Stress and Corticosteroids Modulate Muscarinic Long Term Potentiation (mLTP) in the Hippocampus

Stress influences synaptic plasticity, learning and memory in a steroid hormone receptor dependent manner. Based on these findings it has been proposed that stress could be a major risk factor for the development of cognitive decline and dementia. Interestingly, evidence has been provided that stress also affects muscarinic, i.e., acetylcholine (ACh)-mediated neurotransmission. To learn more about the impact of stress and steroids on synaptic plasticity, in this study, we investigated the effects of stress on muscarinic long term potentiation (mLTP). We report that multiple, unpredictable exposure to stress depresses carbachol (0.5 μM)-induced mLTP, while this effect of stress is not observed in hippocampal slices prepared from mice exposed only to a single stressful procedure. Furthermore, we demonstrate that activation of distinct steroid hormone receptors is involved in stress-mediated alterations of mLTP. Activation of mineralocorticoid receptors (MR) promotes mLTP, while glucocorticoid receptor (GR) activity impairs mLTP. These effects of multiple unpredictable stress on mLTP are long-lasting since they are detected even two weeks after the last stressful experience. Thus, multiple unpredictable events rather than a single stressful experience affect mLTP in a steroid hormone receptor dependent manner, suggesting that chronic unpredictable stress can lead to lasting alterations in hippocampal cholinergic plasticity

Role of Thrombin in Central Nervous System Injury and Disease

Thrombin is a Na+-activated allosteric serine protease of the chymotrypsin family involved in coagulation, inflammation, cell protection, and apoptosis. Increasingly, the role of thrombin in the brain has been explored. Low concentrations of thrombin are neuroprotective, while high concentrations exert pathological effects. However, greater attention regarding the involvement of thrombin in normal and pathological processes in the central nervous system is warranted. In this review, we explore the mechanisms of thrombin action, localization, and functions in the central nervous system and describe the involvement of thrombin in stroke and intracerebral hemorrhage, neurodegenerative diseases, epilepsy, traumatic brain injury, and primary central nervous system tumors. We aim to comprehensively characterize the role of thrombin in neurological disease and injury

Does Malignancy Status Effect Outcomes in Patients With Large Vessel Occlusion Stroke and Cancer Who Underwent Endovascular Thrombectomy?

Background Cancer is associated with an increased risk of acute ischemic stroke, including large vessel occlusions. Whether cancer status affects outcomes in patients with large vessel occlusions that undergo endovascular thrombectomy remains unknown. Methods and Results All consecutive patients undergoing endovascular thrombectomy for large vessel occlusions were recruited into a prospective ongoing multicenter database, and the data were retrospectively analyzed. Patients with active cancer were compared with patients with cancer in remission. Association of cancer status with 90‐day functional outcome and mortality were calculated in multivariable analyses. We identified 154 patients with cancer and large vessel occlusions that underwent endovascular thrombectomy (mean age, 74±11; 43% men; median National Institutes of Health Stroke Scale 15). Of the included patients, 70 (46%) had a remote history of cancer or cancer in remission, and 84 (54%) had active disease. Outcome data at 90 days poststroke were available for 138 patients (90%) and was classified as favorable in 53 (38%). Patients with active cancer were younger and more often smoked but did not significantly differ from those without malignancy in other risk factors, stroke severity, stroke subtype, or procedural variables. Favorable outcome rates among patients with active cancer did not significantly differ compared with those seen in patients without active cancer, but mortality rates were significantly higher among patients with active cancer on univariate and multivariable analyses. Conclusions Our study suggests that endovascular thrombectomy is safe and efficacious in patients with history of malignancy as well as in those with active cancer at the time of stroke onset, although mortality rates are higher among patients with active cancer

The impact on clinical outcomes after 1 year of implementation of an artificial intelligence solution for the detection of intracranial hemorrhage

Abstract Background To assess the effect of a commercial artificial intelligence (AI) solution implementation in the emergency department on clinical outcomes in a single level 1 trauma center. Methods A retrospective cohort study for two time periods—pre-AI (1.1.2017–1.1.2018) and post-AI (1.1.2019–1.1.2020)—in a level 1 trauma center was performed. The ICH algorithm was applied to 587 consecutive patients with a confirmed diagnosis of ICH on head CT upon admission to the emergency department. Study variables included demographics, patient outcomes, and imaging data. Participants admitted to the emergency department during the same time periods for other acute diagnoses (ischemic stroke (IS) and myocardial infarction (MI)) served as control groups. Primary outcomes were 30- and 120-day all-cause mortality. The secondary outcome was morbidity based on Modified Rankin Scale for Neurologic Disability (mRS) at discharge. Results Five hundred eighty-seven participants (289 pre-AI—age 71 ± 1, 169 men; 298 post-AI—age 69 ± 1, 187 men) with ICH were eligible for the analyzed period. Demographics, comorbidities, Emergency Severity Score, type of ICH, and length of stay were not significantly different between the two time periods. The 30- and 120-day all-cause mortality were significantly reduced in the post-AI group when compared to the pre-AI group (27.7% vs 17.5%; p = 0.004 and 31.8% vs 21.7%; p = 0.017, respectively). Modified Rankin Scale (mRS) at discharge was significantly reduced post-AI implementation (3.2 vs 2.8; p = 0.044). Conclusion The added value of this study emphasizes the introduction of artificial intelligence (AI) computer-aided triage and prioritization software in an emergent care setting that demonstrated a significant reduction in a 30- and 120-day all-cause mortality and morbidity for patients diagnosed with intracranial hemorrhage (ICH). Along with mortality rates, the AI software was associated with a significant reduction in the Modified Ranking Scale (mRs)