Measuring Brain Loss

Carassiti D, Altmann DR, Petrova N, Pakkenberg B, Scaravilli F, Schmierer K.Neuronal loss, demyelination and volume change in the multiple sclerosis neocortex.Neuropathol Appl Neurobiol. 2017 doi: 10.1111/nan.12405. [Epub ahead of print]A IMS:Indices of brain volume (grey matter, white matter, lesions) are being used as outcomes in clinical trials of patients with multiple sclerosis (MS). We investigated the relationship between cortical volume, the number of neocortical neurons estimated using stereology, and demyelination.
METHODS:Nine MS and seven control hemispheres were dissected into coronal slices. On sections stained for Giemsa (a Dye), the cortex was outlined and optical disectors applied using systematic uniform random sampling. Neurons were counted using an oil immersion objective (x60) following stereological principles. Grey and white matter demyelination was outlined on myelin basic protein immuno-stained sections, and expressed as percentages of cortex and white matter, respectively.
RESULTS: In MS, the mean number of neurons was 14.9 ± 1.9 billion versus 24.4 ± 2.4 billion in controls (p < 0.011), a 39% difference. The density of neurons was smaller by 28% (p < 0.001), and cortical volume by 26% (p= 0.1). Strong association was detected between number of neurons and cortical volume (p < 0.0001). Demyelination affected 40 ± 13% of the MS neocortex and 9 ± 12% of the white matter, however neither correlated with neuronal loss. Only weak association was detected between number of neurons and white matter volume.
CONCLUSION:Neocortical neuronal loss in MS is massive and strongly predicted by cortical volume. Cortical volume decline detected in vivo may be similarly indicative of neuronal loss. Lack of association between neuronal density and demyelination suggests these features are partially independent, at least in chronic MS.

Yesterday we got the other half of the story that there was massive loss of spinal cord axons in the people tested in this study, but that the spinal cord was not shrinking. 

Now DrK and crew not happy with counting thousands of nerves want to count billions of nerves in the brain. In the individuals in this study they had lost 10,000,000,000 nerves.  But I suspect it 

I wonder what this would have been if highly effective treatments were available and used.

In this cases there was a better correlation with nerve content and the vloume of the cortex and perhaps supports the notion that Grey Matter Volume changes are a better biomarker for MRI studies.

This level of nerve loss did not correlate with demyelination however I think it shows that with time the nerve damage eleswhere eventually leads to loss of the whole nerve.

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  • How about this on BBC news today:

    Scientists hope they have found a drug to stop all neurodegenerative brain diseases, including dementia.
    In 2013, a UK Medical Research Council team stopped brain cells dying in an animal for the first time, creating headline news around the world.
    But the compound used was unsuitable for people, as it caused organ damage.
    Now two drugs have been found that should have the same protective effect on the brain and are already safely used in people.
    "It's really exciting," said Prof Giovanna Mallucci, from the MRC Toxicology Unit in Leicester.
    She wants to start human clinical trials on dementia patients soon and expects to know whether the drugs work within two to three years.
    Why might they work?
    The novel approach is focused on the natural defence mechanisms built into brain cells.
    When a virus hijacks a brain cell it leads to a build-up of viral proteins.
    Cells respond by shutting down nearly all protein production in order to halt the virus's spread.
    Many neurodegenerative diseases involve the production of faulty proteins that activate the same defences, but with more severe consequences.
    The brain cells shut down production for so long that they eventually starve themselves to death.
    This process, repeated in neurons throughout the brain, can destroy movement, memory or even kill, depending on the disease.
    It is thought to take place in many forms of neurodegeneration, so safely disrupting it could treat a wide range of diseases.
    In the initial study, the researchers used a compound that prevented the defence mechanism kicking in.
    It halted the progress of prion disease in mice – the first time any neurodegenerative disease had been halted in any animal.
    Further studies showed the approach could halt a range of degenerative diseases.
    The findings were described as a "turning point" for the field even though the compound was toxic to the pancreas.
    A neurodegenerative disease is one in which the cells of the brain and spinal cord are lost
    The functions of these cells include decision making and control of movements
    These cells are not easily regenerated, so the effects of diseases can be devastating
    Neurodegenerative diseases include Alzheimer's, Parkinson's, multiple sclerosis and Huntington's
    Source: London Brain Centre

    • Thanks Barbara.

      Looking forward to Team G's tale on this one…

      Is the neuro-protective add-on around the corner at last?

      Will this molecule kill Laquinimod?

      Tony F

    • Reading more about it, it is still pre-human trials!

      Meanwhile, keeping up with turmeric and pure liquorice won't hurt by the looks of it (DBA compound). Mind you too much liquorice will raise your blood pressure, so careful there.

      Tony F

    • Described as a "wonder drug", completely irresponsible IMO. Not sure going to be of much relevance to MS but I'll try and keep an open mind.

    • Posted…don't hold your breath just yet. By the time it gets to MS laquinimod will be flying high or it will be long gone.

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