Augmented expression of TSPO after intracerebral hemorrhage: a role in inflammation?

Abstract

BackgroundIntracerebral hemorrhage (ICH) is a potentially fatal stroke subtype accounting for 10–15 % of all strokes. Despite neurosurgical intervention and supportive care, the 30-day mortality rate remains 30–50 % with ICH survivors frequently displaying neurological impairment and requiring long-term assisted care. Although accumulating evidence demonstrates the role of neuroinflammation in secondary brain injury and delayed fatality after ICH, the molecular regulators of neuroinflammation remain poorly defined after ICH.MethodsIn the present study, ICH was induced in CD1 male mice by collagenase injection method and given the emerging role of TSPO (18-kDa translocator protein) in neuroinflammation, immunofluorescence staining of brain sections was performed to characterize the temporal expression pattern and cellular and subcellular localization of TSPO after ICH. Further, both genetic and pharmacological studies were employed to assess the functional role of TSPO in neuroinflammation.ResultsThe expression of TSPO was found to be increased in the peri-hematomal brain region 1 to 7 days post-injury, peaking on day 3 to day 5 in comparison to sham. Further, the TSPO expression was mostly observed in microglia/macrophages, the inflammatory cells of the central nervous system, suggesting an unexplored role of TSPO in neuroinflammatory responses after ICH. Further, the subcellular localization studies revealed prominent perinuclear expression of TSPO after ICH. Moreover, both genetic and pharmacological studies revealed a regulatory role of TSPO in the release of pro-inflammatory cytokines in a macrophage cell line, RAW 264.7.ConclusionsAltogether, the data suggest that TSPO induction after ICH could be an intrinsic mechanism to prevent an exacerbated inflammatory response and raise the possibility of targeting TSPO for the attenuation of secondary brain injury after ICH.

Intracerebral delivery of the M2 polarizing cytokine interleukin 13 using mesenchymal stem cell implants in a model of temporal lobe epilepsy in mice

“…Recent studies have reported that expression of TSPO may be driven to resolve inflammation 31 and that it is expressed on CD206-positive cells (marker of M2) in a mouse model of neuroinflammation induced by intracerebral hemorrhage. 32 At the same time, TSPO was also co-localized with CD16/32-positive cells (a marker of M1) in this model. Thus, it can be suggested that both M1-and M2-activated cells may express TSPO and that TSPO expression may not be solely a marker of a proinflammatory reaction in the brain.…”

“…However, our data suggest that even M2‐activated microglia/macrophages may express high levels of TSPO, which we later confirmed by TSPO and Ym1 double immunofluorescence staining. Recent studies have reported that expression of TSPO may be driven to resolve inflammation and that it is expressed on CD206‐positive cells (marker of M2) in a mouse model of neuroinflammation induced by intracerebral hemorrhage . At the same time, TSPO was also co‐localized with CD16/32‐positive cells (a marker of M1) in this model.…”

In vivo monitoring of remnant undifferentiated neural cells following human induced pluripotent stem cell-derived neural stem/progenitor cells transplantation

“…For example, there is a dramatic increase in inflammation and associated activation of TSPO‐expressing microglia after TBI or SCI . Moreover, it has been reported that the activated Iba1 + microglia, which present a major cellular source of TSPO, peaks 42 days post‐SCI while TSPO expression peaks within a week or 72 hours after infarction, especially in the cerebral infarction models and the brain injury models, respectively . In order to elucidate time‐dependent changes of TSPO expression after SCI in rodent models, we analyzed the gene expression of TSPO in mice at the nine days marker and 42 days marker after SCI using microarray.…”

Microglial Activation in Traumatic Brain Injury

“…In a mouse model of intracranial hemorrhage, microglia exclusively expressed TSPO and in these cells CD16/32 (M1-like) or CD206 (M2-like) were evenly distributed (Bonsack et al, 2016). …”