The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.
BackgroundSmall animal models that can mimic degenerative disc disease (DDD) are commonly used to examine DDD progression. However, assessments such as histological studies and macroscopic measurements do not allow for longitudinal studies because they can only be completed after the animal is sacrificed. Dynamic contrast-enhanced MRI (DCE-MRI) may provide a reliable, non-invasive in vivo method for detecting the progression.MethodsThe present study investigated the progression of changes in lumbar discs and the effect of endplate conditions on diffusion into the lumbar discs of aging sand rats after intravenous administration of gadolinium-containing contrast medium through the tail vein. Contrast enhancement was measured in the lumbar intervertebral discs on each image. The results were compared with those from conventional histological characterizations.ResultsT2-weighted images revealed that with aging, the shape of L3–L4, L4–L5, L5–L6, and L6–S1 nucleus pulposus (NP) became irregular, while the mean areas, signal intensities, and T2 values of the NP were significantly decreased. Each of the observed disc changes demonstrated a progressive increase in phase during 2-min scout scans. Post-contrast MRI showed impaired endplate nutritional diffusion to the disc with aging, enhancement was significantly greater in young animals than in old animals. Endplate calcification or sclerosis was histologically confirmed; histologic score was correlated with the age. We found the histological score of the endplate negatively corresponded to the DCE-MRI results.ConclusionsDCE-MRI studies offer a non-invasive in vivo method for investigating the progress of diffusion into the discs and the functional conditions of the endplate. We conclude that quantitative DCE-MRI can identify the severity of disc degeneration and efficiently reflect the progression of vertebral endplate changes in the aging sand rat lumbar spine via the NP contrast enhancement patterns.
The preoperative degeneration of the adjacent segment of the disc is a significant risk factor for ASD.
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