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Intracerebral hemorrhage has the characteristics of high morbidity, disability and mortality, which has caused a heavy burden to families and society. Microglia are resident immune cells in the central nervous system, and their activation plays a dual role in tissue damage after intracerebral hemorrhage. The damage in cerebral hemorrhage is embodied in the following aspects: releasing inflammatory factors and inflammatory mediators, triggering programmed cell death, producing glutamate induced excitotoxicity, and destroying blood-brain barrier; The protective effect is reflected in the phagocytosis and clearance of harmful substances by microglia, and the secretion of anti-inflammatory and neurotrophic factors. This article summarizes the function of microglia and its dual regulatory mechanism in intracerebral hemorrhage. In the future, drugs, acupuncture and other clinical treatments can be used to intervene in the activation state of microglia, so as to reduce the harm of microglia., Competing Interests: Declaration of Competing Interest The authors have nothing to declare and have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) is a serious medical problem, and promising strategy is limited. Macrophage initiated brain inflammatory injury following ICH, but the molecular mechanism had not been well identified. E3 ligase Nedd4L is implicated in the pathogenesis of the inflammatory immune response., Methods: In the present study, we detected the levels of Nedd4L in macrophages following ICH. Furthermore, Macrophage M1 polarization, pro-inflammatory cytokine production, BBB disruption, brain water content and neurological function were examined in ICH mice., Results: Here, we demonstrated that E3 ligase Nedd4L levels of macrophage increased following ICH, promoted M1 polarization inflammation by TRAF3. Nedd4L promoted BBB disruption, as well as neurological deficits. Inhibition of Nedd4L significantly attenuated M1 polarization in vivo. Inhibition of Nedd4L decreased TRAF3 and TBK1 levels, and subsequent phosphorylation of p38 and NF-κB p65 subunit following ICH., Conclusions: Our data demonstrated that Nedd4L was involved in the pathogenesis of ICH, which promoted inflammatory responses and exacerbated brain damage by TRAF3 following ICH., Competing Interests: Declaration of Competing Interest None of the authors has any conflicts of interests, and agree to submit the manuscript., (Copyright © 2023. Published by Elsevier B.V.)

T lymphocytes migrate into the brain after intracerebral hemorrhage (ICH) and promote cerebral inflammation, thus exacerbating neuronal injury. However, the relationship between of T lymphocytes infiltration and blood-brain barrier (BBB) injury after ICH has not been clarified. In this study, we investigated the spatial-temporal distribution of infiltrating T lymphocytes after ICH in C57BL/6 mice by immunofluorescence and flow cytometry, and the accompanying change rules of BBB permeability were detected by Evans blue dye leakage and tight junction protein expression. Furthermore, T lymphocyte-deficient nude mice and T lymphocyte-decreased C57BL/6 mice treated with fingolimod were used to verify the relationship between T lymphocytes infiltration and BBB leakage after ICH. Here, we reported that brain-infiltrating T lymphocytes in the hemorrhagic hemisphere began to accumulate on the first day and peaked on the fifth day after ICH; BBB leakage also at peaked on the fifth day. Moreover, T lymphocyte-deficient nude mice showed minor BBB leakage after ICH compared with C57BL/6 control mice. Similarly, fingolimod treatment can significantly decrease T lymphocyte infiltration and promote BBB integrity compared with a vehicle control. Overall, our results suggested that suppression of T lymphocyte infiltration may be a novel way to improve BBB integrity after ICH., (Copyright © 2017. Published by Elsevier B.V.)

Much evidence demonstrates that microglia mediated neuroinflammation is an important contributor to the inflammatory injury in intracerebral hemorrhage (ICH). Therefore, the compounds that can inhibit neuroinflammation are greatly needed. In the current study, we examined whether curcumin, present in a Chinese medicinal plant, could prevent ICH induced microglia activation and confer protection against neurotoxicity. The cytokines of microglia were measured by ELISA, p38MAPK/PKC and NF-κB were measured by Western blot and EMSA. Microglial toxicity was assessed using MTT and FACS assays. And neurological function was evaluated by animal behavioristics. We found that curcumin prevented ICH-induced inflammatory molecules through NF-κB activation via the p38MAPK/PKC pathway in vitro. In addition, curcumin protected hippocampal HT22 cells from indirect toxicity mediated by ICH-treated microglia cells. Further, curcumin also attenuated ICH-induced neurological deficit and cerebral water content in vivo. Together, our findings suggest that curcumin could suppress ICH induced inflammatory injury and represent a novel herbal sources for ICH therapeutical strategy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Periventricular germinal matrix hemorrhage is a devastating complication of preterm birth. Inflammation appears to play a role in brain damage after premature birth and hypoxia. The effects of rat blood plasma and serum on cytokine expression by cultured rat microglial cells were investigated. We analyzed mRNA expression levels of tumor necrosis factor (TNF)-alpha, interleukin-6 and protease activated receptor-1 and -4 by quantitative RT-PCR. Protein expression for TNFalpha was done using immunocytochemistry and ELISPOT assays. Plasma and serum had dose dependent toxic effects on microglia as measured by lactate dehydrogenase release assay and activated caspase-3 immunocytochemistry. High concentrations of plasma enhanced TNFalpha mRNA expression and protein production, while high concentrations of serum enhanced IL-6 mRNA expression. This study suggests that soluble components of blood might be differentially responsible for up regulating production of the cytokines TNFalpha and IL-6 by microglia from immature rodent brain.

There are no effective treatments for intracerebral hemorrhage (ICH). Although inflammation is a potential therapeutic target, there is a dearth of information about time-dependent and cell-specific changes in the expression of inflammation-related genes. Using the collagenase-induced ICH model in rats and real-time quantitative RT-PCR we monitored mRNA levels of markers of glial activation, pro- and anti-inflammatory cytokines, enzymes responsible for cytokine activation and several matrix metalloproteases at 6 h and 1, 3 and 7 days after ICH onset. For the most highly up-regulated genes, immunohistochemistry was then used to identify cell-specific protein expression. Finally, minocycline, a drug widely reported to reduce damage in several models of brain injury, was used to test the hypothesis that it can reduce up-regulation of inflammation-related genes when administered using a clinically relevant dosing regime: intraperitoneal injection beginning 6 h after ICH. Our results show a complex inflammatory response, with different brain cell types producing several pro- and anti-inflammatory molecules for at least 7 days after ICH onset. Included is the first demonstration that astrocytes are an important source of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6) and MMP-12. Importantly, our results demonstrate that while delayed minocycline treatment effectively reduces early up-regulation of TNFalpha and MMP-12, its efficacy is lost when treatment is extended for up to a week, and it does not reduce several other genes associated with microglia activation. These results suggest caution in extrapolating to ICH the promising results of minocycline treatment in other models of brain injury.

Previous studies on intracerebral hemorrhage (ICH) indicate that brain edema increases progressively in the first 24 h and remains elevated for several days. The cause of secondary brain injury and edema formation is uncertain. We hypothesized that inflammatory mediators released from the blood after cerebral hemorrhage might cause secondary brain injury and edema formation. This study investigates if, when and where inflammation occurs after ICH in rat. Immunocytochemistry for polymorphonuclear leukocyte marker (myeloperoxidase, MPO), microglia marker (OX42) and intracellular adhesion molecule-1 (ICAM-1) was performed in control, and 1, 3, 7 and 10 days after the injection of 100 microliter autologous blood in the right basal ganglia. Double labeling immunohistochemistry was used to identify ICAM-1 positive cells. The results show that an inflammatory response occurred in and around the blood clot after ICH, characterized by the infiltration of neutrophils and macrophages as well as activation of microglia. ICAM-1 immunoreactivity was observed in blood vessels adjacent to the clot, as well as in activated microglia and neurons in the ipsilateral hemisphere. The present study demonstrates there is an inflammatory response in the brain after ICH. Infiltrating leukocytes and activated microglia may release cytotoxic mediators contributing to secondary brain injury.