Role of Facial Nerve Reconstruction With Anastomosis and Polyglycolic Acid Tube in Accelerating Functional Recovery After Axotomy in the Rat Facial Nucleus.

Facial nerve injuries stem from trauma or tumor surgery, triggering neurodegeneration and neuronal cell death in the facial nucleus, consequently inducing irreversible nerve paralysis. Following facial nerve transection, glial cells are activated and undergo proliferation, facilitating motor neuron survival, repair, and regeneration. Clinical approaches, including nerve anastomosis and hypoglossal nerve grafting, require delicate microscopic techniques. Recent advancements involve nerve reconstruction using polyglycolic acid (PGA) tubes, which yield nerve function improvement. However, the central pathophysiological effects of these procedures remain unclear. Therefore, using PGA tubes, we evaluated neurodegeneration and microglial inflammatory response in rats after facial nerve transection. Facial nerve functions were evaluated using vibrissae and blink reflex scores. In the end-to-end anastomosis and PGA tube reconstruction groups, a partial improvement in facial motor function was observed, with increased nerve fiber survival in the former. Approximately 90% of neurons survived in both groups, wherein gliosis exhibited increased microglial activation compared to that in the transection group. These results indicate that PGA tube-assisted nerve reconstruction post-facial nerve transection, although inferior to end-to-end anastomosis, improved certain functions and prevented neuronal cell death. Furthermore, the prolonged inflammatory response in the facial nerve nucleus underscored the correlation between neuronal function and survival and microglia.

Macrophage depletion attenuates degeneration of spiral ganglion neurons in kanamycin-induced unilateral hearing loss model.

Pathological conditions in cochlea, such as ototoxicity, acoustic trauma, and age-related cochlear degeneration, induce cell death in the organ of Corti and degeneration of the spiral ganglion neurons (SGNs). Although macrophages play an essential role after cochlear injury, its role in the SGNs is limitedly understood. We analyzed the status of macrophage activation and neuronal damage in the spiral ganglion after kanamycin-induced unilateral hearing loss in mice. The number of ionized calcium-binding adapter molecule 1 (Iba1)-positive macrophages increased 3 days after unilateral kanamycin injection. Macrophages showed larger cell bodies, suggesting activation status. Interestingly, the number of activating transcription factor 3 (ATF3)-positive-neurons, an indicator of early neuronal damage, also increased at the same timing. In the later stages, the number of macrophages decreased, and the cell bodies became smaller, although the number of neuronal deaths increased. To understand their role in neuronal damage, macrophages were depleted via intraperitoneal injection of clodronate liposome 24 h after kanamycin injection. Macrophage depletion decreased the number of ATF3-positive neurons at day 3 and neuronal death at day 28 in the spiral ganglion following kanamycin injection. Our results suggest that suppression of inflammation by clodronate at early timing can protect spiral ganglion damage following cochlear insult.

Diagnostic Utility of 99m Tc-MDP Bone Scintigraphy for Nivolumab-Induced Inflammatory Arthritis.

ABSTRACT: Immune checkpoint inhibitors can revive exhausted helper T-cells, and inflammatory cell reactivation may cause autoimmune disease-like conditions. Drug-induced arthritis is an immune-related adverse event, but the diagnostic approach is undefined. We present the diagnostic utility of 99m Tc-MDP bone scintigraphy for nivolumab-induced inflammatory arthritis. A 67-year-old man with hypopharyngeal carcinoma presented bilateral multiple metacarpophalangeal joint pain and swelling at each nivolumab administration. Regular imaging findings were atypical for inflammatory arthritis and did not fulfill the criteria for rheumatoid arthritis. We diagnosed nivolumab-induced inflammatory arthritis based on clinical symptoms and the symmetrical moderate uptake of the affected joints on 99m Tc-MDP bone scintigraphy.

Deletion of CD38 and supplementation of NAD+ attenuate axon degeneration in a mouse facial nerve axotomy model.

Following facial nerve axotomy, nerve function is not fully restored even after reconstruction. This may be attributed to axon degeneration/neuronal death and sustained neuroinflammation. CD38 is an enzyme that catalyses the hydrolysis of nicotinamide adenine dinucleotide (NAD+) and is a candidate molecule for regulating neurodegeneration and neuroinflammation. In this study, we analyzed the effect of CD38 deletion and NAD+ supplementation on neuronal death and glial activation in the facial nucleus in the brain stem, and on axon degeneration and immune cell infiltration in the distal portion of the facial nerve after axotomy in mice. Compared with wild-type mice, CD38 knockout (KO) mice showed reduced microglial activation in the facial nucleus, whereas the levels of neuronal death were not significantly different. In contrast, the axon degeneration and demyelination were delayed, and macrophage accumulation was reduced in the facial nerve of CD38 KO mice after axotomy. Supplementation of NAD+ with nicotinamide riboside slowed the axon degeneration and demyelination, although it did not alter the level of macrophage infiltration after axotomy. These results suggest that CD38 deletion and supplementation of NAD+ may protect transected axon cell-autonomously after facial nerve axotomy.

Decreased activity of daily living produced by the combination of Alzheimer's disease and lower limb fracture in elderly requiring nursing care.

OBJECTIVES: Alzheimer's disease (AD) impairs cognitive functions, subsequently decreasing activity of daily living (ADL), and is frequently accompanied by lower limb fracture including hip fracture in the elderly. However, there have been few studies on what kinds of physical functions are affected or what degrees of dysfunction are produced by this combination. This study aims to clarify the relationship between decreased ADL and the combination of AD and lower limb fracture. METHODS: We examined present illness and ADL in 4340 elderly aged 82.8 ± 9.36 years [average ± standard deviation (SD)] requiring nursing care and compared ADL between elderly with and without AD or lower limb fracture treated with surgery or conservatively using analysis of covariance (ANCOVA), with age and sex as covariants. RESULTS: We recognized that activities of cognitive function (p < 0.001), eating (dysphagia) (p < 0.001), eating (feeding) (p < 0.001), and toilet use (p < 0.001) in the elderly with AD were significantly lower than in those without the disease, even after adjusting for sex and age. Activities of bed mobility (p < 0.05), transfer and locomotion (p < 0.001), and bathing (p < 0.05) in the elderly with a fracture treated with surgery were significantly lower, which differed from the results of AD. Significant interactions of AD and fracture treated with surgery on the ADL scores for bed mobility (p < 0.001), dysphagia (p < 0.01), feeding (p < 0.001), and toilet use (p < 0.05) show that the combination had a much more profound influence on the ADL scores than AD or fracture alone. We obtained almost the same results for fractures treated conservatively as for fractures treated with surgery. CONCLUSIONS: These results demonstrated that the combined effects of AD and lower limb fracture were significantly greater than expected additive effects of AD and fracture, suggesting that the combination of AD and lower limb fracture has synergistic effects on almost all types of ADL except cognitive functions.