Chondroitinase ABC (ChABC) represents a promising therapeutic strategy for the treatment of spinal cord injury due to its potent effects on restoring function to spinal-injured adult mammals. However, there is limited mechanistic insight as to the underlying effects of ChABC treatment, where the effects are mediated, and which signaling pathways are involved in ChABC-mediated repair. Here we use a transgenic (YFP-H) mouse to demonstrate that cortical layer V projection neurons undergo severe atrophy 4 weeks after thoracic dorsal column injury and that ChABC is neuroprotective for these neurons after ICV infusion. ChABC also prevented cell atrophy after localized delivery to the spinal cord, suggesting a possible retrograde neuroprotective effect mediated at the injury site. Furthermore, neuroprotection of corticospinal cell somata coincided with increased axonal sprouting in the spinal cord. In addition, Western blot analysis of a number of kinases important in survival and growth signaling revealed a significant increase in phosphorylated ERK1 at the spinal injury site after in vivo ChABC treatment, indicating that activated ERK may play a role in downstream repair processes after ChABC treatment. Total forms of PKC and AKT were also elevated, indicating that modification of the glial scar by ChABC promotes long-lasting signaling changes at the lesion site. Thus, using the YFP-H mouse as a novel tool to study degenerative changes and repair after spinal cord injury we demonstrate, for the first time, that ChABC treatment regulates multiple signaling cascades at the injury site and exerts protective effects on axotomized corticospinal projection neurons.

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General anaesthesia for obstetric surgery has distinct characteristics that may contribute towards a higher risk of accidental awareness during general anaesthesia. The primary aim of this study was to investigate the incidence, experience and psychological implications of unintended conscious awareness during general anaesthesia in obstetric patients. From May 2017 to August 2018, 3115 consenting patients receiving general anaesthesia for obstetric surgery in 72 hospitals in England were recruited to the study. Patients received three repetitions of standardised questioning over 30 days, with responses indicating memories during general anaesthesia that were verified using interviews and record interrogation. A total of 12 patients had certain/ probable or possible awareness, an incidence of 1 in 256 (95%CI 149-500) for all obstetric surgery. The incidence was 1 in 212 (95%CI 122-417) for caesarean section surgery. Distressing experiences were reported by seven (58.3%) patients, paralysis by five (41.7%) and paralysis with pain by two (16.7%). Accidental awareness occurred during induction and emergence in nine (75%) of the patients who reported awareness. Factors associated with accidental awareness during general anaesthesia were: high BMI (25-30 kg.m -2 ); low BMI (<18.5 kg.m -2 ); out-of-hours surgery; and use of ketamine or thiopental for induction. Standardised psychological impact scores at 30 days were significantly higher in awareness patients (median (IQR [range]) 15 (2.7-52.0 [2-56]) than in patients without awareness 3 (1-9 [0-64]), p = 0.010. Four patients had a provisional diagnosis of post-traumatic stress disorder. We conclude that direct postoperative questioning reveals high rates of accidental awareness during general anaesthesia for obstetric surgery, which has implications for anaesthetic practice, consent and follow-up.

By reading this article, you should be able to: Describe the pathogenesis of sickle cell disease (SCD). Recognise the acute complications that occur in children with SCD. Illustrate the key issues in the perioperative management of a child with SCD. Explain the available strategies and rationale behind multimodal analgesia for children with SCD presenting with acute pain. Sickle cell disease (SCD) is an inherited disorder with multisystem complications, often presenting in childhood. 1 Anaesthetists are frequently involved throughout perioperative care, in the management of acute pain and acute complications. SCD results from inheriting genes coding for an abnormal b-globin chain from both parents, where at least one is the sickle cell gene. Sickle cell anaemia (SCA), the most severe and common form of SCD, results from inheriting sickle bglobin genes from both parents, leading to a homozygous HbSS state. 2,3 Other disease forms include heterozygous states involving other abnormal b-globin alleles such as b-thalassaemia (HbSß), C (HbSC), and D-punjabi (HbSD). Inheriting one sickle cell and one normal haemoglobin gene leads to sickle cell trait (SCT), which usually has no clinical consequences. SCD is a significant global public health issue. The WHO reports that the sickle cell gene is responsible for more than 80% of all inherited haemoglobinopathies, with 85% of SCD cases in Africa. 4 SCD also occurs in the Mediterranean, Arabia, South Asia, and elsewhere mainly as a result of migration. 3,4 The distribution of SCD closely matches the distribution of malaria, because the heterozygous states are protective against Plasmodium falciparum infection. 4 However, those with SCA are more susceptible, and more likely to develop lifethreatening malaria. There is a disparity between the availability of healthcare resources for the treatment of SCD relative to its geographical distribution. Resources are most limited in many African Sonia Akrimi FRCA MRCP PGCME is a speciality trainee in anaesthesia in the Health Education Kent, Surrey and Sussex Deanery. She has interests in medical education and global surgery.