Summary The ε4 allele of APOE -encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer’s disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production. Secretory factors in conditioned media from ApoE4 astrocytes significantly increased amyloid precursor protein (APP) levels and Aβ secretion in neurons. We further found that increased cholesterol secretion from ApoE4 astrocytes was necessary and sufficient to induce the formation of lipid rafts that potentially provide a physical platform for APP localization and facilitate its processing. Our study reveals the contribution of ApoE4 astrocytes to amyloidosis in neurons by expanding lipid rafts and facilitating Aβ production through an oversupply of cholesterol.
Background Delayed emergence from general anesthesia is associated with life-threatening conditions with pharmacological, neurological, metabolic, and rarely, psychiatric causes. This case report was presented to report psychogenic coma after recovery from anesthesia with remimazolam and remifentanil. Case An elderly woman was unresponsive after recovery from anesthesia with remimazolam and remifentanil. Physical examination, laboratory testing, and radiographic imaging did not reveal any obvious organic causes. Pharmacological or metabolic abnormalities were not found. Absence of those causes strongly suggests that prolonged unconsciousness is related to psychiatric origin. The patient spontaneously regained consciousness after 48 h without any neurological complications. Conclusions Anesthesiologists should be aware of the possibility of psychogenic coma for patients with unexplained delay in emergence from anesthesia after the exclusion of other causes.
IntroductionLomerizine is a calcium channel blocker that crosses the blood–brain barrier and is used clinically in the treatment of migraines. However, whether lomerizine is beneficial in modulating neuroinflammatory responses has not been tested yet.MethodsTo assess the potential of lomerizine for repurposing as a treatment for neuroinflammation, we investigated the effects of lomerizine on LPS-induced proinflammatory responses in BV2 microglial cells, Alzheimer’s disease (AD) excitatory neurons differentiated from induced pluripotent stem cells (iPSCs), and in LPS-treated wild type mice.ResultsIn BV2 microglial cells, lomerizine pretreatment significantly reduced LPS-evoked proinflammatory cytokine and NLRP3 mRNA levels. Similarly, lomerizine pretreatment significantly suppressed the increases in Iba-1, GFAP, proinflammatory cytokine and NLRP3 expression induced by LPS in wild-type mice. In addition, lomerizine posttreatment significantly decreased LPS-stimulated proinflammatory cytokine and SOD2 mRNA levels in BV2 microglial cells and/or wild-type mice. In LPS-treated wild-type mice and AD excitatory neurons differentiated from iPSCs, lomerizine pretreatment ameliorated tau hyperphosphorylation. Finally, lomerizine abolished the LPS-mediated activation of GSK3α/β and upregulation of DYRK1A, which is responsible for tau hyperphosphorylation, in wild-type mice.DiscussionThese data suggest that lomerizine attenuates LPS-mediated neuroinflammatory responses and tau hyperphosphorylation and is a potential drug for neuroinflammation- or tauopathy-associated diseases.
Background: Residual neuromuscular blockade (RNMB) is a frequent event after general anesthesia, which can lead to serious complications, such as upper airway obstruction. Sugammadex is useful in reversing RNMB. However, its use in infants has not yet been approved by the Food and Drug Administration. Therefore, anesthesiologists can be hesitant use it, even in situations where no other choice is available.Case: A two-month-old baby presented to the hospital for umbilical polypectomy. At the end of the surgery, neostigmine was administered. Even after waiting for 30 min and injecting an additional dose of neostigmine, neuromuscular blockade was not adequately reversed. Eventually, sugammadex was administered, and spontaneous breathing returned.Conclusions: If there were no particular causes of delayed return to spontaneous breathing in infants, RNMB should be considered and reversal with sugammadex would be useful.
Background: The entanglement of multiple central venous catheters is a rare and serious complication. The Swan-Ganz catheter is a responsible for various cases. Case: A 66-year-old male patient was under general anesthesia for a coronary artery bypass graft surgery. As he had a pre-existing Perm catheter in the right subclavian vein, a Swan-Ganz catheter was inserted into the left internal jugular vein. Chest radiograph after catheter placement revealed that the Perm catheter had migrated to the left brachiocephalic vein. The surgeon attempted to reposition it manually, but postoperative radiograph showed that it had rolled into a loop. On postoperative day 1, radiological intervention was performed to untangle the loop, which was successful.Conclusions: After placing a Swan-Ganz catheter in patients with a pre-existing central venous catheter, the presence of entanglement should be assessed. In such cases, radiology-guided correction is recommended, as a blind attempt to disentangle can aggravate the condition.
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