BackgroundBow Hunter's Syndrome (BHS) is a rare condition in which dynamic vertebral artery (VA) compression during neck rotation induces transient symptoms, such as vertigo, whereas major arterial occlusion is extremely uncommon. There is no standardized treatment for BHS, and management includes conservative, surgical, and rarely endovascular approaches. We report a unique case of BHS with acute VA occlusion successfully treated by mechanical thrombectomy followed by elective stent placement.Case ReportAn 87-year-old woman presented with right gaze deviation, dysarthria, right hemiparesis, and sensory disturbance. Magnetic resonance imaging showed acute infarcts in the left pons and cerebellum, while magnetic resonance angiography showed poor visualization from the VA to the basilar artery. Emergency cerebral angiography showed VA occlusion, and subsequent thrombectomy was performed, which resulted in successful recanalization. Post-recanalization angiography showed residual stenosis at the V3 segment and an anomalous course of the VA running caudal to the posterior arch of the atlas. A dynamic ultrasonographic examination with neck rotation showed occlusion of the VA, which confirmed the diagnosis of BHS. Stent placement was planned because compression of the left VA was confirmed to be caused by soft tissue rather than by bony structures. Balloon angioplasty showed resistance to external compression. Subsequently, a balloon-expandable stent was successfully deployed using a distal access catheter and a stiff micro guidewire. Follow-up imaging confirmed VA patency with preserved flow during head rotation. The patient showed neurological improvement without recurrence during 6 months of follow-up.ConclusionWe report a rare case of BHS presenting with acute VA occlusion treated effectively with endovascular therapy. BHS should be considered as a potential cause of large-vessel occlusion in posterior circulation stroke when abnormal arterial courses are identified. In selected cases, stent placement may be a feasible therapeutic option depending on the compressive structure.

Zebra bodies-electron-dense lamellar lysosomal inclusions-are the renal hallmark of Fabry disease, caused by deficient α-galactosidase A (GLA) activity. However, several pharmacological agents with cationic amphiphilic properties produce morphologically indistinguishable deposits, resulting in drug-induced phospholipidosis. We describe a woman in her 50s referred to nephrology with non-nephrotic proteinuria and non-visible haematuria following an ischaemic stroke treated with prednisolone and methotrexate for concomitant medium-vessel vasculitis. Aetiological workup-including autoimmunity, anti-phospholipase A2 receptor and GLA gene sequencing-was negative. Renal biopsy revealed lamellated myelin bodies in podocyte cytoplasm on electron microscopy, alongside thin basement membrane disease. Given negative Fabry testing and chronic sertraline exposure-a selective serotonin reuptake inhibitor with known cationic amphiphilic properties-the drug was discontinued. Proteinuria fell from 2.8 g/24 hours to 0.13 g/24 hours at 6 months, with complete resolution of non-visible haematuria. This case underscores the importance of pharmacological review in Zebra body nephropathy.

Fewer than half of patients receive evidence-based upper limb rehabilitation after stroke. Implementation science interventions may improve use of guidelines by clinicians; however, it is not yet known whether they lead to evidence-based stroke rehabilitation practice. We aim to determine the effect and cost-effectiveness of a champion-led implementation package (PROMOTE) to increase adherence to best practice guidelines for upper limb rehabilitation after stroke.

Ischemic stroke induced cerebral edema is a devastating complication which leads to excessive swelling, increased intracranial pressure (ICP) and rapid neurological deterioration. The mortality rate of post-stroke cerebral edema is approximately 80 %. However, therapeutic options for post-stroke cerebral edema are sparce, emphasizing an urgent need to explore new therapeutic strategies for post-stroke edema. In past few decades stem cell therapy has been a promising therapeutic strategy in decreasing infarct volume and promoting functional recovery by various mechanisms following stroke. Previous studies from our lab demonstrated that IA-MSCs administration were beneficial in mitigating post-stroke edema by regulating PKCδ/ MMP9/AQP4 axis and promoting blood-brain-barrier (BBB) integrity. It has also been reported that IA-MSCs administration mitigate post-stroke edema by maintaining BBB integrity, mitochondria function and regulating AQP4 expression by modulation of the SIRT-1/PKCδ/NF-κB axis. In this chapter, we illustrated a multi-level methodological approach to assess therapeutic outcomes of IA-MSCs in alleviating post-stroke cerebral edema by utilizing behavioural analyses, histological staining, biochemical assays, mitochondrial functional assays and molecular investigations by RT-PCR, western blotting and immunofluorescence staining.

Stroke is a cerebrovascular disorder characterized by focal or global cerebral tissue damage, which ranks among the leading causes of mortality and disability globally. Ischemic stroke accounts for approximately 65.3% of all stroke cases. Currently, therapeutic strategies for ischemic stroke remain suboptimal. The concept of the neurovascular unit emphasizes the integrated regulation of neural and vascular components, and neurogenesis and angiogenesis represent the core neurovascular responses during ischemic stroke recovery. These two processes exhibit intimate crosstalk, forming a neurovascular collaborative repair mechanism that is precisely regulated by multiple cytokines and key signaling pathways. This review systematically summarizes the underlying mechanisms of this crosstalk and its pivotal role in post-stroke tissue repair and neurological functional recovery. Despite significant advances in this field, current research still has notable limitations, including insufficient elucidation of the interactions among multiple factors and pathways, unclear dynamic patterns of crosstalk across different recovery stages, and a lack of correlation between preclinical animal models and clinical scenarios. Future investigations should employ advanced technologies (e.g., single-cell sequencing) to further explore crosstalk mechanisms, focus on crosstalk associated with neural cell transdifferentiation, and establish preclinical models that closely mimic clinical conditions. Targeting the crosstalk between neurogenesis and angiogenesis represents a promising preclinical approach for precise therapeutic intervention. Although current evidence is largely derived from animal models, this strategy holds potential to address some of the current clinical limitations and improve neurological functional recovery and long-term quality of life in patients with ischemic stroke, pending rigorous validation in future clinical studies.

Ischemic stroke is an unmet therapeutic need, characterised by excessive oxidative stress, mitochondrial impairment, blood-brain barrier (BBB) damage, and neuronal cell death. 4-Octyl itaconate (4-OI) is known for its promising antioxidant properties; however, its effects in cerebral ischemia/reperfusion (I/R) injury have not been previously explored. In this study, middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were used to mimic the cerebral I/R injury. Treatment with 4-OI significantly improved neuronal survival and neurological outcomes, reduced oxidative damage and mitochondrial dysfunction. Mechanistically, 4-OI markedly attenuated intracellular and mitochondrial ROS, restored mitochondrial membrane potential, and inhibited neuronal apoptosis. Furthermore, 4-OI treatment exerts its neuroprotective effect by suppressing lipid peroxidation and modulating the Nrf2/HO-1/SLC7A11/GPX4 axis to inhibit ferroptosis and BBB damage. Pharmacological inhibition of Nrf2 using ML-385 abolished the effects of 4-OI, confirming the essential role of Nrf2 activation in mediating ferroptosis suppression. Additionally, molecular docking analysis revealed favourable binding of 4-OI to Keap-1, supporting a potential mechanism by which 4-OI impede the Keap1-Nrf2 interaction to promote Nrf2 activation. Collectively, these findings suggest that 4-OI confers Neuroprotection against I/R injury by activating Nrf2 pathway, reducing oxidative stress, and suppressing ferroptotic and apoptotic cell death. This study identifies 4-OI as a promising therapeutic candidate for cerebral I/R injury and highlights the Nrf2-mediated ferroptosis pathway as a potential target for neuroprotection.

Programmed cell death protein-1 (PD-1) and its ligand PD-L1 constitute a central immune checkpoint pathway that maintains immune tolerance and limits excessive inflammation. Beyond oncology, emerging evidence indicates that PD-1/PD-L1 signaling plays fundamental roles in central and peripheral nervous system (CNS and PNS) homeostasis. In the brain, PD-1/PD- L1 restrains neuroinflammation, regulates microglial and astrocytic activation, and influences synaptic function and neurodevelopment, thereby contributing to the pathophysiology of autoimmune demyelinating disease, stroke, Alzheimer's disease, Parkinson's disease, and psychiatric disorders. Outside the brain, PD-1/PD-L1 signaling modulates nociceptive processing in sensory ganglia and the spinal cord, as well as the trafficking and function of circulating monocytes, revealing a multi-layered neuroimmune regulatory network. However, the functional impacts of PD-1/PD-L1 are highly dependent on factors like disease context, cell type, disease stage, and sex. Accordingly, we critically evaluate the therapeutic opportunities and limitations of both PD-1/PD-L1 blockade and agonism across these diverse neurological and psychiatric conditions. Due to major translational hurdles, including limited CNS drug penetration, immune-related adverse events, and the opposing outcomes of pathway modulation in different compartments or phases of disease, future strategies will likely require spatiotemporally controlled and cell-specific modulation of PD-1/PD-L1 signaling, improved central nervous system drug delivery, and biomarker-guided patient stratification. Collectively, this review integrates CNS, PNS, and systemic immune interactions to position PD-1/PD-L1 as a potential target for next-generation neuro-immunotherapies across neurological and psychiatric disorders.