Colchicine in patients with acute ischaemic stroke or transient ischaemic attack (CHANCE-3): multicentre, double blind, randomised, placebo controlled trial.

Objectives: To assess the efficacy and safety of colchicine versus placebo on reducing the risk of subsequent stroke after high risk non-cardioembolic ischaemic stroke or transient ischaemic attack within the first three months of symptom onset (CHANCE-3).

Design: Multicentre, double blind, randomised, placebo controlled trial.

Setting: 244 hospitals in China between 11 August 2022 and 13 April 2023.

Potential Protein Signatures for Recurrence Prediction of Ischemic Stroke.

Background: Acute ischemic stroke is a major cause of mortality and disability worldwide, with approximately 7.4% to 7.7% recurrence within the first 3 months.

APOE from patient-derived astrocytic extracellular vesicles alleviates neuromyelitis optica spectrum disorder in a mouse model.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune astrocytopathy of the central nervous system, mediated by antibodies against aquaporin-4 water channel protein (AQP4-Abs), resulting in damage of astrocytes with subsequent demyelination and axonal damage. Extracellular communication through astrocyte-derived extracellular vesicles (ADEVs) has received growing interest in association with astrocytopathies. However, to what extent ADEVs contribute to NMOSD pathogenesis remains unclear.

Plasma Reference Ranges for Brain Injury Biomarkers (NfL, NfH, MCP-1, and MMP-9) in Healthy Chinese.

Background: Brain injury triggers neuroaxonal injury and neural death, that leads to the development of secondary sequelae. Throughout this process, brain injury factors released into circulation via the injured neurovascular unit are important prognostic parameters. Plasma NfL, NfH, MCP-1, and MMP-9 have been identified as potential indicators in this regard.

CD4 T cells aggravate hemorrhagic brain injury.

Leukocyte infiltration accelerates brain injury following intracerebral hemorrhage (ICH). Yet, the involvement of T lymphocytes in this process has not been fully elucidated. Here, we report that CD4 T cells accumulate in the perihematomal regions in the brains of patients with ICH and ICH mouse models.

Group 2 innate lymphoid cells resolve neuroinflammation following cerebral ischaemia.

Background: Acute brain ischaemia elicits pronounced inflammation, which aggravates neural injury. However, the mechanisms governing the resolution of acute neuroinflammation remain poorly understood. In contrast to regulatory T and B cells, group 2 innate lymphoid cells (ILC2s) are immunoregulatory cells that can be swiftly mobilised without antigen presentation; whether and how these ILC2s participate in central nervous system inflammation following brain ischaemia is still unknown.

Targeting CCL5 signaling attenuates neuroinflammation after seizure.

Background: Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates that neuroinflammation exacerbates seizure activity.

Methods: We investigated the transcriptional changes occurring in specific brain domains of a seizure mouse model, using 10× Genomics spatial transcriptomics.

Brain-derived programmed death-ligand 1 mediates immunosuppression post intracerebral hemorrhage.

Immunosuppression commonly occurs after a stroke, which is believed to be associated with the increased risk of infectious comorbidities of stroke patients, while the mechanisms underlying post-stroke immunosuppression is yet to be elucidated. In the brains of intracerebral hemorrhage (ICH) patients and murine ICH models, we identified that neuron-derived programmed death-ligand 1 (PD-L1) is reduced in the perihematomal area, associating increased soluble PD-L1 level in the peripheral blood. ICH induced a significant decrease of T and natural killer (NK) cell numbers in the periphery with an upregulation of programed death-1 (PD-1) in these cells.

Role of Immune and Inflammatory Mechanisms in Stroke: A Review of Current Advances.

Stroke accounts for a large proportion of morbidity and mortality burden in China. Moreover, there is a high prevalence of the leading risk factors for stroke, including hypertension and smoking. Understanding the underlying mechanisms and developing effective therapeutic interventions for patients with stroke is a key imperative.

Pertussis toxin-induced inflammatory response exacerbates intracerebral haemorrhage and ischaemic stroke in mice.

Background: Stroke is a devastating disease, including intracerebral haemorrhage (ICH) and ischaemic stroke. Emerging evidences indicate that systemic inflammatory cascades after stroke contribute to brain damage. However, the direct effects and features of systemic inflammation on brain injury, especially comparing between ischaemic and haemorrhagic stroke, are still obscure.

miR-1224 contributes to ischemic stroke-mediated natural killer cell dysfunction by targeting Sp1 signaling.

Background: Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke.

Methods: Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion.

Neuroblast senescence in the aged brain augments natural killer cell cytotoxicity leading to impaired neurogenesis and cognition.

Normal aging is accompanied by escalating systemic inflammation. Yet the potential impact of immune homeostasis on neurogenesis and cognitive decline during brain aging have not been previously addressed. Here we report that natural killer (NK) cells of the innate immune system reside in the dentate gyrus neurogenic niche of aged brains in humans and mice.

Cellular and molecular imaging for stem cell tracking in neurological diseases.

Stem cells (SCs) are cells with strong proliferation ability, multilineage differentiation potential and self-renewal capacity. SC transplantation represents an important therapeutic advancement for the treatment strategy of neurological diseases, both in the preclinical experimental and clinical settings. Innovative and breakthrough SC labelling and tracking technologies are widely used to monitor the distribution and viability of transplanted cells non-invasively and longitudinally.

Colivelin Rescues Ischemic Neuron and Axons Involving JAK/STAT3 Signaling Pathway.

Colivelin is a neuroprotective humanin family peptide with potent long-term capacity against Aβ deposition, neuronal apoptosis, and synaptic plasticity deficits in neurodegenerative disease. We seek to investigate whether this effect of Colivelin also govern ischemic brain injury, and potential mechanism underlying the Colivelin-mediated action on ischemic neurons. We adopted 60 min induction of transient focal cerebral ischemia and reperfusion in mice.

Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

Background And Purpose: Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury.

Activation of JAK/STAT3 restores NK-cell function and improves immune defense after brain ischemia.

Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ.

Infiltration and persistence of lymphocytes during late-stage cerebral ischemia in middle cerebral artery occlusion and photothrombotic stroke models.

Background: Evidence suggests that brain infiltration of lymphocytes contributes to acute neural injury after cerebral ischemia. However, the spatio-temporal dynamics of brain-infiltrating lymphocytes during the late stage after cerebral ischemia remains unclear.

Methods: C57BL/6 (B6) mice were subjected to sham, photothrombosis, or 60-min transient middle cerebral artery occlusion (MCAO) procedures.

A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury.

Background: Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions.

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages.

The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. The capacity for acetylcholine synthesis by NK cells increased markedly under inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), in which ChAT expression escalated along with the maturation of NK cells.

Brain Ischemia Suppresses Immunity in the Periphery and Brain via Different Neurogenic Innervations.

Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery.

Depletion of microglia exacerbates postischemic inflammation and brain injury.

Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction.