126 Chapter 5 lesioned areas. In cases where the origin of the infection was more unclear, there was a general increase of TSPO expression in activated microglia. HIVE brains showed perivascular TSPO+ infiltrates as well as TSPO+ microglial nodules and multinucleated giant cells. Studies to determine TSPO expression in infections of the central nervous systems have utilised PET imaging as reported for ZIKA182, and herpes encephalitis animal models183-185, as well as Creutzfeldt-Jakob disease patients177 but have not yet investigated expression in post-mortem tissues from humans. Neuropsychiatric disorders Several PET studies of TSPO as a marker of inflammation in psychiatric disorders have been performed but with differing outcomes. For example, PET studies in schizophrenia show different outcomes, either an increase, decrease, or no change compared to controls186. A recent review combining several meta-analyses187-189 showed that overall patients with schizophrenia have lowered TSPO concentrations compared to healthy individuals190. On the other hand, in depression, TSPO seems to be upregulated mostly in the anterior cingulate and prefrontal cortex178-180. TSPO was overall lower in depression patients receiving SSRI medication compared to unmedicated patients190. For bipolar disorder, an increase of TSPO mRNA and protein together with inflammasome activation was found in peripheral blood monocytes191. However, while an increasing number of studies show TSPO changes in neuropsychiatric disorders with TSPO PET, there is a paucity of data using human CNS tissues to determine the cellular expression of TSPO in neuropsychiatric disorders to substantiate findings of TSPO PET. Stroke TSPO PET in brain trauma could aid in monitoring regenerative processes after stroke. Depending on the region and severity of the infarct, TSPO is expressed to differing degrees by surrounding microglia and hypertrophic astrocytes. In a subacute infarct in the cerebellar cortex, TSPO+ microglia were found to be surrounding/ encapsulating Purkinje cells168. Epilepsy PET studies show increased binding of TSPO ligand in both ipsilateral and contralateral regions in temporal lobe epilepsy (TLE) suggesting inflammation distant to the seizure foci. Examination of brain tissue surgically resected revealed high TSPO expression in microglia and neurons and low expression in astrocytes181. FACS-RTT: A new technique to access the cellular origin of TSPO To measure TSPO overexpression, some studies have used histological staining135,150. However, even if this technique presents the advantage of an intact cellular architecture of the tissue, there is not enough quantitative precision to determine the contribution of each cell population of the brain in TSPO signal. Similarly, histological approaches do not allow to assess an important parameter: does an alteration of TSPO in the tissue result from the modulation of the number of cells expressing TSPO? Or does each cell produce more TSPO? To assess if the overexpression of TSPO is due to a cellular proliferation or an increased expression of TSPO in the cell, an innovative approach was recently developed192. This methodology combined the fluorescence-activated cell sorting (FACS) to isolate astrocytes,
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