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.
TSPO (18 kDa translocator protein) was identified decades ago in a search for peripheral tissue binding sites for benzodiazepines, and was formerly called the peripheral benzodiazepine receptor. TSPO is a conserved protein throughout evolution and it is implicated in the regulation of many cellular processes, including inflammatory responses, oxidative stress, and mitochondrial homeostasis. TSPO, apart from its broad expression in peripheral tissues, is highly expressed in neuroinflammatory cells, such as activated microglia. In addition, emerging studies employing the ligands of TSPO suggest that TSPO plays an important role in neuropathological settings as a biomarker and therapeutic target. However, the precise molecular function of this protein in normal physiology and neuropathology remains enigmatic. This review provides an overview of recent advances in our understanding of this multifaceted molecule and identifies the knowledge gap in the field for future functional studies.
Intracerebral hemorrhage (ICH) is a subtype of stroke which is associated with the highest mortality and morbidity rates of all strokes. Although it is a major public health problem, there is no effective treatment for ICH. As a consequence of ICH, various blood components accumulate in the brain parenchyma and are responsible for much of the secondary brain damage and ICH-induced neurological deficits. Therefore, the strategies that could attenuate the blood component-induced neurotoxicity and improve hematoma resolution are highly needed. The present article provides an overview of blood-induced brain injury after ICH and emphasizes the need to conduct further studies elucidating the mechanisms of hematoma resolution after ICH.
Intracerebral hemorrhage (ICH) is a devastating type of stroke with a substantial public health impact. Currently, there is no effective treatment for ICH. The purpose of the study was to evaluate whether the post-injury administration of Resveratrol confers neuroprotection in a pre-clinical model of ICH. To this end, ICH was induced in adult male CD1 mice by collagenase injection method. Resveratrol (10 mg/kg) or vehicle was administered at 30 min post-induction of ICH and the neurobehavioral outcome, neurodegeneration, cerebral edema, hematoma resolution and neuroinflammation were assessed. The Resveratrol treatment significantly attenuated acute neurological deficits, neurodegeneration and cerebral edema after ICH in comparison to vehicle treated controls. Further, Resveratrol treated mice exhibited improved hematoma resolution with a concomitant reduction in the expression of proinflammatory cytokine, IL-1β after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.
Intracerebral hemorrhage (ICH) is a devastating sub-type of stroke with no proven treatment. Given the emerging role of Galectin-1 and Galectin-3 in neuroimmune responses, the objective of the current manuscript is to elucidate hemorrhagic-injury induced modulation and cellular expression of Galectin-1 and Galectin-3 in the brain in a pre-clinical model of ICH. To address this, ICH was induced in male CD1 mice by collagenase injection method. Western blotting as well as Immunofluorescence staining was performed to characterize the temporal expression pattern as well as cellular localization of Galectin-1 and Galectin-3 after ICH. Further, genetic studies were conducted to assess the functional role of Galectin-1 and Galectin-3 in inflammatory response employing a murine macrophage cell line, RAW 264.7. Galectin-1 and Galectin-3 exhibited very profound and increased expression from day 3 to day 7-postinjury, in the perihematomal brain region after ICH in comparison to Sham. Further, Galectin-1 expression was mostly observed in GFAP-positive astrocytes whereas Galectin-3 expression was observed mostly in Iba1-positive microglia/macrophages as well as CD16/32 (M1 microglial/macrophage marker)-positive cells. Moreover, genetic studies revealed a negative regulatory role of both Galectin-1 and Galectin-3 in the release of a proinflammatory cytokine, IL-6 from RAW 264.7 cells depending on the stimulus. Altogether, the present manuscript demonstrates for the first time, increased expression as well as cellular localization of Galectin-1 and Galectin-3 in the perihematomal brain regions after ICH. In addition, the manuscript raises the potential of Galectin-1 and Galectin-3 in modulating glial responses and thereby brain injury after ICH, warranting further investigation.
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