Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone.

Although new neurons are produced in the subventricular zone (SVZ) of the adult mammalian brain, fewer functional neurons are produced with increasing age. The age-related decline in neurogenesis has been attributed to a decreased pool of neural progenitor cells (NPCs), an increased rate of cell death, and an inability to undergo neuronal differentiation and develop functional synapses. The time between mitotic events has also been hypothesized to increase with age, but this has not been directly investigated. Studying primary-cultured NPCs from the young adult and aged mouse forebrain, we observe that fewer aged cells are dividing at a given time; however, the mitotic cells in aged cultures divide more frequently than mitotic cells in young cultures during a 48-hour period of live-cell time-lapse imaging. Double-thymidine-analog labeling also demonstrates that fewer aged cells are dividing at a given time, but those that do divide are significantly more likely to re-enter the cell cycle within a day, both in vitro and in vivo. Meanwhile, we observed that cellular survival is impaired in aged cultures. Using our live-cell imaging data, we developed a mathematical model describing cell cycle kinetics to predict the growth curves of cells over time in vitro and the labeling index over time in vivo. Together, these data surprisingly suggest that progenitor cells remaining in the aged SVZ are highly proliferative.

Bipolar Radiofrequency Neurotomy of the Genicular Nerves for Chronic Pain Due to Knee Osteoarthritis.

Background: The current treatments for chronic knee osteoarthritis (OA), a disabling and costly healthcare condition in the United States, vary in their level of supporting evidence. Although total knee replacement is one of the best-supported interventions, its associated risks should not be taken lightly, especially in older patients with comorbidities. Genicular nerve block with subsequent genicular nerve radiofrequency neurotomy (GN-RFN) has emerged as a promising intervention for refractory pain in knee OA. Purposes/Questions: We sought to assess the pain and functional outcomes of genicular nerve bipolar radiofrequency neurotomy (B-RFN) for the treatment of chronic pain due to knee OA. Methods: A total of 21 patients who underwent unilateral genicular nerve B-RFN after positive diagnostic genicular nerve block (50% or greater pain relief) treated between July 2018 to December 2018 were included. Pain numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were collected at baseline, 3 months, and 6 months post-B-RFN. Changes at each time point were compared to baseline scores using paired sample t tests. Results: At 3 months, 62% of patients had a greater than 50% improvement in NRS scores and 57% of patients had a greater than 50% improvement in WOMAC scores. At 6 months, 81% of patients had a greater than 50% improvement in NRS scores and 67% had a greater than 50% improvement in WOMAC scores. The absolute change in mean NRS (± standard deviation) at 6 months went from 7.5 ± 1.9 to 2.5 ± 1.2. The absolute change in mean WOMAC scores at 6 months went from 46.9 ± 8.0 to 19.0 ± 6.2. Conclusion: Of 21 patients, 14 (67%) saw greater than 50% improvements in both NRS and WOMAC scores at 6 months after genicular nerve B-RFN. Further prospective studies are needed to determine the selection criteria of patients most likely to benefit from this procedure.

Investigation of genicular neurotomy of the knee: MRI characterization of anatomy and implications for intervention.

BACKGROUND: Genicular nerve block and subsequent radiofrequency neurotomy (RFN) has emerged as a novel intervention and alternative for total knee arthroplasty in patients with refractory pain from knee osteoarthritis (OA). To our knowledge, there is no cited report correlating the accuracy of localizing the genicular nerves using bony landmarks on magnetic resonance imaging (MRI). OBJECTIVES: To quantify the proximity of superomedial genicular nerve (SMGN), superolateral genicular nerve (SLGN), and inferomedial genicular nerve (IMGN) from a target point. The target point was an intersection marked by a line parallel to the diaphysis and a separate line parallel to the metaphyseal flare along the cortical surfaces of both the femur and tibia. DESIGN: Retrospective chart review. PATIENTS: A total of 25 de-identified knee MRIs were reviewed. METHODS: The coronal proton density fat suppressed sequence was used for identification and localization of the SLGN, SMGN, and IMGN. The neurovascular bundles were traced from posterior location along their origin as they wrap around the distal diaphysis. The nerve locations were determined by consensus measurements performed by two board-certified radiologists with certificates of added qualification in neuroradiology and interventional radiology. The proximity of each respective genicular nerves was measured by drawing a perpendicular line from each genicular nerve to the height of the target point. All measurements were taken on the mid-coronal view at the point of maximal epiphyseal flare. MAIN OUTCOME MEASUREMENTS: Positive values indicated the location of the neurovascular bundle to be superior to the target point. Negative values indicated the location of the neurovascular bundle to be inferior to the target point. RESULTS: The distance between our target point and the inferior border of SLGN ranged from -3 mm to 6 mm. Twenty-three out of 25 (92%) SLGN lied exactly at or above our target intersection. The distance between our target point and the inferior border of SMGN ranged from -1 mm to 2 mm with twenty-two out of 25 (88%) SMGN lied exactly at or above our target point. The distance between our target point and the superior border of IMGN ranged from 0 mm to 3 mm with all (100%) IMGN lying exactly at or above the target point. CONCLUSION: The intersection of the femoral diaphyseal shaft to a line along the metaphyseal flare and the intersection of the tibial diaphyseal shaft to a line along the medial metaphyseal can be used as a target point to localize the genicular nerves with close proximity.