Kinetics and voltage dependence of inactivation of a prokaryotic voltage-gated sodium channel (NaChBac) were investigated in an effort to understand its molecular mechanism. NaChBac inactivation kinetics show strong, bell-shaped voltage dependence with characteristic time constants ranging from approximately 50 ms at depolarized voltages to a maximum of approximately 100 s at the inactivation midpoint. Activation and inactivation parameters for four different covalently linked tandem dimer or tandem tetramer constructs were indistinguishable from those of the wild-type channel. Point mutations in the outer part of the pore revealed an important influence of the S195 residue on the process of inactivation. For two mutants (S195D and S195E), the maximal and minimal rates of inactivation observed were increased by approximately 2.5-fold, and the midpoint of the steady-state inactivation curve was shifted approximately 20 mV in the hyperpolarizing direction, compared to the wild-type channel. Our data suggest that pore vestibule structure is an important determinant of NaChBac inactivation, whereas the inactivation mechanism is independent of the number of free cytoplasmic N- and C-termini in the functional channel. In these respects, NaChBac inactivation resembles C-type or slow inactivation modes observed in other voltage-gated K and Na channels.

A single intrathecal injection of 0.2 mg of morphine safely reduces postoperative pain following lumbar fusion.

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Background Research efforts have been focused on limiting secondary injury after traumatic spinal cord injury by performing spinal decompression and early optimization of spinal cord perfusion. The Winnipeg Intraspinal Pressure Monitoring Study (WISP) was designed to validate the technique of intraspinal pressure monitoring at the site of injury using a fiberoptic pressure monitor placed at the site of injury. Objectives To describe the design of the WISP study. Study design Descriptive. Methods We explain the current limitations in the available scientific literature around the topic of blood pressure management for acute traumatic spinal cord injury and rational for the WISP study. Then, we describe the design of WISP including the patient selection criteria, study interventions, follow up schedules and outcome measurements. A multitude of future research avenues are also discussed. Results The WISP study is a single center pilot study designed to validate the technique of intraspinal pressure monitoring following acute traumatic spinal cord injury. The study involves the measurement of intraspinal pressure from within the subarachnoid space at the site of injury to derive a number of physiological parameters including spinal cord perfusion pressure, spinal cord blood volume, measures of spinal cord compliance and vascular reactivity indices. Twenty eligible patients will be recruited and followed for a period of 12 months with visits scheduled for the first 5 days and 1, 3, 6, and 12 months following surgical intervention. Conclusions The WISP study will provide the first attempt in North America at validation of intraspinal pressure monitoring with a fiberoptic pressure monitor at the site of injury. Successful validation will lead to future studies to define optimal spinal cord perfusion pressure, relationships of neural injury biomarkers and outcomes as well as epigenetic studies. Trial registration This study has been registered at clinicaltrials.gov (registration# NCT04550117).

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Hypertonic saline (HTS) is a commonly administered agent for intracranial pressure (ICP) control in traumatic brain injury (TBI). The literature on its use is mainly in moderate/severe TBI where invasive ICP monitoring is present. The role of HTS in patients with moderate TBI (mTBI) outside of the intensive care unit (ICU) setting remains unclear. The goal of this scoping review was to provide an overview of the available literature on HTS administration in patients with mTBI without ICP monitoring, assessing its impact on outcome and transitions in care. We performed a scoping systematic review of the literature of MEDLINE, Embase, Scopus, BIOSIS, and the Cochrane Databases from inception to July 31, 2020. We searched for those published articles documenting the administration of HTS in patients with mTBI with recorded functional outcome or transitions in hospital care. A two-step review process was conducted in accordance with methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions . There were many studies with combined moderate/severe TBI populations. However, most failed to document subgroup analysis for patients with mTBI. Our search strategy identified only one study that documented the administration of HTS in mTBI in which subgroup analysis for mTBI and outcomes were provided. This retrospective cohort study assessed patients with mTBI who did/did not receive prophylactic HTS, finding that those not receiving HTS demonstrated a deterioration in Glasgow Coma Scale (GCS) score in the first 48 h. However, the HTS group did demonstrate a trend to longer hospital stay and pneumonia. Our scoping review identified a significant gap in knowledge surrounding the use of HTS for patients with mTBI without invasive ICP monitoring. The limited identified literature suggests prophylactic administration prevents clinical deterioration, although this is based on a single study with data available for mTBI sub-analysis. Further studies on HTS in non-monitored patients with mTBI are required.