Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.
PPARs (peroxisome-proliferator-activated receptors) are ligand-activated transcriptional factor receptors belonging to the so-called nuclear receptor family. The three isoforms of PPAR (alpha, beta/delta and gamma) are involved in regulation of lipid or glucose metabolism. Beyond metabolic effects, PPARalpha and PPARgamma activation also induces anti-inflammatory and antioxidant effects in different organs. These pleiotropic effects explain why PPARalpha or PPARgamma activation has been tested as a neuroprotective agent in cerebral ischaemia. Fibrates and other non-fibrate PPARalpha activators as well as thiazolidinediones and other non-thiazolidinedione PPARgamma agonists have been demonstrated to induce both preventive and acute neuroprotection. This neuroprotective effect involves both cerebral and vascular mechanisms. PPAR activation induces a decrease in neuronal death by prevention of oxidative or inflammatory mechanisms implicated in cerebral injury. PPARalpha activation induces also a vascular protection as demonstrated by prevention of post-ischaemic endothelial dysfunction. These vascular effects result from a decrease in oxidative stress and prevention of adhesion proteins, such as vascular cell adhesion molecule 1 or intercellular cell-adhesion molecule 1. Moreover, PPAR activation might be able to induce neurorepair and endothelium regeneration. Beyond neuroprotection in cerebral ischaemia, PPARs are also pertinent pharmacological targets to induce neuroprotection in chronic neurodegenerative diseases.
Background: Post-stroke cognitive impairment (PSCI) occurs in approximately half of ischemic stroke survivors. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations is lacking. In this large-scale multicenter lesion-symptom mapping study, we aimed to identify infarct locations most strongly predictive of PSCI, and use this information to develop a prediction model. Methods:We harmonized individual patient data from twelve cohorts through the Meta-VCI-Map consortium. Patients with acute symptomatic infarcts on CT/MRI and cognitive assessment <1 year poststroke were eligible. PSCI was defined as impairment in ≥1 cognitive domains on neuropsychological assessment or impairment on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios for PSCI. For the prediction model, a "location impact score" on a five-point scale was derived from the VLSM results. Combined internal-external validation was performed using leave-one-cohort-out cross-validation for all twelve cohorts. Findings:In our combined sample of 2950 patients (age 67±12 years, 39% female), 44% had PSCI. We achieved almost complete lesion coverage of the brain in our analyses (87%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (False Discovery Rate corrected q<0•01; voxel-wise odds ratios >20). These strategic regions were mapped onto a three-dimensional brain template to visualize PSCI risk per brain region. The location impact score showed good correspondence between predicted and observed risk across cohorts after adjusting for cohortspecific PSCI occurrence. Interpretation:This study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI. A location impact score was derived from this map that robustly predicted PSCI across cohorts and can be applied by clinicians to identify individual patients at risk of PSCI.
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