Method of the Week
Fling, B. W., Dutta, G. G., Schlueter, H., Cameron, M. H., & Horak, F. B. (2014). Associations between Proprioceptive Neural Pathway Structural Connectivity and Balance in People with Multiple Sclerosis. Frontiers in Human Neuroscience, 8. https://doi.org/10.3389/fnhum.2014.00814
As the first study to utilize diffusion imaging to identify white matter tracts of MS positive patients that compromise the cortical proprioceptive pathways, it was found that MS patients had reduced white matter integrity. Specifically in the cortical proprioceptive tract. It was also found with confidence that microstructural integrity of this pathway in the right hemisphere was strongly related to proprioceptive-based balance control in both MS patients and age-matched control participants. In the healthy control group, white matter integrity of the pathway was significantly correlated with overall balance. The same relationship was diminished in MS patients. It was speculated that balance control in MS patients may become more dependent on cerebellar-regulated proprioceptive control, the vestibular system, and/or the visual system. This was tested through balancing procedures. Whether their eyes were closed or whether they were standing on foam was varied.
Filippi, M., Cercignani, M., Inglese, M., Horsfield, M. A., & Comi, G. (2001). Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology, 56(3), 304–311. https://doi.org/10.1212/wnl.56.3.304
This study suggests that DTI can effectively identify severe tissue damage in MS lesions, detect changes in NAWM, and provide valuable insights into the clinical disability of MS patients, particularly in the context of secondary progressive MS. It may also have a role in monitoring advanced stages of the disease. Key findings include: lesions in MS patients had higher mean diffusivity (MD) and lower fractional anisotropy (FA) compared to NAWM, enhanced lesions had lower FA values compared to non-enhanced lesions, T1-hypointense lesions had different MD and FA values compared to T1-isointense lesions, NAWM in MS patients had different MD and FA values compared to white matter in healthy controls, there were significant correlations between lesion volume, MD, and FA values of both lesions and NAWM, in the overall patient group, there was a moderate correlation between lesion volume and the Expanded Disability Status Scale score, and this correlation was stronger in patients with secondary progressive MS, where disability was also correlated with average lesion FA.
Schikorski, D., Cuvillier-Hot, V., Leippe, M., Boidin-Wichlacz, C., Slomianny, C., Macagno, E., Salzet, M., & Tasiemski, A. (2008). Microbial Challenge Promotes the Regenerative Process of the Injured Central Nervous System of the Medicinal Leech by Inducing the Synthesis of Antimicrobial Peptides in Neurons and Microglia. The Journal of Immunology, 181(2), 1083–1095. https://doi.org/10.4049/jimmunol.181.2.1083
In this article, the scientists studied the regenerative process of CNS after trauma and how it is enhanced by a controlled bacterial infection, suggesting that induction of regeneration of normal CNS function may depend critically upon the co-initiation of an immune response. They had three treatment groups with damaged CNS: sterile, live bacteria, and killed bacteria. In the sterile environment, a weak connection returned after 8 days. In the live bacteria environment, bacteria was allowed to live, move, and replicate with no interruption. While the CNS began reparation, it quickly got weaker and weaker as the bacteria was allowed to thrive. Finally, in the hypothesized and last group, the bacteria were introduced in a set amount and quickly heated to extinction, so that the immune response was triggered without being depleted. This group showed significant reparation with the CNS, unlike the other two groups. As far as the biology behind the repair, two newly characterized antimicrobial peptides were shown to be produced by microglial cells and by neurons themselves in response to a CNS injury: Hm-lumbricin and neuromacin. These peptides, in addition to exerting antimicrobial properties, appeared to promote the neural repair of the leech CNS.
Zhu, Q., Whittemore, S. R., Devries, W. H., Zhao, X., Kuypers, N. J., & Qiu, M. (2011). Dorsally-derived oligodendrocytes in the spinal cord contribute to axonal myelination during development and remyelination following focal demyelination. Glia, 59(11), 1612–1621. https://doi.org/10.1002/glia.21203
Zhu and his colleagues experimented with oligodendrocytes, a cell type that plays a major part in myelination. Most OPCs develop in the ventral ventricular zone; however, recent studies suggested that a small number of OPCs can also be generated in the dorsal spinal cord. It is not clear whether these dorsal oligodendrocyte precursor cells participate in myelination and remyelination. To study the use of these cells, the scientists used Cre-lox genetic fate mapping in transgenic mice. They produced a focal demyelination injury. In response, a large number of newly differentiated oligodendrocytes originated from dOLs (dorsal oligodendrocytes), suggesting that dOLs may provide an important source of OPCs for axonal remyelination in multiple sclerosis or spinal cord injury.
B Ferguson, M K Matyszak, M M Esiri, V H Perry. (2011). Axonal damage in acute multiple sclerosis lesions., Brain, Volume 120, Issue 3, Pages 393–399, https://doi.org/10.1093/brain/120.3.393
One of the histological hallmarks of early multiple sclerosis lesions is primary demyelination, with myelin destruction and relative sparing of axons. On the other hand, it is widely accepted that axonal loss occurs in, and is responsible for, the permanent disability characterizing the later chronic progressive stage of the disease. In this study, they used an antibody against amyloid precursor protein, known to be a sensitive marker of axonal damage in a number of other contexts, in immunocytochemical experiments on paraffin embedded multiple sclerosis lesions of varying ages in order to see at which stage of the disease axonal damage, in addition to demyelination, occurs and may thus contribute to the development of disability in patients.
Duffy, S. S., Perera, C. J., Preet G S Makker, Lees, J. G., Pascal Carrive, & Gila Moalem-Taylor. (2016). Peripheral and Central Neuroinflammatory Changes and Pain Behaviors in an Animal Model of Multiple Sclerosis. Frontiers in Immunology, 7. https://doi.org/10.3389/fimmu.2016.00369
In this study, the scientists used the animal model experimental autoimmune encephalomyelitis (EAE) to examine both stimulus-evoked and spontaneous pain behaviors, and neuroinflammatory changes, over the course of the chronic disease. They looked at a Hind Paw Mechanical Allodynia, Facial Mechanical Allodynia, and a mouse grimace scale. Measurement of spontaneous pain using the mouse grimace scale, a facial expression-based coding system, showed increased facial grimacing in mice with EAE during clinical disease. This was associated with multiple peripheral and central neuroinflammatory changes including a decrease in myelinating oligodendrocytes, increased T cell infiltration, and macrophage/microglia and astrocyte activation. For the hind paw mechanical allodynia, it was the worst in the first few days and a couple days before the onset of the disease. For the facial mechanical allodynia, its progression peaked around day 10-13. Their body weight also drastically dropped around day 10. Overall, these findings suggest that different pathological mechanisms may underlie stimulus-evoked and spontaneous pain in EAE, and that these behaviors predominate in unique stages of the disease. For the hind paw mechanical allodynia, it was the worst in the first few days and a couple days before the onset of the disease.