Kynurenic acid (KYNA), a metabolite of tryptophan, as an excitatory amino acid receptor antagonist is an effective neuroprotective agent in case of excitotoxicity, which is the hallmark of brain ischemia and several neurodegenerative processes. Therefore, kynurenine pathway, KYNA itself, and its derivatives came into the focus of research. During the past fifteen years, our research group has developed several neuroactive KYNA derivatives, some of which proved to be neuroprotective in preclinical studies. In this study, the synthesis of these KYNA derivatives and their evaluation with divergent molecular characteristics are presented together with their most typical effects on the monosynaptic transmission in CA1 region of the hippocampus of the rat. Their effects on the basic neuronal activity (on the field excitatory postsynaptic potentials: fEPSP) were studied in in vitro hippocampal slices in 1 and 200 μM concentrations. KYNA and its derivative 4 in both 1 and 200 μM concentrations proved to be inhibitory, while derivative 8 only in 200 μM decreased the amplitudes of fEPSPs. Derivative 5 facilitated the fEPSPs in 200 μM concentration. This is the first comparative study which evaluates the structural and functional differences of formerly and newly developed KYNA analogs. Considerations on possible relations between molecular structures and their physiological effects are presented.

Background: Selecting stroke patients with large vessel occlusion (LVO) based on prehospital stroke scales could provide a faster triage and transportation to a comprehensive stroke centre resulting a favourable outcome. We aimed here to explore the detailed severity assessment of Cincinnati Prehospital Stroke Scale (CPSS) to improve its ability to detect LVO in acute ischemic stroke (AIS) patients. Methods: A cross-sectional analysis was performed in a prospectively collected registry of consecutive patients with first ever AIS admitted within 6 h after symptom onset. On admission stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and the presence of LVO was confirmed by computed tomography angiography (CTA) as an endpoint. A detailed version of CPSS (d-CPSS) was designed based on the severity assessment of CPSS items derived from NIHSS. The ability of this scale to confirm an LVO was compared to CPSS and NIHSS respectively. Results: Using a ROC analysis, the AUC value of d-CPSS was significantly higher compared to the AUC value of CPSS itself (0.788 vs. 0.633, p < 0.001) and very similar to the AUC of NIHSS (0.795, p = 0.510). An optimal cut-off score was found as d-CPSS≥5 to discriminate the presence of LVO (sensitivity: 69.9%, specificity: 75.2%). Conclusion: A detailed severity assessment of CPSS items (upper extremity weakness, facial palsy and speech disturbance) could significantly increase the ability of CPSS to discriminate the presence of LVO in AIS patients.

Thrombolysis (IVT) is effective in the treatment of lacunar stroke (LAC). However, most studies compared the outcome of LAC to a heterogenous control group. We aimed to compare early neurological improvement (ENI) and late functional outcomes following thrombolysis for LAC with a homogenous control group of cardioembolic stroke (CE) without large-vessel occlusion (LVO). Patient data were obtained from the national multicentre STAY ALIVE Acute Stroke Registry. At each centre, a team of vascular neurologists determined the TOAST classification. ENI was defined as a minimum 4-point decrease in the NIHSS score between admission and discharge, or a complete resolution of symptoms. For late functional outcome, we analysed the dichotomised 90-day mRS scores (good outcome was mRS≤2). 142 LAC and 156 CE patients were analysed. Following IVT, the percentage of ENI did not differ significantly (LAC 41.1% vs CE 49.7%, p=0.154), and multivariable analysis did not identify any clinical parameters that would predict ENI after IVT in either group. LAC patients had unfavourable, albeit non-significant, odds of having good 90-day functional outcomes compared to CE patients (aOR 0.483, 95% CI 0.201-1.161, p=104). We report the first analysis of short- and long-term outcomes of IVT in LAC, using a homogenous control group of CE patients without LVO. The prevalence of ENI and 90-day functional outcomes were similar. However, LAC patients had unfavourable odds of achieving good functional outcomes compared to the control group. Therefore, we emphasise that LAC should not be considered a minor stroke subtype.