Differential Cellular Expression of Galectin-1 and Galectin-3 After Intracerebral Hemorrhage

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-post-injury, 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

TSPO: An Evolutionarily Conserved Protein with Elusive Functions

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

Resveratrol Attenuates Neurodegeneration and Improves Neurological Outcomes after Intracerebral Hemorrhage in Mice

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: Blood Components and Neurotoxicity

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

[125 I]IodoDPA-713 Binding to 18 kDa Translocator Protein (TSPO) in a Mouse Model of Intracerebral Hemorrhage: Implications for Neuroimaging

Intracerebral hemorrhage (ICH) is a fatal stroke subtype with significant public health impact. Although neuroinflammation is a leading cause of neurological deficits after ICH, no imaging tool is currently available to monitor brain inflammation in ICH patients. Given the role of TSPO in neuroinflammation, herein we investigate whether a second-generation TSPO ligand, [125 I]IodoDPA-713 can be used to monitor the changes in TSPO expression in a preclinical model of intracerebral hemorrhage. Male CD1 mice were subjected to ICH/Sham. The brain sections, collected at different time points were incubated with [125 I]IodoDPA-713 and the brain uptake of [125 I]IodoDPA-713 was estimated using autoradiography. The specificity of [125 I]IodoDPA-713 binding was confirmed by a competitive displacement study with an unlabeled TSPO ligand, PK11195. [125 I]IodoDPA-713 binding was higher in the ipsilateral striatum with an enhanced binding observed in the peri-hematomal brain region after ICH, whereas the brain sections from sham as well as contralateral brain areas of ICH exhibited marginal binding of [125 I]IodoDPA-713. PK11195 completely reversed the [125 I] IodoDPA-713 binding to brain sections suggesting a specific TSPO-dependent binding of [125 I]IodoDPA-713 after ICH. This was further confirmed with immunohistochemistry analysis of adjacent sections, which revealed a remarkable expression of TSPO in the areas of high [125 I]IodoDPA-713 binding after ICH. The specific as well as enhanced binding of [125 I]IodoDPA-713 to the ipsilateral brain areas after ICH as assessed by autoradiography analysis provides a strong rationale for testing the applicability of [125 I]IodoDPA-713 for non-invasive neuroimaging in preclinical models of ICH