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An association between Tako-Tsubo cardiomyopathy (TTC) and underlying malignancies has been observed, suggesting that TTC might be the consequence of paraneoplastic phenomena. This study investigates the presence of autoantibodies against cardiomyocytes as well as adrenergic (β 1 , β 2) and muscarinic (M2) receptors in patients with TTC. Serum from 20 TTC patients and 20 controls with ischemic heart disease was obtained. Indirect immunofluorescence testing for intracellular autoantibodies against cardiomyocytes showed a homogenous distribution, as in both groups 9 of 20 sera displayed a characteristic binding pattern of antibodies including vascular walls and intracellular structures. Flow cytometry analysis revealed no difference between TTC and controls in the binding of autoantibodies to the surface antigens of cardiomyocyte HL-1 cells (p = 0.569, t-test). Flow cytometry analysis of nontransfected wild type cells (p = 0.633, t-test), M2 receptor-transfected cells (p = 0.687, t -test), β 1 receptor-transfected cells (p = 0.444, t -test) and β 2 receptor-transfected cells (p = 0.632, t -test) showed similar results for control and TTC sera. Likewise, the binding pattern of TTC patients with a history of neoplasia compared to those without or to controls did not differ significantly (p > 0.05, u-test). Findings suggest that the presumed paraneoplastic etiology of TTC cannot be attributed to the formation of these antibodies. [ABSTRACT FROM AUTHOR]

Objectives Postoperative cognitive decline (POCD) has a perceivable influence on daily living and is noticed more often by close relatives than by patients themselves 3 months after aortic valve replacement. This study aimed to elucidate the longitudinal course of the subjective awareness of POCD. Design Follow-up of a prospective observational study. Setting A single cardiothoracic center in Germany. Participants The study included 108 patients scheduled for elective aortic valve replacement surgery and 85 close relatives of the patients. Interventions In addition to conducting a neuropsychologic examination, the authors previously interviewed 82 patients with a Cognitive Failure Questionnaire for self-assessment (s-CFQ), and 62 relatives with the Cognitive Failure Questionnaire for others (f-CFQ) before and 3 months after surgery. Up until 12 months after surgery, the authors continuously interviewed additional patients (baseline and 3 months after surgery), thereby enlarging the original sample, and included the entire group (108 patients, 85 relatives) for the 12-month follow-up. Results The analysis showed that relatives (p = 0.026) and patients experienced patients’ cognitive decline 3 months after surgery (p = 0.009). All changes still were observed in questions related to memory and attention. After 1 year, the s-CFQ no longer differed between baseline and postoperative assessment. Mean scores in the f-CFQ still were above baseline, barely missing statistical significance (p = 0.051). In patients with “change to worse” in the f-CFQ at 1-year follow-up, declining cognitive results in nonverbal learning (p = 0.021) could be observed 3 months postoperatively. Only a decrease in 3-month f-CFQ correlated with a decline in specific neuropsychologic tests 3 months after surgery. Conclusions Contrary to the authors’ previous results, the impact of POCD on daily living functions also was recognized by the patients themselves. The long-term influence and the associations between subjective deficits and psychometric cognitive measures seemed to be assessed more reliably by close relatives. [ABSTRACT FROM AUTHOR]

Highlights: [•] We aimed to quantify impaired cerebral perfusion in the rat with fpVCT. [•] Imaging of hemodynamic failure in rodents with fpVCT is feasible. [•] FpVCT detects cerebral hypoperfusion even 24h after vessel occlusion. [•] FpVCT can distinguish between consequences of temporary and permanent MCAO. [Copyright &y& Elsevier]

Introduction: Successful thrombectomy improves morbidity and mortality after stroke. The present prospective, observational cohort study investigated a potential correlation between the successful restoration of tissue perfusion by mechanical thrombectomy and intact cerebrovascular autoregulation (CA).Objective: Status of CA in patients with large vessel occlusive stroke after thrombectomy.Methods: After thrombectomy CA was measured using transcranial Doppler ultrasound. For this purpose a moving correlation index (Mxa) based on spontaneous arterial blood pressure fluctuations and corresponding cerebral blood flow velocity changes was calculated. CA impairment was defined by Mxa values more than .3.Results: Twenty patients with an acute occlusion of the middle cerebral artery or distal internal carotid artery were included. A successful recanalization of the occluded vessel via interventional thrombectomy was achieved in 10 of these patients (successful recanalization group), while in 10 patients mechanical recanalization failed or could not be applied (no recanalization group). Mean Mxa at stroke side was .58 ± .21 Table 2a in patients with successful intervention. At the unaffected hemisphere Mxa was .50 ± .20 Table 2a in successful recanalization group and .45 ± .24 Table 2b in no recanalization group without statistically significant differences. Based on the previously defined Mxa cut off more than .3, CA impairment was observable in all successful recanalized patients and in 8 of 10 patients with unsuccessful interventional treatment.Conclusions: These results suggest that brain perfusion may be affected due to impaired CA even after successful mechanical thrombectomy. Therefore, a tight blood pressure management is of great importance in post-thrombectomy stroke treatment to avoid cerebral hypo- and hyperperfusion. [ABSTRACT FROM AUTHOR]

Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor protein predominantly expressed in microglia within the central nervous system (CNS). TREM2 regulates multiple microglial functions, including lipid metabolism, immune reaction, inflammation, and microglial phagocytosis. Recent studies have found that TREM2 is highly expressed in activated microglia after ischemic stroke. However, the role of TREM2 in the pathologic response after stroke remains unclear. Herein, TREM2-deficient microglia exhibit an impaired phagocytosis rate and cholesteryl ester (CE) accumulation, leading to lipid droplet formation and upregulation of Perilipin-2 (PLIN2) expression after hypoxia. Knockdown of TREM2 results in increased lipid synthesis (PLIN2, SOAT1) and decreased cholesterol clearance and lipid hydrolysis (LIPA, ApoE, ABCA1, NECH1, and NPC2), further impacting microglial phenotypes. In these lipid droplet-rich microglia, the TGF-β1/Smad2/3 signaling pathway is downregulated, driving microglia towards a pro-inflammatory phenotype. Meanwhile, in a neuron-microglia co-culture system under hypoxic conditions, we found that microglia lost their protective effect against neuronal injury and apoptosis when TREM2 was knocked down. Under in vivo conditions, TREM2 knockdown mice express lower TGF-β1 expression levels and a lower number of anti-inflammatory M2 phenotype microglia, resulting in increased cerebral infarct size, exacerbated neuronal apoptosis, and aggravated neuronal impairment. Our work suggests that TREM2 attenuates stroke-induced neuroinflammation by modulating the TGF-β1/Smad2/3 signaling pathway. TREM2 may play a direct role in the regulation of inflammation and also exert an influence on the post-ischemic inflammation and the stroke pathology progression via regulation of lipid metabolism processes. Thus, underscoring the therapeutic potential of TREM2 agonists in ischemic stroke and making TREM2 an attractive new clinical target for the treatment of ischemic stroke and other inflammation-related diseases. [Display omitted] • TREM2 regulates multiple microglial functions including lipid metabolism, inflammation, and microglial phagocytosis. • TREM2-deficient microglia exhibit an impaired phagocytosis rate and lipid droplet accumulation. • TREM2 knockdown leads lower TGF-β1 levels and less anti-inflammatory M2 phenotype microglia. • TREM2-deficient microglia display a lower neuroprotective potential. • TREM2 regulates post-ischemic inflammation in both a direct and an indirect way by modulating lipid metabolism. [ABSTRACT FROM AUTHOR]

Highlights • Computer-assisted planimetry is widely used in experimental stroke research. • An acceptable reliability can be achieved after sufficient training of the rater. • Still, even an experienced rater can generate data with serious variation. • Although automated approaches exist, planimetry skills are important in stroke research. • Inter- and intra-rater dependent bias must be considered during study design. Abstract Background Computer-assisted planimetry is widely used in experimental stroke research to assess the size of the ischemic lesion or hemispheric volume. New method Only insufficient data exist on the training required to achieve sufficient reliability in planimetry. Therefore, planimetry was performed over 15 months by two blinded raters who were initially inexperienced in the method. For inter-rater reliability, the hemispheric and lesional volume of 227 male Wistar Unilever rats subjected to middle cerebral artery occlusion were determined in diffusion- and T2-weighted sequences. For the intra-rater agreement, one investigator assessed the hemispheric and lesional volume in 87 T2-weighted sequences twice within a six-week interval. The correlation was calculated using Krippendorff's alpha and Bland-Altman plots illustrated the agreement. Results Inter-rater agreement increased during the first seven weeks and remained at high values (Krippendorff's alpha > 0.88). For intra-rater agreement, Krippendorff's alpha was 0.84 for hemispheric and 0.85 for lesional volume. The Bland-Altman plot indicated solid agreement between raters in the absence of systematic errors. Comparison with existing methods Simplified geometrical models or automated methods for planimetry can be used to determine lesional volume, but both approaches are inappropriate to assess hemispheric volume. Conclusion Computer-assisted planimetry can be an appropriate method to determine hemispheric or ischemic lesion volume in rodents but requires a sufficiently long learning period of approximately two months. Even an experienced investigator can generate data with serious variation. Inter- and intra-rater-dependent bias should be considered during the design and performance of respective studies. [ABSTRACT FROM AUTHOR]