Enhanced Pain Relief with Guanfacine as an Adjuvant for Trigeminal Nerve Blocks: Insights from a PheWAS-Guided Randomized Controlled Study.

Background: Trigeminal neuralgia and painful trigeminal neuropathy are severely painful conditions which are often difficult to treat with medications. A Phenome-Wide Association Study (PheWAS) analysis identified an association between single nucleotide variants in the alpha-2 adrenergic receptor (ADRA2) subtype B, a G protein-coupled receptor expressed on peripheral and central presynaptic terminals, and an increased risk for trigeminal nerve disorders. We hypothesized that adding the ADRA2 agonist guanfacine to routine care trigeminal nerve injections would provide enhanced pain relief in trigeminal neuralgia than routine care alone.

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-β Associated Neurodegenerative Pathways and Glial Signatures in a Mouse Model of Alzheimer's Disease: A Targeted Transcriptome Analysis.

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer's disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 () is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them.

Arginase 1 Insufficiency Precipitates Amyloid- Deposition and Hastens Behavioral Impairment in a Mouse Model of Amyloidosis.

Alzheimer's disease (AD) includes several hallmarks comprised of amyloid- (Aβ) deposition, tau neuropathology, inflammation, and memory impairment. Brain metabolism becomes uncoupled due to aging and other AD risk factors, which ultimately lead to impaired protein clearance and aggregation. Increasing evidence indicates a role of arginine metabolism in AD, where arginases are key enzymes in neurons and glia capable of depleting arginine and producing ornithine and polyamines.

Reflections on Data Sharing Practices in Spinal Cord Injury Research.

There are few pharmacological therapeutics available for spinal cord injury despite years of preclinical and clinical research. This brief editorial discusses some of the shortcomings of translational research efforts. In addition, we comment on our previous experiences with data curation and highlight evolving efforts by the spinal cord injury research community to improve prospects for future therapeutic development, especially pertaining to preclinical data sharing through the Open Data Commons for Spinal Cord Injury (ODC-SCI).

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.

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses.

Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research.

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.

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.