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Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n= 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterized post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and ΔFosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.

<p>Worldwide, more than 2 million patients die within 30 days after noncardiac surgery anually. Postoperative ischemic myocardial injury is frequent, however, no consensus exists about its definition.</p> <p><strong>Objective: </strong>to develop a term Myocardial Injury after Noncardiac Surgery (MINS) caused by myocardial ischemia, requiring at least, troponin T (TnT) elevation, and with prognostic relevance at 30 days after surgery.</p> <p><strong>Methods: </strong>we performed a prospective study including 15,167 patients ³45 years-old undergoing noncardiac surgery, who had fourth-generation TnT measurements during the first 3 postoperative days. We undertook Cox regression analyses with 30-day mortality after surgery as the dependent variable, using different TnT thresholds, clinical features and several perioperative variables. Non-ischemic etiologies were excluded. Furthermore, we developed a scoring system to predict risk in MINS patients.</p> <p><strong>Results:</strong> MINS was defined as TnT ≥0.03 ng/mL with or without clinical features, and it was an independent predictor of 30-day mortality (adjusted HR 3.82, CI 95% 2.84-5.10). We determined that MINS incidence was 8%, its population attributable risk 33.7%, and 30-days mortality rate 9.6%. Patients did not experience ischemic symptoms in 84% of MINS cases. Additionally, we developed a scoring system in patients suffering MINS with 3 independent predictors of death (age ≥75 years, new ST elevation or left bundle branch block, and anterior location of ECG changes),</p> <p><strong>Conclusion: </strong>Among patients undergoing noncardiac surgery, we defined MINS based on a TnT threshold ≥0.03 ng/mL. Mostly, MINS patients were asymptomatic. Therefore, this strongly suggests the importance of a troponin monitoring during the first few days after surgery.</p> / Master of Health Sciences (MSc)

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25189号 / 医博第5075号 / 新制||医||1072(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 平井 豊博, 教授 江木 盛時, 教授 後藤 慎平 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25500号 / 医博第5100号 / 新制||医||1074(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 齊藤 博英, 教授 松田 秀一, 教授 岩田 想 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM