Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey

In vitro cultures of primary cortical neurons are widely used to investigate neuronal function.However,it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons,and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions.Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods,our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice.We used a microelectrode array technique to compare the electrophysiological differences in cortical neurons,and found that primary cortical neurons from the mouse brain began to show electrical activity earlier than those from the cynomolgus monkey.Although cultured monkey cortical neurons developed slowly in vitro,they exhibited typical pathological features-revealed by immunofluorescent staining-when infected with adeno-associated viral vectors expressing mutant huntingtin(HTT),the Huntington’s disease protein.A quantitative analysis of the cultured monkey cortical neurons also confirmed that mutant HTT significantly reduced the length of neurites.Therefore,compared with the primary cortical neurons of mice,cultured monkey cortical neurons have longer developmental and survival times and greater sustained physiological activity,such as electrophysiological activity.Our findings also suggest that primary cynomolgus monkey neurons cultured in vitro can simulate a cell model of human neurodegenerative disease,and may be useful for investigating time-dependent neuronal death as well as treatment via neuronal regeneration.All mouse experiments and protocols were approved by the Animal Care and Use Committee of Jinan University of China(IACUC Approval No.20200512-04)on May 12,2020.All monkey experiments were approved by the IACUC protocol(IACUC Approval No.LDACU 20190820-01)on August 23,2019 for animal management and use.

Concerned topics of epidural labor analgesia:labor elongation and maternal pyrexia:a systematic review

Objective:Labor is a complex process and labor pain presents challenges for analgesia.Epidural analgesia(EA)has a well-known analgesic effect and is commonly used during labor.This review summarized frequently encountered and controversial problems surrounding EA during labor,including the labor process and maternal intrapartum fever,to build knowledge in this area.Data sources:We searched for relevant articles published up to 2019 in PubMed using a range of search terms(eg,“labor pain,”“epidural,”“analgesia,”“labor process,”“maternal pyrexia,”“intrapartum fever”).Study selection:The search returned 835 articles,including randomized control trials,retrospective cohort studies,observational studies,and reviews.The articles were screened by title,abstract,and then full-text,with a sample independently screened by two authors.Thirty-eight articles were included in our final analysis;20 articles concerned the labor process and 18 reported on maternal pyrexia during EA.Results:Four classic prospective studies including 14,326 participants compared early and delayed initiation of EA by the incidence of cesarean delivery.Early initiation following an analgesia request was preferred.However,it was controversial whether continuous use of EA in the second stage of labor induced adverse maternal and neonatal outcomes due to changes in analgesic and epidural infusion regimens.There was a high incidence of maternal pyrexia in women receiving EA and women with placental inflammation or histologic chorioamnionitis compared with those receiving systemic opioids.Conclusions:Early EA(cervical dilation≥1 cm)does not increase the risk for cesarean section.Continuous epidural application of low doses of analgesics and programmed intermittent epidural bolus do not prolong second-stage labor duration or impact maternal and neonatal outcomes.The association between EA and maternal pyrexia remains controversial,but pyrexia is more common with EA than without.A non-infectious inflammatory process is an accepted mechanism of epidural-related maternal fever.