism, impacting on cognition.
Funding: Authors were supported by grant #2020/06970–5 from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Centro de Pesquisa, Inovação e Difusão de Processos Redox em Biomedicina (CEPID Redoxoma, FAPESP grant #2013/07937–8); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) line 001; Agencia Estatal de Investigación (PID2019-105699RB-I00/AEI/10.13039/501100011033, PDC2021-121013-I00 and RED2018‐102576‐T to JPB); Plan Nacional de Drogas (2020I028 to JPB); Instituto de Salud Carlos III (PI21/00727 and RD21/0006/0005 co-funded by the European Union FEDER/FSE+ and NextGenerationEU to AA); and Junta de Castilla y León(CS/151P20 co-funded by P.O. FEDER to AA; Apoyo Regional a la Competitividad Empresarial, ICE 04/18/LE/0017 to JPB, and Escalera de Excelencia CLU-2017-03 to JPB and AA). JVCC was also supported by FAPESP fellowships #2017/14713-0 and #2019/22178-2.

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients

Palà E, Escudero-Martínez I, Penalba A, Bustamante A, Lamana-Vallverdú M et al. J Stroke Cerebrovasc Dis. 2022 Dec;31(12):106833. doi: 10.1016/j.jstrokecerebrovasdis.2022.106833. Epub 2022 Oct 26.PMID: 36309005
Background: Atrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk. Methods: The present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score 1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain
MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany. Results: 45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to
be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.9923.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment. Conclusions: BMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.
Funding: A Junta de Andalucía grant (PIN-0144-2016) supported partially the study. The Fundacion Cajasol contributed to the study. Neurovascular Research Groups at Seville and Barcelona are part of the Spanish Neurovascular Disease Research Network (RICORS-ICTUS, RD21/0006/0007).

Improving the Efficacy of Quinolylnitrones for Ischemic Stroke Therapy, QN4 and QN15 as New Neuroprotective Agents after Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Injury

Alonso JM, Escobar-Peso A, Fernández I, Alcázar A, Marco-Contelles J. Pharmaceuticals (Basel). 2022 Nov 7;15(11):1363. doi: 10.3390/ph15111363.PMID: 36355534
Abstract: In our search for new neuroprotective agents for stroke therapy to improve the pharmacological profile of the compound quinolylnitrone QN23, we have prepared and studied sixteen new, related and easily available quinolylnitrones. As a result, we have identified compounds QN4 and QN15 as promising candidates showing high neuroprotection power in a cellular experimental model of ischemia. Even though they were found to be less active than our current lead compound QN23, QN4 and QN15 provide an improved potency and, particularly for QN4, an expanded range of tolerability and improved solubility compared to the parent compound. A computational DFT-based
analysis has been carried out to understand the antioxidant power of quinolylnitrones QN23, QN4 and QN15. Altogether, these results show that subtle, simple modifications of the quinolylnitrone scaffold are tolerated, providing high neuroprotective activity and optimization of the pharmacological potency required for an improved design and future drug developments in the field.
Funding: This work was supported by Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund (FEDER), grant number PI18/0255 and RETICS RD21/0006/0019, to A.A, and by MINECO (Government of Spain) grant number SAF-2015-65586-R to J.M.-C