Characterization of neuroinflammatory positron emission tomography biomarkers in chronic traumatic encephalopathy.
Brain Commun
; 4(1): fcac019, 2022.
Article
em En
| MEDLINE
| ID: mdl-35198978
ABSTRACT
Chronic traumatic encephalopathy is a neurological disorder associated with head trauma and is confirmed upon autopsy. PET imaging of chronic traumatic encephalopathy may provide a means to move towards ante-mortem diagnosis and therapeutic intervention following brain injuries. Characterization of the neuroinflammatory PET biomarkers, 18â
kDa translocator protein and monoamine oxidase-B was conducted using [3H]PBR-28 and [3H]L-deprenyl, respectively, in post-mortem chronic traumatic encephalopathy brain tissue. [3H]PBR-28 displayed high specific binding in both chronic traumatic encephalopathy (95.40 ± 1.87%; n = 11 cases) and healthy controls (89.89 ± 8.52%, n = 3 cases). Cell-type expression of the 18â
kDa translocator protein was confirmed by immunofluorescence to microglia, astrocyte and macrophage markers. [3H]L-deprenyl also displayed high specific binding in chronic traumatic encephalopathy (96.95 ± 1.43%; n = 12 cases) and healthy controls (93.24 ± 0.43%; n = 2 cases), with the distribution co-localized to astrocytes by immunofluorescence. Saturation analysis was performed to quantify the target density of the 18â
kDa translocator protein and monoamine oxidase-B in both chronic traumatic encephalopathy and healthy control tissue. Using [3H]PBR-28, the target density of the 18â
kDa translocator protein in healthy controls was 177.91 ± 56.96â
nM (n = 7 cases; mean ± standard deviation); however, a highly variable target density (345.84 ± 372.42â
nM; n = 11 cases; mean ± standard deviation) was measured in chronic traumatic encephalopathy. [3H]L-deprenyl quantified a monoamine oxidase-B target density of 304.23 ± 115.93â
nM (n = 8 cases; mean ± standard deviation) in healthy control tissue and is similar to the target density in chronic traumatic encephalopathy tissues (365.80 ± 128.55â
nM; n = 12 cases; mean ± standard deviation). A two-sample t-test determined no significant difference in the target density values of the 18â
kDa translocator protein and monoamine oxidase-B between healthy controls and chronic traumatic encephalopathy (P > 0.05), albeit a trend towards increased expression of both targets was observed in chronic traumatic encephalopathy. To our knowledge, this work represents the first in vitro characterization of 18â
kDa translocator protein and monoamine oxidase-B in chronic traumatic encephalopathy and reveals the variability in neuroinflammatory pathology following brain injuries. These preliminary findings will be considered when designing PET imaging studies after brain injury and for the ultimate goal of imaging chronic traumatic encephalopathy in vivo.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Brain Commun
Ano de publicação:
2022
Tipo de documento:
Article