Gender and race in neurotrauma: part 1-identifying inequalities in leadership, academics, and clinical trial management.

Gender and racial equality, or the lack thereof, is a constantly recurring theme in neurosurgery and under-reported in neurotrauma literature. This perspective piece addresses the underrepresentation and challenges faced by women and racial minorities in neurosurgery, and within the workforce of neurotrauma, specifically. The literature demonstrates that there is still a scarcity of females and racial minorities in neurosurgery leadership positions and that females are less likely to receive invited papers.

Heterogeneity of synaptic NMDA receptor responses within individual lamina I pain-processing neurons across sex in rats and humans.

Excitatory glutamatergic NMDA receptors (NMDARs) are key regulators of spinal pain processing, and yet the biophysical properties of NMDARs in dorsal horn nociceptive neurons remain poorly understood. Despite the clinical implications, it is unknown whether the molecular and functional properties of synaptic NMDAR responses are conserved between males and females or translate from rodents to humans. To address these translational gaps, we systematically compared individual and averaged excitatory synaptic responses from lamina I pain-processing neurons of adult Sprague-Dawley rats and human organ donors, including both sexes.

Progeria-based vascular model identifies networks associated with cardiovascular aging and disease.

Hutchinson-Gilford Progeria syndrome (HGPS) is a lethal premature aging disorder caused by a de novo heterozygous mutation that leads to the accumulation of a splicing isoform of Lamin A termed progerin. Progerin expression deregulates the organization of the nuclear lamina and the epigenetic landscape. Progerin has also been observed to accumulate at low levels during normal aging in cardiovascular cells of adults that do not carry genetic mutations linked with HGPS.

Cannabinoid CB1 Receptor Expression and Localization in the Dorsal Horn of Male and Female Rat and Human Spinal Cord.

Background: Preclinical and clinical evidence suggests that cannabis has potential analgesic properties. However, cannabinoid receptor expression and localization within spinal cord pain processing circuits remain to be characterized across sex and species.

Aims: We aimed to investigate the differential expression of the cannabinoid type 1 (CB1) receptor across dorsal horn laminae and cell populations in male and female adult rats and humans.

Perceived Utility of Intracranial Pressure Monitoring in Traumatic Brain Injury: A Seattle International Brain Injury Consensus Conference Consensus-Based Analysis and Recommendations.

Background: Intracranial pressure (ICP) monitoring is widely practiced, but the indications are incompletely developed, and guidelines are poorly followed.

Objective: To study the monitoring practices of an established expert panel (the clinical working group from the Seattle International Brain Injury Consensus Conference effort) to examine the match between monitoring guidelines and their clinical decision-making and offer guidance for clinicians considering monitor insertion.

Methods: We polled the 42 Seattle International Brain Injury Consensus Conference panel members' ICP monitoring decisions for virtual patients, using matrices of presenting signs (Glasgow Coma Scale [GCS] total or GCS motor, pupillary examination, and computed tomography diagnosis).

A cellular taxonomy of the adult human spinal cord.

The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding of spinal cellular diversity, characterizing human biology directly is important to uncover specialized features of basic function and human pathology. Here, we present a cellular taxonomy of the adult human spinal cord using single-nucleus RNA sequencing with spatial transcriptomics and antibody validation.

Using Clinical Vignettes and a Modified Expert Delphi Panel to Determine Parameters for Identifying Non-Traumatic Spinal Cord Injury in Health Administrative and Electronic Medical Record Databases.

Objective: To obtain expert consensus on the parameters and etiologic conditions required to retrospectively identify cases of non-traumatic spinal cord injury (NTSCI) in health administrative and electronic medical record (EMR) databases based on the rating of clinical vignettes.

Design: A modified Delphi process included 2 survey rounds and 1 remote consensus panel. The surveys required the rating of clinical vignettes, developed after chart reviews and expert consultation.

Projected timeline to achieve gender balance within the United States neurosurgical workforce exceeds 150 years: a National Plan and Provider Enumeration System analysis.

Objective: Despite incremental progress in the representation and proportion of women in the field of neurosurgery, female neurosurgeons still represent an overwhelming minority of the current US physician workforce. Prior research has predicted the timeline by which the proportion of female neurosurgery residents may reach that of males, but none have used the contemporary data involving the entire US neurosurgical workforce.

Methods: The authors performed a retrospective analysis of the National Plan and Provider Enumeration System (NPPES) registry of all US neurosurgeons to determine changes in the proportions of women in neurosurgery across states, census divisions, and census regions between 2010 and 2020.

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain.

The prevalence and severity of many chronic pain syndromes differ across sex, and recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn, direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund's adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between KCC2-dependent disinhibition and N-methyl-D-aspartate receptor (NMDAR) potentiation within superficial dorsal horn neurons was observed in male but not female rats.

Fibrinogen aptamer functionalized gold-coated iron-oxide nanoparticles for targeted imaging of thrombi.

Targeting of molecular constituents of thrombi with aptamer functionalized core-shell nanoparticles (CSN) allowed for high resolution clot delineation in T2-weighted magnetic resonance imaging. Meanwhile, the gold-coating demonstrated sufficient contrast capabilities in computed tomography (1697 HU μM). This targeted CSN formulation could allow for precise imaging of blood clots at low nanomolar concentrations.

A Randomized Controlled Trial of Local Delivery of a Rho Inhibitor (VX-210) in Patients with Acute Traumatic Cervical Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) can result in severe, lifelong neurological deficits. After SCI, Rho activation contributes to collapse of axonal growth cones, failure of axonal regeneration, and neuronal loss. This randomized, double-blind, placebo-controlled phase 2b/3 study evaluated the efficacy and safety of Rho inhibitor VX-210 (9 mg) in patients after acute traumatic cervical SCI.

Analysis of human satellite cell dynamics on cultured adult skeletal muscle myofibers.

Background: Maintaining stem cells in physiologically relevant states is necessary to understand cell and context-specific signalling paradigms and to understand complex interfaces between cells in situ. Understanding human stem cell function is largely based on tissue biopsies, cell culture, and transplantation into model organisms.

Methods: Here, we describe a method to isolate post-mortem intact human muscle myofibers and culture muscle stem cells within the niche microenvironment to assay cellular dynamics, stem cell identity, stem cell hierarchy, and differentiation potential.

Exploring the Unique Contrast Properties of Aptamer-Gadolinium Conjugates in Magnetic Resonance Imaging for Targeted Imaging of Thrombi.

: An important clinical question in the determination of the extent of thrombosis-related vascular conditions is the identification of blood clot location. Fibrin is a major molecular constituent of blood clots and can, therefore, be utilized in molecular imaging. In this proof-of-concept study, we sought to prepare a fibrin-targeting magnetic resonance imaging contrast agent, using a Gd(III)-loaded fibrinogen aptamer (FA) chelate conjugate (Gd(III)-NOTA-FA) (NOTA = 1,4,7-triazacyclononane-1,4,7-triacetic acid), to endow the ability to specifically accumulate at the location of blood clots, thereby enhancing contrast capabilities.

Assessment of Aptamer-Targeted Contrast Agents for Monitoring of Blood Clots in Computed Tomography and Fluoroscopy Imaging.

Random formation of thrombi is classified as a pathological process that may result in partial or complete obstruction of blood flow and limited perfusion. Further complications include pulmonary embolism, thrombosis-induced myocardial infraction, ischemic stroke, and others. Location and full delineation of the blood clot are considered to be two clinically relevant aspects that could streamline proper diagnosis and treatment follow-up.

Factors Associated with Recovery in Motor Strength, Walking Ability, and Bowel and Bladder Function after Traumatic Cauda Equina Injury.

Traumatic cauda equina injury (TCEI) is usually caused by spine injury at or below L1 and can result in motor and/or sensory impairments and/or neurogenic bowel and bladder. We examined factors associated with recovery in motor strength, walking ability, and bowel and bladder function to aid in prognosis and establishing rehabilitation goals. The analysis cohort was comprised of persons with acute TCEI enrolled in the Rick Hansen Spinal Cord Injury Registry.

A Guide to Extract Spinal Cord for Translational Stem Cell Biology Research: Comparative Analysis of Adult Human, Porcine, and Rodent Spinal Cord Stem Cells.

Improving the clinical translation of animal-based neural stem/progenitor cell (NSPC) therapies to humans requires an understanding of intrinsic human and animal cell characteristics. We report a novel method to assess spinal cord NSPCs from a small (rodent) and large (porcine) animal model in comparison to human NSPCs. To extract live adult human, porcine, and rodent spinal cord tissue, we illustrate a strategy using an anterior or posterior approach that was simulated in a porcine model.

Design and evaluation of a biosynthesized cellulose drug releasing duraplasty.

Decompressive craniectomy (DC) is a standard surgical procedure performed on stroke patients in which a portion of a skull is removed and a duraplasty membrane is applied onto the brain. While DC can significantly reduce the risk of death, it does not reverse the stroke damage. In this study, a novel biosynthesized cellulose (BC)-based drug releasing duraplasty was developed and studied.

Loss of STEP61 couples disinhibition to N-methyl-d-aspartate receptor potentiation in rodent and human spinal pain processing.

Dysregulated excitability within the spinal dorsal horn is a critical mediator of chronic pain. In the rodent nerve injury model of neuropathic pain, BDNF-mediated loss of inhibition (disinhibition) gates the potentiation of excitatory GluN2B N-methyl-d-aspartate receptor (NMDAR) responses at lamina I dorsal horn synapses. However, the centrality of this mechanism across pain states and species, as well as the molecular linker involved, remain unknown.

Insights into the suitability of utilizing brown rats (Rattus norvegicus) as a model for healing spinal cord injury with epidermal growth factor and fibroblast growth factor-II by predicting protein-protein interactions.

The stimulation of the proliferation and differentiation of neural stem cells (NSCs) offers the possibility of a renewable source of replacement cells to treat numerous neurological diseases including spinal cord injury, traumatic brain injury and stroke. Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) have been used to stimulate NSCs to renew, expand, and produce precursors for neural repair within an adult brown rat (Rattus norvegicus). To provide greater insight into the interspecies protein-protein interactions between human FGF-2 and EGF proteins and native R.

Increased Prevalence of Chronic Disease in Back Pain Patients Living in Car-dependent Neighbourhoods in Canada: A Cross-sectional Analysis.

Objectives: Chronic diseases, including back pain, result in significant patient morbidity and societal burden. Overall improvement in physical fitness is recommended for prevention and treatment. Walking is a convenient modality for achieving initial gains.