Loss of integrity of the Blood Brain Barrier in the striata of patients with PD

[ElliotGreen]

Postmortem investigation find loss of integrity of the BBB in the striata of patients with PD.

ncbi.nlm.nih.gov/pmc/articl...

They can't say for sure whether the increased permeability of the blood brain barrier preceded Parkinson's disease, or was caused by it. But they hypothesize that it comes first and may play a role in the development of Parkinson's disease.

"The present study shows a loss of integrity of the BBB in the striata of patients with PD. This is consistent with evidence for BBB dysfunction in an increasing number of neurodegenerative disorders, including Alzheimer's disease, amyotrophic lateral sclerosis, and chronic traumatic encephalopathy. The postmortem nature of this study renders interpretation of the temporal aspects of this dysfunction difficult.

"However, given increasing evidence that α-synuclein aggregation is initiated at the level of axon terminals it is tempting to speculate that altered BBB permeability in the striatum precedes the development of nigral/cortical Lewy body disease. We believe that this would allow blood-borne substances to reach the axon terminals of striatopetal neurons and initiate aggregation of α-synuclein. Further studies in model organisms such as mice or nonhuman primates will allow assessment of this hypothesis."

[ElliotGreen]

This changes my doubts about mannitol somewhat.

I have previously expressed my doubt about the potential efficacy of mannitol as a treatment for Parkinson's disease.

healthunlocked.com/parkinso...

To be effective, and agent needs to 1) get through the BBB and 2) dissolve dissolve clumps of alpha-synuclein (or it least present clumps from forming). I will consider these in reverse order.

Mannitol apparently does present new clumps of alpha-synuclein from forming, although I do not believe there is evidence that it dissolves existing clumps.

It is unclear whether it makes it through the blood brain barrier in oral doses.

The Israeli research and published claims relied upon the ability of mannitol to DISRUPT the BBB. They injected rodents with enough mannitol to do so. But oral amounts of mannitol taken by humans would not be sufficient to disrupt the blood brain barrier, nor would it really be wise to do so on a regular basis, because that would expose the brain to all sorts of toxins.

However, if the blood brain barrier in the area of the striatum is already permeable in people with Parkinson's (as this article suggests), then oral doses of mannitol may actually be able to reach the alpha synuclein in the striatum.

The article I linked to above says, "The dense innervation of the striatum by PD-affected regions allows for exploitation of this permeability for therapeutic goals." But I don't see that they elaborate.

[LAJ12345 in reply to ElliotGreen]

So I guess that means many compounds that aren’t supposed to be able to be absorbed by the brain might actually be able to.Perhaps the extent of the breach varies for each individual so does it explain why eg thiamine is required in different amounts by different people I wonder?

[sharoncrayn]

I have a completely different take versus yours on this "in vivo" lab study on the permeability of the BBB. Nothing positive about it IMO.

[JAS9]

One doctor / nutritionist's take on how to improve both BBB's integrity and blood flow to the brain: youtu.be/t-noCw4LsY4(Not working as expected?)