Three donor-matched iPSC lines derived from human postmortem dura mater for modeling neurodegenerative diseases.

The skull bone marrow-meninges-brain axis: A new sentinel for neuroinflammation regulation in ischemic stroke.

To examine the impact of angiographic markers on endovascular therapy (EVT) outcomes in patients with lateral sinus dural arteriovenous fistulas (LSDAVFs). We analyzed the data of 81 patients who completed their first EVT session for LSDAVFs between December 2011 and February 2025 at our institute. Angiograms obtained before EVT were evaluated for LSDAVF characteristics. Shunt patterns were categorized as direct sinus fistula type, compartmental sinus channel type, mural channel type, and bridging vein shunt type. Sinovenous outflow patency was evaluated using the combined conduit score (CCS), a 9-point scoring system with scores ranging from 0 (total occlusion) to 8 (full patency). Multivariate logistic regression and Cox regression were used to identify key parameters associated with complete LSDAVF obliteration after EVT. Of the 81 patients, 46 (56.8%) achieved immediate obliteration after EVT. Multivariate logistic regression revealed that a CCS <4, jugular bulb involvement, and ipsilateral meningohypophyseal trunk supply were independent parameters associated with immediate obliteration. After a median imaging follow-up duration of 11.4 months, 36 out of 60 patients (60%) achieved complete obliteration without further treatment. Multivariate Cox regression revealed that a CCS <4 was independently associated with complete obliteration (HR 3.061, P=0.006). LSDAVFs with sinovenous outflow restriction, indicated by a CCS <4, were more likely to be obliterated after EVT compared with those without outflow restriction. In patients with LSDAVFs, the CCS may assist in outcome prediction and therapeutic decision-making.

Endoscopic occipital interhemispheric contralateral approach for middle-third falcine meningiomas: A venous-sparing consecutive case series.

The cerebellar tentorium, composed of 2 laminae of dura mater, is an essential structure that separates the posterior and middle cerebral fossae. As it has a dural sinus within its 2 laminae, it carries significant risk potential. Cranium shape may affect its morphological properties. The cephalic index (CI) can easily describe a ratio of the length and width of the cranium. People may have different CI values individually, or some populations have a typical cranium shape that gives a clue for the CI. The aim of the present study was to investigate the morphometric properties of the cerebellar tentorium related to CI groups. A total of 594 participants’ (304 women and 290 men) computed tomographic angiography image series were included in the presented study, retrospectively. We evaluated cerebellar tentorium’s morphometric properties, its length, and its angle according to the McRae line, and compared these measurements in relation to CI. All morphometric evaluations were completed using free licensed Horos Software v.3.3.6. According to our results, morphometric properties tended to be higher in men than in women. We also found morphometric differences in the cerebellar tentorium among the CI groups. However, our results demonstrated that age was not effective on the cerebellar tentorium’s morphometric organization. Cerebellar tentorium has a potential risk for injuries during posterior cranial fossa approaches. A number of studies aimed to evaluate patients’ position during surgical interventions. However, the morphometric properties of cerebellar tentorium were not considered during the evaluation of patients’ surgical position in previous studies. Though statistically significant, observed differences and correlations in tentorial morphometry were weak and likely of limited clinical utility. Findings contribute to anatomical reference data but may not be useful for inferring surgical guidance.

Repair of large dura mater defects is hindered by excessive inflammation, cerebrospinal fluid leakage, and insufficient regeneration. In this study, a Janus-bilayer artificial dura mater (SCPM) was fabricated via coaxial electrospinning, consisting of a polycaprolactone (PCL) hydrophobic layer, a PCL core, and a poly(p-dioxanone) shell incorporating 4Sr15CeBG. The exudate can undergo spontaneous 'pumping' from the hydrophilic base layer to the hydrophobic top layer, while maintaining excellent drug delivery capability with a well-structured core-shell structure. The resulting core-shell fibrous scaffold exhibited stable mechanical performance with a tensile strength of approximately 5 MPa and controlled degradation behavior. SCPM-3 demonstrated optimal biocompatibility, with L929 and RAW264.7 cell viabilities exceeding 110% at day 3 and hemolysis rates below 5%. The scaffold significantly reduced intracellular reactive oxygen species levels, promoted macrophage polarization toward the M2 phenotype, decreased TNF-α and IL-1β secretion, and increased TGF-β and IL-10 secretion. In a rat dural defect model, SCPM-3 accelerated neodura formation, enhanced angiogenesis, reduced inflammation and adhesion, and produced continuous, well-organized collagen deposition by postoperative day 14. These results demonstrate that encapsulation of SrCeBG combined with a coaxial fibrous architecture enables safe, immunomodulatory, and effective dura mater regeneration.

This case involved the elderly woman with alcoholic cirrhosis and periodontal disease who developed suppurative spondylitis, multiple abscesses, and multi-organ failure. Although she initially improved following intensive care treatment, she developed calcification of both the myocardium and the cranial dura mater on day 70. Post-septic dural calcification has not been previously reported, and this case represents the first such report. As a hypothesis regarding the mechanism of onset, it is presumed that the effects of sepsis extended to the dura mater, and that abnormal calcification of the dura mater progressed due to the effects of various therapeutic interventions. These findings were limited to imaging results and had no clinical implications. This unique case adds a new cause to the list of known etiologies for cranial dural calcification.

ABSTRACTThe dural venous sinuses are the main conduit for cerebral blood flow to drain from the head back to the heart. Pathology of these sinuses has significant impacts on cerebral blood volume and intracranial pressure, indicating that these veins have an important role in cerebral hemodynamics. Active and modifiable mechanisms of sinus diameter control may present an opportunity for physiological or pathological regulation of venous blood flow. Here, we characterized the molecular and anatomical properties of dural vascular smooth muscle cells (SMCs) using RNA-sequencing and immunohistochemistry, demonstrating that artery-like SMCs are exclusive to sinus vessels. An ex vivo pressurized sinus preparation from mice was used to functionally characterize the vasodynamics of the sinus and its corresponding bridging veins. We found that the sinus contains dynamically contractile SMCs and constricts to both pressure and contractile agonists, while the bridging veins do not. We further demonstrated that these sinus SMCs exhibit dynamic calcium signaling that is responsive to contractile stimuli. These results reveal a contractile SMC phenotype localized to dural venous sinuses and demonstrate that sinus vessels possess active, artery-like mechanisms for regulating cerebral venous outflow.

Dissection of the corpus callosum is a well-established treatment option for patients with pharmaco-resistant epilepsy. Both partial and complete callosotomies are performed to reduce seizure burden. In recent years, multiple minimally invasive variations of corpus callosotomy have been suggested. These techniques, however, can be cost and time demanding, which limits their use to specialized centers in high-resource settings. We present our experience with a mini-open microsurgical technique. Our technique employs a parasagittal longitudinal incision followed by a small craniotomy and retractorless interhemispheric dissection. Neuronavigation was used to find an operative corridor between bridging veins to the sagittal sinus. Postoperative computed tomography and magnetic resonance images were analyzed to describe the size of craniotomies and the disconnected area of the corpus callosum. We performed 38 partial callosotomies in 24 patients over a period of 5 years. The median age at the initial surgery was 8.5 years (IQR 5.9-11.9). In 15 patients (62.5%), the first surgery was a posterior callosotomy. The average size of the craniotomy since adoption of this technique was 43.6 mm by 27.8 mm but decreased to an average of 35.8 mm by 24.2 mm in the last 2 years. The mean operating time per procedure was 99.6 minutes (SD ±28.9 minutes). Surgeries were performed by attendings, fellows, and residents in 28, 6, and 4 cases, respectively. We experienced no complications with this approach in the investigated period. Mini-open partial callosotomy is a safe and efficient procedure that minimizes the morbidity associated with a larger approach. It can be performed and taught in conventionally equipped microsurgical neurosurgery units, thus contributing to further emphasize the use of epilepsy surgery also in resource constrained environments.

Moyamoya disease and angiogenesis: a quantitative analysis of key angiogenic markers.

Artificially degradable dura mater substitutes are critical for protecting brain tissue and cerebrospinal fluid (CSF), yet current materials struggle with biomechanical mismatches, uncontrolled degradation, permeability, and limited bioactivity. To address this, we engineered an absorbable bacterial cellulose (BC)-based composite dural substitute via microbial synergism, combining strontium-doped hydroxyapatite (Sr-HAp) biomimetic mineralization with cellulase enzymatic functionalization. A sustainable alternating assembly technique yielded gradient mineralization, constructing a multilayered micro-nano architecture within the BC matrix. With ceramic content tuned from 52.7% to 82.7%, the BC-SrHAp membrane exhibited remarkable mechanical enhancement, 578%-1172% higher compressive strength and 9.4%-58.4% greater tensile strength than pure BC. The rationally designed 3D nano-network architecture reinforces BC fibers while retarding degradation kinetics, enabling controlled release of Sr2 +/Ca2 + ions. The sustained ion elution boosted fibroblast activity (enhanced by 8.0%-10.1%), migration (enhanced by 18.2%-22.7%), and osteoblast proliferation (enhanced by 3.2%-16.8%). Moreover, the dense mineralized mesh reduced CSF leakage by 12.8%, surpassing clinical sealing thresholds. Crucially, cellulase enabled degradation-regeneration coupling, ensuring material resorption aligned with tissue repair kinetics. Comprehensive evaluation confirms the BC-SrHAp6-Cel3 composite membrane's potential as an artificial dural material, effectively balancing structural support, controlled degradation, biological activity, and cerebrospinal fluid shielding properties. Its balanced performance underscores high translational potential for complex dural reconstructions.

Critical-size defects (CSDs) in craniofacial reconstruction refer to osseous gaps that fail to heal spontaneously, increasing the risk of neurological impairment and craniofacial dysmorphology. Despite decades of investigation, controversy still exists surrounding the definition of CSDs, with criteria varying across species, experimental models, and patient populations. This review integrates past and contemporary perspectives, while examining how age, dura mater biology, and stem cell dynamics influence regenerative potential. For instance, pediatric patients demonstrate increased healing capacity due to their metabolically active dura and enriched stem cell niches, while aging patients face diminished osteogenesis due to chronic age-related inflammation (inflammaging) and stem cell senescence. Meanwhile, experimental models highlight that defect size, embryonic bone origin, and proximity to cranial sutures affect healing, thus highlighting the need for standardized, age-specific definitions of CSDs. Advances in biomaterials, like bioceramic composites and dura-integrative hydrogels, show promise in advancing osteogenesis and vascularization across age groups. Additionally, dura-targeted regenerative strategies that leverage dural signaling represent a novel and promising solution to cranial repair. However, the transition from translational to clinical practice remains limited due to the lack of standardization in the literature and scarce long-term clinical data. In this review, CSD re-classification is proposed through an age-stratified framework that integrates biological, structural, and clinical variables. Standardizing models will help isolate determinants of calvarial healing and refine treatment strategies.

Epidural fibrosis (EF) refers to the non-physiological scar formation at the site where a surgical incision is made to access the spinal canal. This condition often results in functional disability and pain following spinal surgery and is a common and difficult-to-treat contributor to Failed Back Surgery Syndrome (FBSS). This study aimed to investigate the effectiveness of platelet-rich fibrin (PRF) clots, vein grafts, or a combination of both in reducing epidural fibrosis after laminectomy in rats. One hundred adult Sprague-Dawley male rats, weighing 300 ± 55g, were equally and randomly assigned into five groups (n = 20): the control, laminectomy, PRF, vein graft, and PRF/vein graft groups. The control group consisted of normal, untouched rats that did not undergo anesthesia, surgical exposure, laminectomy, or sham operation. Lumbar laminectomy was performed at L3-L5 in the laminectomy, PRF, vein graft, and PRF/vein graft groups. On postoperative day 30, outcomes were assessed in two predefined independent subsets within each group. Ten rats per group were used for macroscopic epidural adhesion scoring after surgical-site reopening, whereas the remaining ten rats per group were used for histopathological, morphometric, and qRT-PCR analyses of IL-6 and TGF-β1 expression. Therefore, the effective analytical sample size was n = 10 animals per group for each endpoint category, not n = 20 per group. The primary endpoint was histological epidural fibrosis score at day 30; all other macroscopic, morphometric, inflammatory, and molecular outcomes were secondary endpoints. The EF area was significantly reduced in all treatment groups compared with the laminectomy group. Overall, the vein graft-containing groups showed the strongest reductions in adhesion, scar density, dura mater thickness, and IL-6/TGF-β1 expression. The combined PRF/vein graft treatment was generally more favorable than PRF alone but was often comparable to vein graft alone, indicating that a consistent superiority of the combined approach over vein graft alone was not demonstrated. Vein graft-containing treatments reduced histological and molecular markers of epidural fibrosis in this rat laminectomy model. The combined PRF/vein graft approach showed favorable anti-inflammatory and anti-fibrotic effects, but it was not consistently superior to the vein graft alone across all assessed endpoints. Therefore, the findings should be interpreted as preliminary preclinical evidence supporting further investigation of vein graft-based local barrier strategies rather than direct evidence of a superior combination therapy or a clinically ready approach.

Calcitonin gene-related peptide (CGRP) is a central mediator in migraine and an endogenous vasodilator in the trigeminovascular system. Its role in subarachnoid hemorrhage (SAH), remains uncertain, particularly in patients receiving CGRP-targeted migraine therapy at the time of hemorrhage. This study examined whether CGRP blockade administered shortly before experimental SAH affects outcome and whether early SAH is associated with altered trigeminovascular CGRP signaling. CGRP-mediated vasodilation was first assessed ex vivo in rat and mouse cerebral arteries using wire myography to identify the most suitable species for SAH experiments. Experimental pre-chiasmatic SAH was then induced in rats. At 24h, body weight, rotating pole performance, mechanical sensitivity, and capsaicin evoked CGRP release from dura mater and trigeminal ganglion were evaluated in SAH and sham animals. In a separate intervention arm, rats received vehicle or the anti-CGRP monoclonal antibody fremanezumab, 30mg/kg intravenously, 15min before SAH. Functional outcome, neurological scoring, body weight, and survival were followed for 14 days. Rat basilar arteries showed markedly greater CGRP-induced dilation than mouse basilar arteries, supporting rat as the relevant model. At 24h after SAH, body weight was reduced whereas periorbital and plantar von Frey thresholds were unchanged. Capsaicin-evoked CGRP release from dura mater was significantly reduced after SAH, while trigeminal ganglion release was unaffected, consistent with early peripheral trigeminovascular peptide release. Fremanezumab treated animals showed higher cerebral blood flow 5min after SAH and improved rotating pole performance at 48h compared with vehicle treated animals. No significant differences were observed in composite survival, defined as freedom from spontaneous death or euthanasia at humane endpoint, body weight trajectory, well-being score, or composite neurological score at the 14day follow up. Experimental SAH is associated with early impairment of releasable CGRP in dura mater, supporting acute trigeminovascular involvement after hemorrhage. Pre-existing CGRP blockade did not worsen overall 14-day outcome in this model of SAH, but seemingly improved early functional recovery and the temporal pattern of disease progression. These findings suggest stage-dependent effects of CGRP signaling in SAH and support further study of CGRP-targeted therapies in cerebrovascular disease.

Meningeal lymphatic vessels (MLVs) have emerged as critical regulators of central nervous system (CNS) homeostasis, and MLVs dysfunction has been implicated in various neurological disorders. A comprehensive assessment of MLVs' morphology and function is therefore essential for understanding their role in CNS physiology and disease. This protocol describes an integrated method for evaluating MLVs in mice using four key techniques: Intra-cisterna-magna (i.c.m.) injection of fluorescent tracers, live imaging of cervical lymph nodes (CLNs), meningeal dissection, and whole-mount staining. First, the 30 G needle is connected to the syringe and infusion pump via a polyethylene (PE) tube. After the mouse is anesthetized, the dura mater is exposed by blunt dissection of the neck muscles, and the injection needle is inserted into the cisterna magna (CM) to deliver the tracer into the cerebrospinal fluid (CSF) with precise control. Tracer drainage to the CLNs can be visualized in real time, while subsequent meningeal dissection and whole-mount staining enable detailed morphological analysis of the dorsal MLVs. The entire procedure can be completed within 3 h, encompassing i.c.m. injection, tissue perfusion, skull isolation, and placement in fixative solution. This protocol can also be adapted for intracranial drug delivery or combined with molecular analyses, as the meningeal dissection procedure is compatible with fresh, unfixed tissues suitable for RNA and protein extraction.

The default mode network (DMN) is a central, large-scale brain network implicated in a range of cognitive functions and neuropsychiatric disorders, such as major depressive disorder (MDD). Studying the DMN's complex dynamics in animal models provides invaluable insights into its function in both healthy and pathological states. However, performing stable, long-term, large-scale electrophysiological recordings from the multiple deep and distributed nodes of the DMN in awake, behaving mice remains a significant challenge. Here, a novel two-phase surgical protocol is presented to create a large (4 mm × 7.6 mm), durable, and resealable cranial window in mice. The procedure is designed to preserve the integrity of the dura mater, which is paramount for long-term brain health and recording stability. This window enables simultaneous, repeated, longitudinal recordings from over 1,000 electrodes by combining surface-level micro-electrocorticography (µECoG) with two high-density intracranial electrode probes, providing unprecedented access to the DMN. This technique provides a robust platform for multi-modal, multi-scale interrogation of network-wide electrophysiological dynamics over several weeks, opening new avenues for investigating the neuroplastic changes underlying the pathophysiology of brain disorders and for evaluating the chronic effects of novel therapeutics.

Acute traumatic cervical spinal cord injury frequently leads to severe cord edema, elevated intraspinal pressure, reduced spinal cord perfusion, and progressive neurological deterioration. Conventional bony decompression via laminectomy may provide limited relief, as the non-elastic dura mater can continue to constrain the swollen spinal cord. Expansion duroplasty is designed to address this limitation by enlarging the intradural space using an artificial dural substitute, allowing controlled expansion of the injured spinal cord. This protocol describes patient positioning, selection of laminectomy levels based on preoperative magnetic resonance imaging, dural opening technique, preparation of an artificial dural substitute, suturing sequence, and postoperative strategies to mitigate cerebrospinal fluid leakage. Critical steps are highlighted to ensure a watertight closure, minimize infection risk, and optimize gravity-dependent wound drainage. Representative results include postoperative imaging demonstrating restoration of the cerebrospinal fluid space, reduced dural constriction, and absence of significant pseudomeningocele formation. This method is intended for patients with severe cervical spinal cord swelling within 72 hours of injury and can be implemented in centers with microsurgical spine expertise as an adjunct to standard decompression procedures.

Surgical resection of a single brain metastasis improves survival. However, lesions in the parasagittal perirolandic region pose a therapeutic challenge due to high eloquence and the “gravity–buoyancy conflict.” Under physiological conditions, cerebrospinal fluid buoyancy reduces the brain’s effective weight by approximately 95%. Loss of this support upon opening the dura leads to gravitational sag of the hemisphere. This increased functional weight pulls the bridging veins downward, creating a valve-like effect and a mechanical kink at the rigid dural entry point.A 59-year-old male presented with a 3-cm cystic metastasis in the posterior superior frontal gyrus (SFG). Intraoperatively, gravitational sag of the tumor-expanded gyrus created significant downward traction on the vein of Trolard. This tension induced a potential focal kink at the rigid dural interface, resulting in flow stasis, recognized by distal colorless depletion and dark, pulsatile proximal blood. Consent for the procedure and image publication was obtained, and Queen’s University Ethics Board approved this report.Wide splitting of both the superior frontal and precentral sulci allowed for necessary safe access to the tumor and potential decoupling of the tumor-bearing SFG from the hemisphere. To resolve the dural entry kink, a strategic wide arachnoid release was performed along the vein to provide vascular laxity. After early cyst drainage and unloading the pathological weight, the created laxity allowed the vein to return to its physiological location, resolving the stasis. Untethering the vein from its arachnoid anchors allowed the vein to tolerate necessary traction on the vessel wall during tumor resection (Video 1).

ObjectiveCalcitonin gene related peptide (CGRP) is a central mediator in migraine and can trigger attacks in susceptible individuals. Therapies targeting CGRP or its receptor provide clinical benefit, but treatment responses vary. This suggests that local factors regulating CGRP availability and signalling within migraine relevant tissues may influence its biological effects. The extent and functional relevance of CGRP degradation at the dura mater, including possible effects on biomarker detection, remain insufficiently characterised.MethodsProteomic analyses were used to identify human αCGRP (hαCGRP) degradation fragments generated in rat meningeal preparations. Functional properties of full-length hαCGRP and selected degradation fragments were assessed at the dura mater, in isolated arteries, in mast cell degranulation assays, and at CGRP receptors in vitro. Fragment interactions with a CGRP ELISA were examined to assess potential interference with detection of full-length CGRP. Male Sprague Dawley rats were used for the ex vivo experiments.ResultshαCGRP disappeared rapidly in the meningeal environment and reduced transdural resistance in the dura mater. Seven predominant degradation fragments accounted for ~ 81.5% of the detected fragment pool. None of the fragments showed agonist activity at the CGRP receptor or altered dural resistance or mast cell degranulation. In vascular assays, the fragments were likewise inactive, with the exception of the C-terminal fragment hαCGRP11−37, which displayed weak competitive antagonism at the CGRP receptor. This was confirmed at both the human and rat CGRP receptor in vitro. Although the identified fragments were not directly detected by the CGRP ELISA, selected fragments interfered with intact hαCGRP measurements, indicating that degradation products can influence biomarker readout.ConclusionLocal degradation of hαCGRP at the dura mater primarily generates fragments without measurable vascular, immune, or receptor activating effects. The main consequence of this processing appears to be reduced hαCGRP bioavailability rather than formation of secondary bioactive signalling peptides. At the same time, fragment dependent interference in ELISA based detection indicates that local hαCGRP metabolism may affect interpretation of CGRP biomarker measurements in migraine relevant tissues.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-026-02390-3.

The coexistence of an intracranial aneurysm (IA) and meningioma (MNG) is a rare clinical entity (0.13-1.17%). However, the prevalence of clinically occult MNGs may be underestimated, as routine vascular imaging often misses small lesions. We present two female patients with a history of multiple or recurrent IAs and prior endovascular treatment. During surgical clipping via a pterional approach, suspicious dural lesions-hypervascularization and thickening around the anterior clinoid process-were incidentally identified, despite being invisible on preoperative imaging. Intraoperative biopsies confirmed these lesions as MNGs. While the exact pathogenesis or underlying association remains speculative, these cases highlight the critical importance of unexpected intraoperative findings. Neurosurgeons must maintain high vigilance and strongly consider active biopsy of abnormal dura mater encountered during IA clipping, particularly in patients with multiple IAs or previous endovascular treatments.