Dysregulation of Serum MicroRNA after Intracerebral Hemorrhage in Aged Mice.

Stroke is one of the most common diseases that leads to brain injury and mortality in patients, and intracerebral hemorrhage (ICH) is the most devastating subtype of stroke. Though the prevalence of ICH increases with aging, the effect of aging on the pathophysiology of ICH remains largely understudied. Moreover, there is no effective treatment for ICH. Recent studies have demonstrated the potential of circulating microRNAs as non-invasive diagnostic and prognostic biomarkers in various pathological conditions. While many studies have identified microRNAs that play roles in the pathophysiology of brain injury, few demonstrated their functions and roles after ICH. Given this significant knowledge gap, the present study aims to identify microRNAs that could serve as potential biomarkers of ICH in the elderly. To this end, sham or ICH was induced in aged C57BL/6 mice (18-24 months), and 24 h post-ICH, serum microRNAs were isolated, and expressions were analyzed. We identified 28 significantly dysregulated microRNAs between ICH and sham groups, suggesting their potential to serve as blood biomarkers of acute ICH. Among those microRNAs, based on the current literature, miR-124-3p, miR-137-5p, miR-138-5p, miR-219a-2-3p, miR-135a-5p, miR-541-5p, and miR-770-3p may serve as the most promising blood biomarker candidates of ICH, warranting further investigation.

Intracerebral Hemorrhage: The Effects of Aging on Brain Injury.

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke with high rates of mortality and morbidity. ICH patients often suffer devastating and debilitating neurological impairments, from which the majority of victims are unable to fully recover to functional independence. Unfortunately, there is no established medical therapy for ICH, which is partly attributed to the lack of understanding of the complex pathology of the disorder. Despite advanced age being a major risk factor of ICH, most preclinical studies on ICH employed young animal subjects. Due to this discrepancy, the molecular level changes in the aging brain after ICH are largely unknown, limiting the translation of preclinical studies into potential human treatments. The purpose of this review is to highlight the effects of advanced age on ICH- induced brain injury and recovery and to draw attention to current knowledge gaps, which warrant further investigation.

High glucose removes natural anti-α-galactoside and anti-ß-glucoside antibody immune complexes adhering to surface O-glycoproteins of normal platelets and enhances platelet aggregation.

Human natural anti-α-galactoside (anti-Gal) and anti-ß-glucoside (ABG) antibodies were previously reported to recognize the serine- and threonine-rich peptide sequences (STPS) of albumin-associated O-glycoproteins (AOP1 and AOP2) as surrogate antigens, forming anti-Gal/ABG-AOP1/AOP2-albumin triplet immune complexes in plasma. Since antibodies in these triplets still possessed unoccupied binding sites, the presence of triplets on human platelets that abound in surface O-glycoproteins was examined. Upon treatment with α-galactosides and ß-glucosides, normal platelets freshly isolated from young healthy individuals released triplets identical with plasma triplets according to ELISA results. The resulting denuded platelets, unless pre-treated with fibrinogen or the O-glycan-binding lectin jacalin, recaptured these sugar-extracted triplets in the absence of antibody-specific sugars, suggesting that the triplet antibodies recognized the STPS of O-glycosylated receptors on platelets. Molecular weight of the dominant jacalin-binding subunit on triplet-free platelet membrane was 116 kDa, close to the ~120 kDa reported for the IIb subunit of the most abundant fibrinogen-binding platelet O-glycoprotein, GPIIb/IIIa. Denuded, but not native, platelets underwent slow spontaneous aggregation and rapid ADP-mediated GPIIb/IIIa-dependent aggregation according to spectrophotometric assay. Pre-treatment of denuded platelets with jacalin significantly reduced their ADP-mediated aggregation. Amyloid ß (Aß-42 monomer) was reported to bind triplet O-glycoproteins through their STPS but not to albumin or the antibodies. This peptide bound to the triplets on normal platelets and to surface membrane O-glycoproteins on denuded platelets, suggesting that the surface O-glycoproteins on the normal platelets were engaged and masked by the triplets. The ABG-specific sugar glucose denuded the platelets at concentrations typically reached in diabetic sera, since anti-Gal specific or ABG-specific sugar released the triplets of both the antibodies from the platelets. In conclusion, the present study offered rationale for the presence of anti-Gal/ABG-O-glycoprotein-albumin triplets on normal platelets, for the role of triplets in platelet physiology amidst circulating platelet-activating factors such as ADP, and for platelet vulnerability during diabetes.

Dysregulation of microRNA and Intracerebral Hemorrhage: Roles in Neuroinflammation.

Intracerebral hemorrhage (ICH) is a major public health problem and devastating subtype of stroke with high morbidity and mortality. Notably, there is no effective treatment for ICH. Neuroinflammation, a pathological hallmark of ICH, contributes to both brain injury and repair and hence, it is regarded as a potential target for therapeutic intervention. Recent studies document that microRNAs, small non-coding RNA molecules, can regulate inflammatory brain response after ICH and are viable molecular targets to alter brain function. Therefore, there is an escalating interest in studying the role of microRNAs in the pathophysiology of ICH. Herein, we provide, for the first time, an overview of the microRNAs that play roles in ICH-induced neuroinflammation and identify the critical knowledge gap in the field, as it would help design future studies.

Entinostat improves acute neurological outcomes and attenuates hematoma volume after Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) or hemorrhagic stroke is a major public health problem with no effective treatment. Given the emerging role of epigenetic mechanisms in the pathophysiology of ICH, we tested the hypothesis that a class 1 histone deacetylase inhibitor (HDACi), Entinostat, attenuates neurodegeneration and improves neurobehavioral outcomes after ICH. To address this, we employed a preclinical mouse model of ICH and Entinostat was administered intraperitoneally one-hour post induction of ICH. Entinostat treatment significantly reduced the number of degenerating neurons and TUNEL-positive cells after ICH in comparison to vehicle-treated controls. Moreover, Entinostat treatment significantly reduced hematoma volume, T2-weighted hemorrhagic lesion volume and improved acute neurological outcomes after ICH. Further, Entinostat significantly reduced the hemin-induced release of proinflammatory cytokines in vitro. Consistently, the expression of proinflammatory microglial/macrophage marker, CD16/32, was remarkably reduced in Entinostat treated group after ICH in comparison to control. Altogether, data implicates the potential of class 1 HDACi, Entinostat, in improving acute neurological function after ICH warranting further investigation.

Brain injury and repair after intracerebral hemorrhage: The role of microglia and brain-infiltrating macrophages.

Intracerebral hemorrhage (ICH) is a major public health problem characterized by cerebral bleeding. Despite recent advances in preclinical studies, there is no effective treatment for ICH making it the deadliest subtype of stroke. The lack of effective treatment options partly attributes to the complexity as well as poorly defined pathophysiology of ICH. The emerging evidence indicates the potential of targeting secondary brain damage and hematoma resolution for improving neurological outcomes after ICH. Herein, we provide an overview of our understanding of the functional roles of activated microglia and brain-infiltrating monocyte-derived macrophages in brain injury and repair after ICH. The clinical and preclinical aspects that we discuss in this manuscript are related to ICH that occurs in adults, but not in infants. Also, we attempt to identify the knowledge gap in the field for future functional studies given the potential of targeting microglia and brain-infiltrating macrophages for therapeutic intervention after ICH.

A Combined Proteomics and Bioinformatics Approach Reveals Novel Signaling Pathways and Molecular Targets After Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a non-traumatic cerebrovascular disorder with very high morbidity and mortality and regarded as one of the deadliest stroke subtypes. Notably, there is no effective treatment for ICH. Despite an overall increase in preclinical studies, the pathophysiology of ICH is complex and remains enigmatic. To this end, ICH was induced in male CD-1 mice and the ipsilateral brain tissue was characterized in an unbiased manner using a combination of proteomics and bioinformatics approaches. A total of 4833 proteins were revealed by quantitative proteomic analysis. Of those, 207 proteins exhibited significantly altered expression after ICH in comparison to sham. It was found that 46 proteins were significantly upregulated and 161 proteins were significantly downregulated after ICH compared to sham. The quantitative proteomics approach combined with bioinformatics revealed several novel molecular targets (cyclin-dependent-like kinase 5, E3 ubiquitin-protein ligase, protein phosphatase 2A-alpha, protein phosphatase 2A-beta, serine/threonine-protein kinase PAK1, alpha-actinin-4, calpain-8, axin-1, NCK1, and septin-4), and related signaling pathways, which could play roles in secondary brain injury and long-term neurobehavioral outcomes after ICH warranting further investigation.

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.

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.

[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.

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-1ß after ICH. Altogether, the data suggest the efficacy of post-injury administration of Resveratrol in improving acute neurological function after ICH.

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

BACKGROUND: Intracerebral 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. METHODS: In 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. RESULTS: The 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. CONCLUSIONS: Altogether, 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.

Post-Injury Administration of Tert-butylhydroquinone Attenuates Acute Neurological Injury After Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a severe form of stroke with substantial public health impact. Notably, there is no effective treatment for ICH. Given the role of transcription factor Nrf2 (NF-E2-related factor 2) in antioxidant signaling, herein, we tested the efficacy of tert-butylhydroquinone (TBHQ), a selective inducer of Nrf2 in a preclinical model of ICH. Male CD1 mice were subjected to experimental intracerebral hemorrhage and administered intraperitoneally with TBHQ. The administration of TBHQ enhanced the DNA-binding activity of Nrf2 in the brain and reduced oxidative brain damage in comparison to vehicle-treated ICH. In addition, TBHQ treatment reduced microglial activation with concomitant reduction in the release of proinflammatory cytokine interleukin-1ß (IL-1 ß). Furthermore, TBHQ treatment attenuated neurodegeneration and improved neurological outcomes after ICH. Altogether, the data demonstrate the efficacy of post-injury administration of TBHQ in attenuating acute neurological injury after ICH.

The Histone Deacetylase Inhibitor Suberoylanilide Hydroxamic Acid (SAHA) Confers Acute Neuroprotection After Intracerebral Hemorrhage in Mice.

Spontaneous intracerebral hemorrhage (ICH) is a stroke subtype with no effective treatment. Though ICH is known to induce severe neurological damage, the molecular mechanisms of neurological injury after ICH remain largely unclear. Given the emerging role of epigenetic mechanisms in neurodegeneration, the present study evaluated whether suberoylanilide hydroxamic acid (SAHA: vorinostat), a clinically well-tolerated pan-histone deacetylase inhibitor (HDACi), would attenuate neurological injury and improve functional outcomes in a preclinical model of ICH. Mice were administered with SAHA or vehicle after an induction of ICH and acute neuronal death, glial activation, and neurological outcomes were assessed. SAHA-treated mice exhibited less neurodegeneration with concomitant improvement in neurological outcomes than vehicle-treated mice. Furthermore, SAHA downregulated glial activation and the expression of heme oxygenase-1, a stress-inducible enzyme that plays critical roles in neurological damage after ICH. Altogether, the data strongly suggest the role of epigenetic mechanisms in inducing neurological injury after ICH and raise the possible clinical utility of SAHA for therapeutic intervention after ICH.

Overexpression of Nrf2 attenuates Carmustine-induced cytotoxicity in U87MG human glioma cells.

BACKGROUND: Malignant glioma is one of the most devastating tumors in adults with poor patient prognosis. Notably, glioma often exhibits resistance to conventional chemotherapeutic approaches, complicating patient treatments. However, the molecular mediators involved in tumor chemoresistance remain poorly defined, creating a barrier to the successful management of glioma. In the present study, we hypothesized that the antioxidant transcription factor, Nrf2 (nuclear factor erythroid-derived 2 like 2), attenuates glioma cytotoxicity to Carmustine (BCNU), a widely used chemotherapeutic agent known to modulate cellular oxidative balance. METHODS: To test the hypothesis, we employed human malignant glioma cell line, U87MG and overexpression of Nrf2 in glioma cells was achieved using both pharmacological and genetic approaches. RESULTS: Notably, induction of Nrf2 was associated with increased expression of heme oxygenase-1 (HO-1), a stress inducible enzyme involved in anti-oxidant defense. In addition, over expression of Nrf2 in U87MG cells significantly attenuated the cytotoxicity of Carmustine as evidenced by both cellular viability assay and flow cytometry analysis. Consistent with this, antioxidants such as glutathione and N-acetyl cysteine significantly reduced Carmustine mediated glioma cytotoxicity. CONCLUSIONS: Taken together, these data strongly implicate an unexplored role of Nrf2 in glioma resistance to Carmustine and raise the possible use of Nrf2 inhibitors as adjunct to Carmustine for the treatment of malignant glioma.

Activation of the endothelin system mediates pathological angiogenesis during ischemic retinopathy.

Retinopathy of prematurity adversely affects premature infants because of oxygen-induced damage of the immature retinal vasculature, resulting in pathological neovascularization (NV). Our pilot studies using the mouse model of oxygen-induced retinopathy (OIR) showed marked increases in angiogenic mediators, including endothelins and endothelin receptor (EDNR) A. We hypothesized that activation of the endothelin system via EDNRA plays a causal role in pathological angiogenesis and up-regulation of angiogenic mediators, including vascular endothelial growth factor A (VEGFA) in OIR. Mice were exposed to 75% oxygen from post-natal day P7 to P12, treated with either vehicle or EDNRA antagonist BQ-123 or EDNRB antagonist BQ-788 on P12, and kept at room air from P12 to P17 (ischemic phase). RT-PCR analysis revealed increased levels of EDN2 and EDNRA mRNA, and Western blot analysis revealed increased EDN2 expression during the ischemic phase. EDNRA inhibition significantly increased vessel sprouting, resulting in enhanced physiological angiogenesis and decreased pathological NV, whereas EDNRB inhibition modestly improved vascular repair. OIR triggered significant increases in VEGFA protein and mRNA for delta-like ligand 4, apelin, angiopoietin-2, and monocyte chemoattractant protein-1. BQ-123 treatment significantly reduced these alterations. EDN2 expression was localized to retinal glia and pathological NV tufts of the OIR retinas. EDN2 also induced VEGFA protein expression in cultured astrocytes. In conclusion, inhibition of the EDNRA during OIR suppresses pathological NV and promotes physiological angiogenesis.

High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI.

Astrocyte-specific expression of survivin after intracerebral hemorrhage in mice: a possible role in reactive gliosis?

Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, accounts for up to 15% of all strokes. Despite maximal surgical intervention and supportive care, ICH is associated with significant morbidity and mortality, in part due to a lack of viable treatment options. Astrogliosis, a key feature of secondary injury that is characterized by glial proliferation, is a poorly-defined process that may produce both beneficial and detrimental outcomes after brain injury. Using a pre-clinical murine model of collagenase-induced ICH, we demonstrate a delayed upregulation of survivin, a key molecule involved in tumor cell proliferation and survival, by 72 h post-ICH. Notably, this increase in survivin expression was prominent in GFAP-positive astrocytes, but absent in neurons. Survivin was not expressed at detectable levels in the striatum of sham-operated mice. The expression of survivin after ICH was temporally and spatially associated with the expression of proliferating cell nuclear antigen (PCNA), an established marker of cellular proliferation. Moreover, the survivin expression was co-localized in proliferating astrocytes as evidenced by triple-label immunohistochemistry. Finally, shRNA-mediated silencing of survivin expression attenuated PCNA expression and reduced cellular proliferation in human glial cells. Together, these data suggest a potentially novel role for survivin in functionally promoting astrocytic proliferation after ICH.

Astrogliosis: a target for intervention in intracerebral hemorrhage?

Intracerebral hemorrhage (ICH) is a debilitating neurological injury, accounting for 10-15 % of all strokes. Despite neurosurgical intervention and supportive care, the 30-day mortality rate remains ~50 %, with ICH survivors frequently displaying neurological impairments and requiring long-term assisted care. Unfortunately, the lack of medical interventions to improve clinical outcomes has led to the notion that ICH is the least treatable form of stroke. Hence, additional studies are warranted to better understand the pathophysiology of ICH. Astrogliosis is an underlying astrocytic response to a wide range of brain injuries and postulated to have both beneficial and detrimental effects. However, the molecular mechanisms and functional roles of astrogliosis remain least characterized following ICH. Herein, we review the functional roles of astrogliosis in brain injuries and raise the prospects of therapeutically targeting astrogliosis after ICH.