Wednesday, 22 March 2017

Imaging hot microglia.

Datta G, Colasanti A, Kalk N, Owen DR, Scott G, Rabiner EI, Gunn R, Lingford-Hughes A, Malik O, Ciccarelli O, Nicholas R, Nie L, Battaglini M, De Stefano N, Matthews P.
[11C]PBR28 or [18F]PBR111 detect white matter inflammatory heterogeneity in multiple sclerosis.J Nucl Med. 2017. pii: jnumed.116.187161. doi: 10.2967/jnumed.116.187161. [Epub ahead of print]
Objective: To assess microglial activation in lesions and in normal appearing white matter of multiple sclerosis (MS) patients using positron emission tomography (PET). 
Methods: 34 MS patients (7 with secondary progressive MS (SPMS), 27 with relapsing remitting MS (RRMS)) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO), binding status underwent PET scanning with TSPO radioligands (11C-PBR28 or 18F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudo-reference region). White matter lesions (WML) were classified as "active" (DVR highest in the lesion), "peripherally active" (peri-lesional DVR highest), "inactive" (DVR highest in surrounding normal appearing white matter, NAWM) or "undifferentiated" (similar DVR across lesion, peri-lesional and NAWM volumes). 
Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4x10-11). A higher proportion of lesions were inactive in patients with SPMS (35 %) than RRMS (23 %), but active lesions were found in all patients, including those on highly efficacious treatments. 
Conclusion: TSPO radioligand uptake was increased in brains of MS patients relative to healthy controls with two TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. 

Translocator protein (TSPO) is an 18 kDa protein mainly found on the outer mitochondrial membrane. It was first described as peripheral benzodiazepine receptor (PBR), a secondary binding site for diazepam, but subsequent research has found the receptor to be expressed throughout the body and brain.

TSPO has been proposed to interact with StAR (steroidogenic acute regulatory protein) to transport cholesterol into mitochondria. It has been suggested to be a marker of microglial activation. 

In this study they reported more activity in MS and found lesions in relapsing and SPMS and the lesions were more active in relapsing rather than SPMS, but still there are active lesions. So as we have been saying, RRMS and SPMS are not distinct. 

However, it gives an indication of the presence of hot microglia, it  seems increasingly evident that there is a broader activity than just microglia so we have to interpret the data more cautiously

1 comment:

  1. This hot microglia business...

    Having found out that I was low on iron after a ferritin test (blood cell count showed nothing) and since I'm feeling much better again having adjusted my diet and taken iron supplements, I started doing some reading about iron in MS.

    I thought that some of the information on the interaction of microglia, iron and oligodendrocytes here was fascinating: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402663/

    I'd be interested to know any thoughts on iron.

    I will certainly be making sure I am never low on iron again. It is very easy for a woman to become low on iron.

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