Single-Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post-Stroke.

The activation and infiltration of immune cells are hallmarks of ischemic stroke. However, the precise origins and the molecular alterations of these infiltrating cells post-stroke remain poorly characterized. Here, a murine model of stroke (permanent middle cerebral artery occlusion [p-MCAO]) is utilized to profile single-cell transcriptomes of immune cells in the brain and their potential origins, including the calvarial bone marrow (CBM), femur bone marrow (FBM), and peripheral blood mononuclear cells (PBMCs).

Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke.

Background: Central nervous system (CNS) accessibility constitutes a major hurdle for drug development to treat neurological diseases. Existing drug delivery methods rely on breaking the blood-brain barrier (BBB) for drugs to penetrate the CNS. Researchers have discovered natural microchannels between the skull bone marrow and the dura mater, providing a pathway for drug delivery through the skull bone marrow.

Multicentre prospective, randomised open-label, endpoint-blinded study to evaluate the safety and efficacy of propranolol for the prevention of stroke-associated pneumonia in patients with intracerebral haemorrhage (PROCHASE): rationale and design.

Background: Stroke-induced transient immune suppression is believed to contribute to post-stroke infections. The β-adrenergic receptor antagonist, propranolol, has been shown to prevent stroke-associated pneumonia (SAP) via reversing post-stroke immunosuppression in preclinical studies and in retrospective analysis in stroke patients. However, whether propranolol can reduce the risk of SAP has not been tested in prospective, randomised controlled trials.

Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroinflammation in aged patients with traumatic brain injury.

Aged patients often suffer poorer neurological recovery than younger patients after traumatic brain injury (TBI), but the mechanisms underlying this difference remain unclear. Here, we demonstrate abnormal myelopoiesis characterized by increased neutrophil and classical monocyte output but impaired nonclassical patrolling monocyte population in aged patients with TBI as well as in an aged murine TBI model. Retrograde and anterograde nerve tracing indicated that increased adrenergic input through the central amygdaloid nucleus-bone marrow axis drives abnormal myelopoiesis after TBI in a β2-adrenergic receptor-dependent manner, which is notably enhanced in aged mice after injury.

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.

Autonomic dysfunction and treatment strategies in intracerebral hemorrhage.

Aims: Autonomic dysfunction with central autonomic network (CAN) damage occurs frequently after intracerebral hemorrhage (ICH) and contributes to a series of adverse outcomes. This review aims to provide insight and convenience for future clinical practice and research on autonomic dysfunction in ICH patients.

Discussion: We summarize the autonomic dysfunction in ICH from the aspects of potential mechanisms, clinical significance, assessment, and treatment strategies.

White matter disease derived from vascular and demyelinating origins.

Damage or microstructural alterations of the white matter can cause dysfunction of the intrinsic neural networks in a condition termed as white matter disease (WMD). Frequently detected on brain computed tomography and magnetic resonance imaging scans, WMD is commonly presented in inflammatory demyelinating diseases like multiple sclerosis (MS) and vascular diseases such as cerebral small vessel disease (CSVD). Prevention of MS and CSVD progression requires early treatments with drastically different medications and approaches, as such, early and accurate diagnosis of WMD, derived from vascular or demyelinating etiologies, is of paramount importance.

Neurovascular Inflammation and Complications of Thrombolysis Therapy in Stroke.

Intravenous thrombolysis via tPA (tissue-type plasminogen activator) is the only approved pharmacological treatment for acute ischemic stroke, but its benefits are limited by hemorrhagic transformation. Emerging evidence reveals that tPA swiftly mobilizes immune cells which extravasate into the brain parenchyma via the cerebral vasculature, augmenting neurovascular inflammation, and tissue injury. In this review, we summarize the pronounced alterations of immune cells induced by tPA in patients with stroke and experimental stroke models.

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.

Plasma Neurofilament Light Chain Predicts Mortality and Long-Term Neurological Outcomes in Patients with Intracerebral Hemorrhage.

Patients with intracerebral hemorrhage (ICH) often suffer from heterogeneous long-term neurological deficits, such as cognitive decline. Our ability to measure secondary brain injury to predict the long-term outcomes of these patients is limited. We investigated whether the blood neurofilament light chain (NfL) can monitor brain injury and predict long-term outcomes in patients with ICH.

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.

Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients.

Endothelial BACE1 Impairs Cerebral Small Vessels via Tight Junctions and eNOS.

Background: Cerebral small vessel injury, including loss of endothelial tight junctions, endothelial dysfunction, and blood-brain barrier breakdown, is an early and typical pathology for Alzheimer's disease, cerebral amyloid angiopathy, and hypertension-related cerebral small vessel disease. Whether there is a common mechanism contributing to these cerebrovascular alterations remains unclear. Studies have shown an elevation of BACE1 (β-site amyloid precursor protein cleaving enzyme 1) in cerebral vessels from cerebral amyloid angiopathy or Alzheimer's disease patients, suggesting that vascular BACE1 may involve in cerebral small vessel injury.

O-GlcNAcase inhibitor has protective effects in intracerebral hemorrhage by suppressing the inflammatory response.

Background: Intracerebral hemorrhage (ICH) is aggravated by immune cells that participate in the inflammatory response from the blood-brain barrier (BBB). O-Glycosylation has been reported to regulate the inflammatory response in the central nervous system but its cerebral protective effects remain unknown. Therefore, this study was carried out to investigate the protective effects of O-GlcNAcylation in a murine model of ICH and the possible mechanisms involved.

Brain injury instructs bone marrow cellular lineage destination to reduce neuroinflammation.

Acute brain injury mobilizes circulating leukocytes to transmigrate into the perivascular space and brain parenchyma. This process amplifies neural injury. Bone marrow hematopoiesis replenishes the exhausted peripheral leukocyte pools.

Low-dose rituximab treatment for new-onset generalized myasthenia gravis.

The aim of this retrospective case series study was to evaluate the response and durability of rituximab in patients with new-onset acetylcholine receptor positive (AChR +) generalized myasthenia gravis (MG). Patients were initiated with low-dose rituximab treatment within 3.5 months of onset without concomitant oral immunosuppressants.

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.

tPA Mobilizes Immune Cells That Exacerbate Hemorrhagic Transformation in Stroke.

Rationale: Hemorrhagic complications represent a major limitation of intravenous thrombolysis using tPA (tissue-type plasminogen activator) in patients with ischemic stroke. The expression of tPA receptors on immune cells raises the question of what effects tPA exerts on these cells and whether these effects contribute to thrombolysis-related hemorrhagic transformation.

Objective: We aim to determine the impact of tPA on immune cells and investigate the association between observed immune alteration with hemorrhagic transformation in ischemic stroke patients and in a rat model of embolic stroke.

Cortical Thinning and Ventricle Enlargement in Neuromyelitis Optica Spectrum Disorders.

In neuromyelitis optica spectrum disorders (NMOSDs), inflammation is not the sole driver of accumulation of disability; neurodegeneration is another important pathological process. We aim to explore different patterns of cortical atrophy and ventricular enlargement in NMOSD. We retrospectively analyzed a cohort of 230 subjects, comprising 55 healthy controls (HCs), 85 multiple sclerosis (MS), and 90 NMOSD patients from Tianjin Medical University General Hospital and Beijing Tiantan Hospital.