Cytosolic phospholipase A2 in infiltrating monocyte derived macrophages does not impair recovery after spinal cord injury in female mice.

Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation and persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery.

Nonresolving Neuroinflammation Regulates Axon Regeneration in Chronic Spinal Cord Injury.

Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse and facilitate axon retraction away from lesion boundaries. Little is known about the role of sustained inflammation in chronic SCI or whether chronic inflammation affects regeneration.

Cytosolic Phospholipase A2 in Infiltrating Monocyte-Derived Macrophages Does Not Impair Recovery After Spinal Cord Injury in Female Mice.

Spinal cord injury (SCI) leads to permanent motor and sensory loss that is exacerbated by intraspinal inflammation that persists months to years after injury. After SCI, monocyte-derived macrophages (MDMs) infiltrate the lesion to aid in myelin-rich debris clearance. During debris clearance, MDMs adopt a proinflammatory phenotype that exacerbates neurodegeneration and hinders recovery.

Non-resolving neuroinflammation regulates axon regeneration in chronic spinal cord injury.

Chronic spinal cord injury (SCI) lesions retain increased densities of microglia and macrophages. In acute SCI, macrophages induce growth cone collapse, facilitate axon retraction away from lesion boundaries, as well as play a key role in orchestrating the growth-inhibitory glial scar. Little is known about the role of sustained inflammation in chronic SCI, or whether chronic inflammation affects repair and regeneration.

PTEN knockout using retrogradely transported AAVs transiently restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and transiently restore locomotor functions in near-complete injury models.

PTEN knockout using retrogradely transported AAVs restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and restore locomotor functions in near-complete injury models.

Advanced Age and Neurotrauma Diminish Glutathione and Impair Antioxidant Defense after Spinal Cord Injury.

Advanced age at the time of spinal cord injury (SCI) exacerbates damage from reactive oxygen species (ROS). Mechanisms underlying this age-dependent response are not well understood and may arise from decreased antioxidant defense. We investigated how spinal cord levels of the antioxidant glutathione (GSH), and its regulation, change with age and SCI.

Immunoglobulin G Is Increased in the Injured Spinal Cord in a Sex- and Age-Dependent Manner.

There are limited studies examining age and sex as biological variables in the pathophysiology of spinal cord injury (SCI). The use of older animals and sex-balanced groups in SCI models is increasingly prioritized to better match clinical demographics. Including older animals in SCI studies is technically challenging, and outcomes are unpredictable with respect to biological and treatment responses.

The effects of myelin on macrophage activation are phenotypic specific via cPLA in the context of spinal cord injury inflammation.

Spinal cord injury (SCI) produces chronic, pro-inflammatory macrophage activation that impairs recovery. The mechanisms driving this chronic inflammation are not well understood. Here, we detail the effects of myelin debris on macrophage physiology and demonstrate a novel, activation state-dependent role for cytosolic phospholipase-A2 (cPLA) in myelin-mediated potentiation of pro-inflammatory macrophage activation.

Mitochondria exert age-divergent effects on recovery from spinal cord injury.

The extent that age-dependent mitochondrial dysfunction drives neurodegeneration is not well understood. This study tested the hypothesis that mitochondria contribute to spinal cord injury (SCI)-induced neurodegeneration in an age-dependent manner by using 2,4-dinitrophenol (DNP) to uncouple electron transport, thereby increasing cellular respiration and reducing reactive oxygen species (ROS) production. We directly compared the effects of graded DNP doses in 4- and 14-month-old (MO) SCI-mice and found DNP to have increased efficacy in mitochondria isolated from 14-MO animals.

Corrigendum: Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury.

[This corrects the article DOI: 10.3389/fneur.2020.

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury.

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients.

Effect of Sex on Motor Function, Lesion Size, and Neuropathic Pain after Contusion Spinal Cord Injury in Mice.

Spinal cord injury (SCI) causes neurodegeneration, impairs locomotor function, and impacts the quality of life particularly in those individuals in whom neuropathic pain develops. Whether the time course of neurodegeneration, locomotor impairment, or neuropathic pain varies with sex, however, remains understudied. Therefore, the objective of this study in male and female C57BL/6 mice was to evaluate the following outcomes for six weeks after a 75-kdyn thoracic contusion SCI: locomotor function using the Basso Mouse Scale (BMS); spinal cord tissue sparing and rostral-caudal lesion length; and mechanical allodynia and heat hyperalgesia using hindpaw application of Von Frey filaments or radiant heat stimuli, respectively.

Delayed Azithromycin Treatment Improves Recovery After Mouse Spinal Cord Injury.

After spinal cord injury (SCI), macrophages infiltrate into the lesion and can adopt a wide spectrum of activation states. However, the pro-inflammatory, pathological macrophage activation state predominates and contributes to progressive neurodegeneration. Azithromycin (AZM), an FDA approved macrolide antibiotic, has been demonstrated to have immunomodulatory properties in a variety of inflammatory conditions.

Opportunities for Self-Evaluation Increase Student Calibration in an Introductory Biology Course.

Accurate self-evaluation is critical for learning. Calibration describes the relationship between learners' perception of their performance and their actual performance on a task. Here, we describe two studies aimed at assessing and improving student calibration in a first-semester introductory biology course at a 4-year public institution.

Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury.

Central neuropathic pain develops in greater than 75% of individuals suffering a spinal cord injury (SCI). Increasingly, sex is recognized as an important biological variable in the development and treatment of peripheral neuropathic pain, but much less is known about the role of sex in central neuropathic pain and its pharmacological inhibition. To test the hypothesis that efficacy of analgesic therapies differs between males and females in SCI, we used a mouse model of SCI pain to determine the analgesic efficacy of pioglitazone (PIO), U.

Reducing age-dependent monocyte-derived macrophage activation contributes to the therapeutic efficacy of NADPH oxidase inhibition in spinal cord injury.

Objective: The average age at the time of spinal cord injury (SCI) has increased to 43 years old. Middle-aged mice (14 months old, MO) exhibit impaired recovery after SCI with age-dependent increases in reactive oxygen species (ROS) production through NADPH oxidase (NOX) along with pro-inflammatory macrophage activation. Despite these aging differences, clinical therapies are being examined in individuals regardless of age based upon preclinical data generated primarily using young animals (∼4 MO).

Compression Decreases Anatomical and Functional Recovery and Alters Inflammation after Contusive Spinal Cord Injury.

Experimental models of spinal cord injury (SCI) typically utilize contusion or compression injuries. Clinically, however, SCI is heterogeneous and the primary injury mode may affect secondary injury progression and neuroprotective therapeutic efficacy. Specifically, immunomodulatory agents are of therapeutic interest because the activation state of SCI macrophages may facilitate pathology but also improve repair.

Pioglitazone treatment following spinal cord injury maintains acute mitochondrial integrity and increases chronic tissue sparing and functional recovery.

Pioglitazone is an FDA-approved PPAR-γ agonist drug used to treat diabetes, and it has demonstrated neuroprotective effects in multiple models of central nervous system (CNS) injury. Acute treatment after spinal cord injury (SCI) in rats is reported to suppress neuroinflammation, rescue injured tissues, and improve locomotor recovery. In the current study, we additionally assessed the protective efficacy of pioglitazone treatment on acute mitochondrial respiration, as well as functional and anatomical recovery after contusion SCI in adult male C57BL/6 mice.

Age increases reactive oxygen species production in macrophages and potentiates oxidative damage after spinal cord injury.

Age potentiates neurodegeneration and impairs recovery from spinal cord injury (SCI). Previously, we observed that age alters the balance of destructive (M1) and protective (M2) macrophages; however, the age-related pathophysiology in SCI is poorly understood. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) contributes to reactive oxygen species (ROS)-mediated damage and macrophage activation in neurotrauma.

Azithromycin drives alternative macrophage activation and improves recovery and tissue sparing in contusion spinal cord injury.

Background: Macrophages persist indefinitely at sites of spinal cord injury (SCI) and contribute to both pathological and reparative processes. While the alternative, anti-inflammatory (M2) phenotype is believed to promote cell protection, regeneration, and plasticity, pro-inflammatory (M1) macrophages persist after SCI and contribute to protracted cell and tissue loss. Thus, identifying non-invasive, clinically viable, pharmacological therapies for altering macrophage phenotype is a challenging, yet promising, approach for treating SCI.

Clinical safety of the ProMRI pacemaker system in patients subjected to thoracic spine and cardiac 1.5-T magnetic resonance imaging scanning conditions.

Background: Permanent cardiac pacemakers have historically been considered a contraindication to magnetic resonance imaging (MRI).

Objective: The purpose of the ProMRI Phase B Study, a multicenter, prospective, single-arm, nonrandomized study, was to evaluate the clinical safety of the Biotronik ProMRI pacemaker system in patients undergoing thoracic spine and cardiac MRI.

Methods: The ProMRI Phase B study enrolled 245 patients with stable baseline pacing indices implanted with an Entovis pacemaker (DR-T or SR-T) and Setrox 53-cm and/or 60-cm lead(s).

Age decreases macrophage IL-10 expression: Implications for functional recovery and tissue repair in spinal cord injury.

Macrophages with different activation states are present after spinal cord injury (SCI). M1 macrophages purportedly promote secondary injury processes while M2 cells support axon growth. The average age at the time of SCI has increased in recent decades, however, little is known about how different physiological factors contribute to macrophage activation states after SCI.