Mention New York and you get a picture of the Brooklyn bridge
Mention Neurodegeneration and you get the brooklyn bridge of neurodegeneration. It is this picture showing axonal blebbing (green balloon) where the contents of the nerve escapes, because it has been cut. In the centre of an active MS lesion you can get over 10,000 blebs per square millimeter (Trapp et al. N. Eng J Med 1998. I may not be as bad as that so read on). So you want to stop those bleds forming.
DoctorLove works on on pathology and often talks about pre-active microglial lesions, it is suggest that some may develop into MS lesions and others resolve. In this mouse study, they find swollen axons as a forerunner to axonal damage that occur due to energy defects because of effects on the cells energy supplt. This is made in things called mitochondria. In this paper they use a neat bit of microscopy so they can look through cells and they can do this in living beasties to look into the brain or spinal cord. In the mice these axons die, but don’t need to show demyelination. This is perhaps not surprising because mice are pretty bad demyelinating models. Mice tend to lose nerves when attacked by inflammation. In this study they treated beasties that had evidence of nerve swelling, using agents that blocked the oxidative stress. This saved nerves. This swelling occurs in MS
How do they do this?….It’s not important because this needs a trial ,not self-experiment.
So there is a way to save nerves. Will there be a trial on this?. It seems to me like it is worth a try?
However after doing the post, thinking it was a new paper, I realised it is a decade old so it never went anywhere…Why Not?
In multiple sclerosis, a common inflammatory disease of the central nervous system, immune-mediated axon damage is responsible for permanent neurological deficits. How axon damage is initiated is not known. Here we use in vivo imaging to identify a previously undescribed variant of axon damage in a mouse model of multiple sclerosis. This process, termed ‘focal axonal degeneration‘ (FAD), is characterized by sequential stages, beginning with focal swellings and progressing to axon fragmentation. Notably, most swollen axons persist unchanged for several days, and some recover spontaneously. Early stages of FAD can be observed in axons with intact myelin sheaths. Thus, contrary to the classical view, demyelination-a hallmark of multiple sclerosis-is not a prerequisite for axon damage. Instead, focal intra-axonal mitochondrial pathology is the earliest ultrastructural sign of damage, and it precedes changes in axon morphology. Molecular imaging and pharmacological experiments show that macrophage-derived reactive oxygen and nitrogen species (ROS and RNS) can trigger mitochondrial pathology and initiate FAD. Indeed, neutralization of ROS and RNS rescues axons that have already entered the degenerative process. Finally, axonal changes consistent with FAD can be detected in acute human multiple sclerosis lesions. In summary, our data suggest that inflammatory axon damage might be spontaneously reversible and thus a potential target for therapy.
Disclaimer: please note that the opinions expressed here are those of the authors and do not reflect the positions of the Barts and the London School of Medicine and Dentistry, nor Barts Health NHS Trust or Queen Mary University London.