Background The molecular mechanisms governing adaptive neuroprotection during the postpartum period remain unknown. We hypothesized that circulating exosomes contain bioactive cargo (such as Hsp20) that confer neuroprotection against ischemic injury during the postpartum period. Methods Exosomes were isolated from plasma of postpartum female mice (ppExos) and control female mice, and from serial blood samples obtained from healthy human volunteers during pregnancy (3rd trimester) and again on postpartum day 2. Exosomal size and protein markers were confirmed via nanoparticle tracking analysis and Western blotting. Neuroprotection with exosome treatment was assessed in vitro using mouse neuronal and astrocyte cultures and human retinal pigment cell line subjected to simulated ischemia. I n vivo neuroprotection was assessed using transient middle cerebral artery occlusion (MCAO) in young adult and aged mice. Mitochondrial integrity and reactive oxygen species (ROS) production were evaluated by live cell imaging. In vivo neuroprotection was evaluated by assessing infarct volume and neurobehavioral scores. Changes in mitochondrial dynamics were measured by immunofluorescence and Western blot. Human exosomes were sent for proteomic assessment (SomaScan™) followed by differential expression analysis (R software v4). Protein quantification was validated by immunoblot. Results ppExos significantly reduced infarct volumes and improved neurological deficits post-MCAO in both young and aged female mice. In vitro , ppExos reduced ROS generation in all cell types after simulated ischemia and reduced mitochondrial fragmentation in astrocytes. Mitochondrial fusion proteins Mfn2 and Opa1 proteins were elevated in maternal postpartum brains, and preserved in both astrocyte and neuronal cell cultures after in vitro ischemia with ppExo treatment. Proteomics revealed significant upregulation of heat shock protein 20 (Hsp20) in human ppExos, while Western blot validated elevated Hsp20 in both human and mouse ppExos. Simulated ischemia significantly reduced Hsp20 in astrocyte and neuronal cultures which was reversed by treatment with ppExos. In conclusion, ppExos represent a previously unrecognized, naturally optimized neuroprotective agent that enhances mitochondrial resilience and antioxidant defenses associated with enhanced Hsp20 expression. These findings establish a novel platform for sex-informed, cell-free therapies in ischemic cerebrovascular accidents.

A man in his late 60s with a history of arterial hypertension, dyslipidaemia and a cerebrovascular accident 20 years ago presented to the emergency department with sudden-onset blurred vision in his right eye, accompanied by pain, dizziness, sweating and high blood pressure (160/110 mmHg). Ophthalmic examination revealed a decreased visual acuity in the right eye (less than 6/60), with best corrected visual acuity of 6/7.5. Fundoscopy showed retinal cholesterol emboli and ischaemic changes. Carotid duplex ultrasound indicated possible stenosis of the internal carotid artery. The patient was started on antiplatelet therapy with acetylsalicylic acid and 24-hour cardiac telemetry monitoring. A brain MRI performed 2 days later showed acute ischaemic infarcts in the right frontal and periventricular regions. Intracranial and cervical magnetic resonance angiography confirmed internal carotid artery occlusion with no flow in the intracranial portion.

Retinal artery occlusion (RAO), a blinding emergency, demands clarification of cellular spatiotemporal dynamics for targeted therapies. Single-cell RNA-seq is powerful but lacks spatial context, whereas spatial transcriptomics struggles with cell segmentation errors and low transcript capture efficiency. To overcome these, we developed the ASCAL (Automated Single-Cell Annotation and Localization) pipeline, integrating complementary spatial transcriptomics techniques: single-nucleus-resolution SeekSpace for cell annotation reference and uniform-coverage Stereo-seq for localization of annotated cells. This strategy enables automated annotation and localization of large-scale scRNA-seq datasets with minimal spatial sections. Leveraging ASCAL, we constructed a mouse whole-eye single-cell spatial atlas precisely mapping cell types across the ciliary body and retina. Moreover, we revealed pronounced spatial immune activation specifically enriched in the ganglion cell layer (GCL) in the RAO model, further validated by immunofluorescence staining. We also uncovered a selective depletion of active Rods. Importantly, RNAscope assays independently validated both the peripheral localization of this active Rod subcluster and its pronounced loss following RAO. Overall, this study provides a comprehensive spatial cell atlas of the whole eye and offers novel spatial-resolution insights into the pathological mechanisms of RAO, serving as a valuable resource for deciphering the physiological and pathological landscapes of the eye at single-cell resolution.

Acute retinal artery occlusions present with sudden, painless monocular vision loss and are equivalent to cerebral strokes. The diagnosis is made on ocular fundus examination facilitated by fundus photography and optical coherence tomography. Management of acute retinal artery ischemia requires a collaborative approach among emergency department, ophthalmology, and stroke neurology providers. In the acute setting, patients should undergo a standard stroke evaluation. There are currently no widely accepted therapies for acute retinal artery occlusions. So-called "conservative treatments," such as anterior chamber paracentesis, ocular massage, and hemodilution, have no benefit and should not be pursued. Recent meta-analyses and reviews from experts have suggested a possible treatment effect for intravenous tPA within 4.5hours of vision loss or intra-arterial tPA within 6hours of vision loss for patients with acute central retinal artery occlusion. Ongoing clinical trials evaluating intravenous thrombolysis within 4.5hours of vision loss will hopefully provide definite answers. In the interim, it is essential to educate providers and patients about the importance of calling emergency services when experiencing acute vision loss to ensure immediate transfer to a facility affiliated with a stroke center, where timely diagnosis, evaluation, and treatment of acute retinal ischemia can occur.

Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of medium-sized arteries, and histologic confirmation is often challenging. Temporal artery biopsy (TAB) is established for suspected giant cell arteritis (GCA), but is rarely performed in PAN. We describe a 27-year-old Japanese man who presented with melena and acute visual loss in the right eye. Contrast-enhanced computed tomography revealed multiple visceral aneurysms involving the hepatic, renal, and mesenteric arteries, with active extravasation from a jejunal artery aneurysm. Ophthalmologic evaluation confirmed central retinal artery occlusion. Renal biopsy showed no evidence of vasculitis. During hospitalization, he developed a new medullary infarction, and re-examination revealed induration of the superficial temporal artery. TAB was therefore performed and demonstrated neutrophil-rich necrotizing arteritis with fibrinoid change, supporting the diagnosis of PAN. To contextualize the diagnostic role of TAB in PAN, we reviewed the literature and identified 21 TAB-confirmed cases including this patient. Most reported TAB-confirmed PAN cases underwent biopsy because GCA was initially suspected, and the histopathologic findings were heterogeneous; a neutrophil-predominant necrotizing pattern with fibrinoid change-particularly in the absence of multinucleated giant cells-may prompt reconsideration beyond GCA. The diagnostic yield of TAB in unselected PAN has not been studied, and the available evidence is limited to case reports and TAB-based cohorts. Nevertheless, TAB may be considered a pragmatic option for histologic confirmation when conventional biopsy sites are impractical or high risk, particularly in the presence of cranial ischemic manifestations or temporal-artery abnormalities.

The purpose of this report is to document the occurrence of transient central retinal artery occlusion (CRAO) as a rare and serious ocular complication in a patient with granulomatosis with polyangiitis (GPA), emphasizing the potential vision-threatening nature of this condition. A 49-year-old male with a known diagnosis of GPA presented with transient CRAO. The case was analyzed to understand the ocular manifestations associated with GPA and the challenges in its management. The patient exhibited a transient CRAO, highlighting the potential for severe ocular complications in the context of GPA. Transient CRAO is a rare but serious vision-threatening complication of GPA. This case underscores the importance of early diagnosis and timely management in patients with ocular manifestations of GPA. Financial disclosure: No financial support was received for this case report. None of the authors has any proprietary interests or conflicts of interest related to this submission. It is not simultaneously being considered for publication at any other journal.