The cerebral ischemia-reperfusion injury (CIRI) induced by endovascular treatment represents a research challenge. Microglial pyroptosis plays a critical role in the neuroinflammatory damage associated with CIRI. Gasdermin D (GSDMD) is a key executor of pyroptosis, mediating plasma membrane rupture. Interestingly, research on pyroptosis has long focused on cell membrane rupture. We further hypothesize that cytoskeletal collapse during pyroptosis may facilitate cell rupture. This new perspective will contribute to a comprehensive understanding of the mechanisms of morphological changes during pyroptosis. Recent research has proposed disulfidptosis, an emerging form of cell death characterized by cytoskeletal collapse. Therefore, we speculated that disulfidptosis might occur concurrently with pyroptosis-associated cell rupture, and investigated whether disulfiram (DSL) could inhibit microglial pyroptosis and the associated disulfidptosis-related changes in a CIRI model. Middle cerebral artery occlusion (MCAO) was established on rats, and the optimal dosage of DSL was determined. Neurological function, infarct volume, vascular diameter, cellular morphology, and key molecular mediators of microglial pyroptosis and disulfidptosis were tested. Furthermore, microglial mitochondrial fragmentation was investigated at the subcellular structural level. High-dose DSL (500 mg·Kg-1d-1) significantly improved neurological function in rats. Moreover, high-dose DSL reduced infarct size and attenuated cellular shrinkage in the ischemic penumbra. GSDMD and SLC7A11 were co-localized in microglia. DSL suppressed the expression of pyroptosis-related proteins, including GSDMD-N-terminal, caspase-1 p10, and cleaved caspase-11. In addition, DSL mitigated SLC7A11 loss and inhibited the expression of NOX4 and ARP2. At the mitochondrial level, DSL alleviated microglial mitochondrial fragmentation and downregulated the expression of DRP1 and VDAC1. Following CIRI, disulfiram suppressed pyroptosis by inhibiting the caspase-1/11-GSDMD pathway and attenuated disulfidptosis-like changes via modulation of the SLC7A11-NOX4-ARP2 axis, suggesting its potential neuroprotective effect.

Curcumin augments mitophagy via Nrf2-PINK1-mediated, Parkin-dependent ubiquitination to suppress ferroptosis in post-cardiac arrest brain injury.

The integrity of the vascular endothelium is fundamental to regulating cardio-metabolic and neurological functions. Endothelial dysfunction (ED) is a key driver of atherosclerosis and is strongly linked to the pathogenesis of heart disease, peripheral arterial disease, and stroke. This review describes the relationship between dietary patterns and endothelial health, focusing on observational and experimental studies that investigate the protective effects of healthy dietary patterns in the maintenance of endothelial integrity and prevention of ED. Plant-based diets, including Mediterranean and Dietary Approaches to Stop Hypertension (DASH) dietary patterns, have been linked to improvement of endothelial function through multiple mechanisms such as increased nitric oxide bioavailability, reduced oxidative stress and inflammation, and fostering a healthy gut microbiome. Traditional Japanese, Nordic, and Palaeolithic dietary patterns also show potential cardiovascular benefits through improved vascular biomarkers and significant anti-inflammatory effects, though evidence on effects on endothelial function remains less established. The consequences of poor endothelial health extend to all systems, and the brain is one of the organs crucially affected by ED. ED has been increasingly recognised as a critical contributor to cognitive decline, dementia, and stroke, largely accounted and explained by mechanisms impairing cerebral blood flow, neuronal metabolism, neuro-vascular coupling and compromised integrity of the blood-brain barrier. This review highlights the importance of maintaining endothelial health as a protective strategy for cognitive function and reduction of dementia risk. Adherence to dietary patterns with protective effects on endothelial integrity may represent an effective strategy to promote lifelong health for both the heart and brain.

Integrated miRNA-proteomic profiling identifies chronic vesicle-trafficking and proteostasis disruptions after mild traumatic brain injury.

Long-term neurological and neurocognitive deficits in adults prenatally exposed to methylmercury: Minamata disease.

Neuroprotective potential of orphenadrine in focal cerebral ischemia: A neurobehavioral and mechanistic study.

Liposomal composition tuning improves intranasal brain drug delivery: Role of cholesterol and formulation rheology.

From multi-omics discovery to experimental validation: GPC4 mediates the anti-neuroinflammatory effects of Buyang Huanwu decoction via TLR4/NF-κB signaling in ischemic stroke with Qi deficiency and blood stasis syndrome.

Circulating Ly6Chigh monocyte-derived S100A4+ macrophages exacerbate neuroinflammation and impede recovery of traumatic brain injury.

FGF20 alleviates neuroinflammation in ischemic stroke by modulating microglial polarization via TREM2-TLR4/NF-κB pathway.

NADPH exerts neuroprotection in ischemic stroke by reinforcing blood-brain barrier integrity and stimulating angiogenesis.

β-1, 3-galactosyltransferase 2 promotes cerebral angiogenesis and neurological recovery during the ischemic repair phase through glycosylation modification of TGF-βR(II)/ALK1.

USP8 attenuates ischemic stroke by inhibiting the microglial NF-κB/NLRP3 inflammatory axis via TRAF6 deubiquitination.

Imaging of Epilepsy Surgery, Minimally Invasive Techniques, and Neuromodulation.

The crosstalk between chaperone-mediated autophagy and apoptosis via ATM/p53-mitochondria-dependent signaling contributed to ischemia-induced cerebral injuries.

Brain-heart interactions have garnered considerable interest in the landscape of traumatic brain injury (TBI). This scoping review focused on bradycardia caused by high intracranial pressure (ICP), brainstem injury, autonomic imbalance, hypothalamic-pituitary-adrenal axis disruption, or massive bleeding. The latter condition is attributed to a physiological phenomenon called relative bradycardia (RB). True bradycardia results from underlying physiological or pathological cardiac disorders, whereas RB has different definitions and implications in medical and surgical settings. The former reflects pulse-temperature dissociation, while the latter reflects pulse-pressure dissociation. However, it can reflect an abnormal neurological response called the Cushing reflex. Therefore, bradycardia may indicate imminent shock after TBI associated with torso injuries or high ICP following severe isolated TBI. RB is underrecognized and underappreciated in emergency settings. This review investigated whether RB affects patient survival and neurological function. Physicians should approach patients presentingwith RB with a high index of suspicion and timely management.

Symptomatic basilar invagination (BI) is a complex craniovertebral junction malformation often accompanied by atlantoaxial dislocation (AAD). While posterior reduction and fixation is widely used, anterior odontoidectomy remains essential for decompression. However, conventional odontoidectomy carries a high risk of cerebrospinal fluid (CSF) leakage. We present a novel technique-Transoral Odontoid Process Release, Partial Resection, and Antedisplacement (TOPRA)-designed to achieve effective decompression while reducing CSF leakage risk. Between April 2020 and September 2024, 31 consecutive patients (22 females, 9 males; mean age 40.0 ± 12.92 years) with symptomatic BI underwent the TOPRA procedure. Neurological function was assessed using the Japanese Orthopedic Association (JOA) score. The vertical distance from the odontoid tip to the Chamberlain line (CL) measured on 3D-CT and the cervico-medullary angle (CMA) measured on MRI, were used to assess the degree of compression at the medulla oblongata and upper cervical cord. All patients successfully underwent TOPRA without intraoperative or postoperative CSF leakage. 29 patients with AAD underwent additional posterior reduction and fixation during the same surgical stage. The mean vertical distance from the odontoid tip to the CL decreased significantly from 14.8 ± 3.07mm preoperatively to 9.8 ± 2.14mm postoperatively (p < 0.01). The mean JOA score improved from 11.6 ± 3.49 to 13.6 ± 3.32 at final follow-up (p < 0.01). Follow-up MRI indicated that the CMA increased significantly from 123.0° ± 8.09° preoperatively to 152.8° ± 6.70° (p < 0.01). This study demonstrates that the TOPRA technique can serve as a viable surgical treatment option for symptomatic BI. By preserving the odontoid tip with its ligamentous attachments and displacing the tip anterior-inferiorly, it achieves significant neural decompression while substantially reducing the risk of CSF leakage.

Ischemic stroke (IS) is an acute cerebrovascular disease in which blood circulation to brain tissue and neurological function are impaired due to obstruction of cerebral blood vessels, and it is one of the most common causes of death worldwide. Therapies such as intravenous thrombolysis and endovascular thrombectomy can open occluded cerebral vessels and restore blood flow through reperfusion, but ischemia/reperfusion (I/R) may trigger pathological processes such as oxidative stress, electrolyte disorders, and inflammatory responses, leading to secondary tissue damage such as cerebral edema and intracranial hemorrhage. Therefore, it is crucial to mitigate cerebral ischemia-reperfusion injury (CIRI). Mitochondria, as organelles, usually exist inside cells. However, under the stimulation of CIRI, mitochondria and their components can affect brain tissue cells by transcellular transfer through tunneling nanotubes (TNTs), gap junctions (GJs), and releasing and capturing of extracellular vesicles (EVs), etc. The mitochondrial transcellular transfer therapy for CIRI can reduce oxidative stress damage, improve neuronal energy metabolism, regulate neuroinflammation, and promote neural repair and regeneration. Mitochondrial transcellular transfer is regarded as a promising therapeutic approach for the treatment of CIRI, and in-depth investigation of the mechanism of mitochondrial transcellular transfer is expected to open up a new clinical pathway for the treatment of CIRI. This paper explores the molecular mechanism of mitochondrial transcellular transfer and its effects in the treatment of CIRI, which is expected to broaden clinical therapeutic approaches and provide a new direction for the treatment of CIRI.

To observe the dynamic compensatory characteristics of the leptomeningeal collateral (LMC) circulation in the affected hemisphere of rats with right middle cerebral artery occlusion (MCAO), and to investigate the effects of acupuncture on LMC compensatory efficiency and neuronal function in the cortical M5 region. Additionally, to elucidate the neuroprotective mechanism of acupuncture by exploring the temporal pattern of LMC compensation. This study was divided into 2 parts. Part 1:4 male SD rats were randomly selected for monitoring blood perfusion in the affected LMC and cortical M5 region before ischemia, immediately after ischemia, 3 h and 12 h post-ischemia using laser speckle contrast imaging. Part 2:90 male SD rats were randomly divided into sham operation, model, sham acupuncture, acupuncture, and butylphthalide groups, with 18 rats in each group. Three hours after modeling, acupuncture was applied to bilateral "Neiguan" (PC6) and "Shuigou" (GV26) or non-acupoints (3 mm below the starting point of bilateral axillary midline and 3 mm beside the apex of coccyx) for 30 min. In the butylphthalide group, butylphthalide injection (2.25 mg/kg) was injected into the tail vein once 3 h after successful modeling. Laser speckle blood flow imaging was used to monitor the changes of blood flow perfusion and LMC vascular diameter in LMC and cortical M5 region at different time points before ischemia, immediately after ischemia and 12 h after ischemia. The percentage of cerebral infarction volume was detected by TTC staining. Modified neuropathy symptom score (mNSS) was used to evaluate neurological function. The grip strength of the contralateral upper limb of the rat was detected by the rat grip tester. The ultrastructure of neurons and mitochondria in the M5 region of the affected cortex was observed by transmission electron microscopy. The positive expression of neuronal nuclear protein (NeuN) in the M5 region of the affected cortex was detected by immunofluorescence staining. The content of adenosine triphosphate (ATP) in the cortex of the affected side was detected by colorimetry. Compared with the pre-ischemia state, the blood perfusion in the affected LMC and cortical M5 region were decreased immediately after ischemia (P<0.01). Compared with the immediate ischemia state, the blood perfusion was increased at 3 h post-ischemia (P<0.01, P<0.05). Immediately after ischemia, compared with the sham operation group, the ratio of blood perfusion compared to the baseline level of LMC and cortical M5 in all groups was decreased (P<0.01). At 12 h post-ischemia, the ratio of blood perfusion compared to the baseline level in the LMC and M5 region, and the grip strength of the contralateral upper limb were decreased (P<0.01) in the model group, while the mNSS score and the percentage of cerebral infarction volume were increased (P<0.01). The ultrastructure of neurons and mitochondria in the M5 region of the affected cortex was seriously damaged, and the positive expression of NeuN and the content of ATP in the M5 region were decreased (P<0.01). At 12 h post-ischemia and compared with the model group, the LMC and M5 perfusion ratio, grip strength and the NeuN positive expression and ATP content in the M5 region were significantly increased (P<0.01) in the acupuncture and butylphthalide groups, rather than in the sham acupuncture group, whereas the mNSS score and the percentage of cerebral infarction volume were decreased (P<0.01, P<0.05) in the acupuncture and butylphthalide groups, rather than in the sham acupuncture group. Meanwhile, the ultrastructural damage of neurons and mitochondria was milder in both acupuncture and butylphthalide groups. The compensatory efficacy of the affected LMC in MCAO rats increases through blood flow redistribution at 3 h after ischemia, but declines at 12 h. Acupuncture can enhance the LMC compensatory efficiency, improve cortical M5 blood perfusion, and optimize mitochondrial structure and functional homeostasis, thereby exerting neuroprotective effects.

Intramedullary spinal cord tumors (IMSCTs) are typically treated with maximal safe resection, during which neurosurgeons often monitor for neurological injury using muscle motor evoked potential (mMEP) and direct wave (D-wave) neuromonitoring. The predictive value of changes in D-waves for identifying motor outcomes is underexplored. This study evaluated the utility of D-waves for predicting postoperative motor deficits. Patients who underwent resection of a primary IMSCT with mMEP neuromonitoring from 2003 to 2023 at a tertiary care hospital were identified. Patients who underwent D-wave monitoring in addition to mMEP monitoring were compared to those who underwent mMEP monitoring alone using the Mann-Whitney U-test, chi-square test, and Fisher's exact test. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of D-wave and mMEP monitoring for identifying new neurological deficits immediately postoperatively and at 1 month, 6 months, and last follow-up were calculated. After matching, 125 patients were included (median age 42.0 years; 57.6% male; median follow-up 34.0 months), of whom 88 had both mMEP and D-wave data. The most common pathologies were ependymoma (64.0%) and astrocytoma (17.6%). Patients who did and did not undergo D-wave neuromonitoring had similar preoperative neurological function, primary pathology, tumor grade, and tumor location. D-wave use was associated with increased gross-total resection (88.6% vs 64.9%, p = 0.002) and reduced mortality (5.7% vs 24.3%, p = 0.007), length of stay (5.0 vs 6.0 days, p = 0.033), and 30-day readmission (2.3% vs 13.5%, p = 0.013) and reoperation (1.1% vs 10.8%, p = 0.012). At the 6-month follow-up, D-wave monitoring alone was superior to mMEP and combination monitoring for detecting new motor deficits. D-wave monitoring had peak sensitivity (77.8%) and NPV (96.5%) at 6 months and peak specificity (95.8%) and PPV (76.9%) in the immediate postoperative period. D-wave monitoring was associated with reduced mortality and was more accurate than mMEP monitoring alone or combination monitoring for detecting new postoperative neurological deficits. Further prospective studies are needed to validate these results.