| {Sridharan, 2019 #2124} MS patients, blocking study, 45% specific signal, low brain penetration (VT of 0.29 / 0.17 ml/cm3), [18F]GE-180 exhibits a specific signal in the brain [16]. |
(요약그림 in Zhou 2021). TSPO in cerebral vessels of normal mice was found to provide a major binding site for 11C-PK11195, 11C-PBR28 and 18F-FEDAA1106, in contrast to no overt specific binding of 18F-FEBMP and 11C-Ac5216 to this vascular component. 18F-FEBMP yielded PET images of microglial TSPO with a higher contrast than 11C-PK11195 in a tau transgenic mouse modeling AD) and allied neurodegenerative tauopathies | ||
| metabolism |
{Cumming, 2018 #2126}2nd : [18F]GE180 metabolites constituted less than 10% of brain radioactivity.136 Species difference (rodent shows good BBB permeability), Low SB in human brain 138, 139 | {Janssen, 2016 #2113} rat unfortunately? (although rapid metabolism in plasma) in brain still 85–90% of tracer was intact 15–30 min p.i. [71], | {MacAskill, 2021 #2115}Rat favorable metabolism, less than 12.7% radiometabolites were measured in the brain, heart, and lung at 60 and 120 min after administration |
CNS-Resident Macrophages (CRM)
| Microglia | Border-associated macrophages (BAM) | |
|---|---|---|
| location | parechyma | choroid plexus, dural and subdural meninges, and are adjacent to the vasculature within the perivascular space12 |
| origin | Both CRM populations arise from early erythron myeloid progenitor cells in the fetal yolk sac but segregate by day E10.5 into two distinct populations | |
| function | ||
| marker | ||
Microglia
- resident macrophage cells, 그러나 macrophage 와 gene expression profile 이 다소 다르다.
- constitute about 5-20% of all glial cells (원래 peripheral 에서도 monocyte 가 macrophage 로 되는 검)
origin:
- erythromyeloid cells from the embryonic yolk sac as their progenitors,
- These progenitors colonize the brain during the first trimester of fetal development, in both rodents, and humans, then mature into microglia
(CF: PBMC의 대부분은 Lymphocyte 임 https://www.researchgate.net/post/PBMC_cell_types_frequencies)
turnover:
- instead of constantly being replaced with myeloid progenitor cells, the microglia maintain their status quo while in their quiescent state, and then, when they rapidly proliferate in order to keep their numbers up activation by Microglia can be activated by a variety of factors including: pro-inflammatory cytokines, cell necrosis factors, lipopolysaccharide, and changes in extracellular potassium (indicative of ruptured cells).
Structure of microglia
| Cytoplasam | |
| Nuclei | |
| Mitochondria | |
| ER | |
| GOLGI compex | |
| Lysosome (and lipid droplet) | |
| Centrioles |
Phenotypes of microglia
| A | B | C | D | |
|---|---|---|---|---|
| Resting ramified | Intermediate reactive | reactive | Amoeboid | |
| {Rodríguez-Chinchilla, 2020 #2163} AAV-haSyn (nigral) rat | ramified | Hyper-ramified | bushy |
Substantia Nigra · AAV-ha-syn (a)
- y-axis: % of Iba-1+ cells
- x-axis groups: 2w p.i. / 3w p.i. / 16w p.i., bars labelled A B C D within each group
| {??, 2020 #2452} | Striatum | ||||
|---|---|---|---|---|---|
| Ramified | Primed | Activated | Amoeboid | Non-microglial | |
Striatum legends and plots (b, c)
- legend: Ramified / Primed / Activated / Amoeboid / Non-microglial
- b: LPS, y-axis “Number of Iba-1+ cells”, x-axis Days (Intact, 1, 7, 14)
- c: 6-OHDA, y-axis “Number of Iba-1+ cells”, x-axis Days (Intact, 1, 7, 14)
| SNpc | ||||
|---|---|---|---|---|
| Ramified | Primed | Activated | Amoeboid | |
SNpc legends and plots (e, f)
- legend: Ramified / Primed / Activated / Amoeboid
- e: LPS, y-axis “Number of Iba-1+ cells”, x-axis Days (Intact, 1, 7, 14)
- f: 6-OHDA, y-axis “Number of Iba-1+ cells”, x-axis Days (Intact, 1, 7, 14)
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Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Sridharan row | low brain penetration (V_T of 0.29 / 0.17 ml/cm^3) | The two numerals after V_T of are partially obscured by red highlight; reading is 0.29 over a 0.17-like value but cannot be confirmed unit by unit. |
| Cumming row | radioactivity.136 | The trailing .136 is small; could read as a footnote marker rather than a decimal. |
| Lower microscopy citation | {??, 2020 #2452} | Author surname before , 2020 #2452 is too small to read; entry is uncertain. |
| Janssen row | (although rapid metabolism in plasma) in brain still 85–90% of tracer was intact 15–30 min p.i. [71], | Closing parenthesis after plasma is faint; sentence boundary may differ from rendering. |