Mitochondrial Calcium Uniporter (MCU) is Involved in an Ischemic Postconditioning Effect Against Ischemic Reperfusion Brain Injury in Mice.

The phenomenon of ischemic postconditioning (PostC) is known to be neuroprotective against ischemic reperfusion (I/R) injury. One of the key processes in PostC is the opening of the mitochondrial ATP-dependent potassium (mito-KATP) channel and depolarization of the mitochondrial membrane, triggering the release of calcium ions from mitochondria through low-conductance opening of the mitochondrial permeability transition pore. Mitochondrial calcium uniporter (MCU) is known as a highly sensitive transporter for the uptake of Ca2+ present on the inner mitochondrial membrane. The MCU has attracted attention as a new target for treatment in diseases, such as neurodegenerative diseases, cancer, and ischemic stroke. We considered that the MCU may be involved in PostC and trigger its mechanisms. This research used the whole-cell patch-clamp technique on hippocampal CA1 pyramidal cells from C57BL mice and measured changes in spontaneous excitatory post-synaptic currents (sEPSCs), intracellular Ca2+ concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents under inhibition of MCU by ruthenium red 265 (Ru265) in PostC. Inhibition of MCU increased the occurrence of sEPSCs (p = 0.014), NMDAR currents (p < 0.001), intracellular Ca2+ concentration (p < 0.001), and dead cells (p < 0.001) significantly after reperfusion, reflecting removal of the neuroprotective effects in PostC. Moreover, mitochondrial depolarization in PostC with Ru265 was weakened, compared to PostC (p = 0.004). These results suggest that MCU affects mitochondrial depolarization in PostC to suppress NMDAR over-activation and prevent elevation of intracellular Ca2+ concentrations against I/R injury.

Pre-treatment systemic inflammation response index and systemic immune inflammation in patients with primary central nerve system lymphoma as a useful prognostic indicator.

PURPOSE: The systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII) are based on neutrophil, monocyte, platelet, and lymphocyte counts. The SIRI and SII are used to predict the survival of patients with malignant tumors. It is well known that the inflammatory immune response is closely related to cancer occurrence and progression. In the present study, we evaluated the potential prognostic significance of SIRI and SII in patients with primary central nervous system lymphoma (PCNSL). METHODS: Fifty-eight consecutive patients were enrolled in this study between November 2006 and May 2022. Among the 58 patients, 47 patients with sufficient blood test data and follow-up were analyzed. The patients with steroid intake at the time point of the blood test and higher C-reactive protein were excluded. RESULTS: The median follow-up and survival times were 31 and 36 months, respectively. The optimal cutoff SIRI value was based on the receiver operating characteristic curve (ROC) for overall survival (OS) and stratified patients into low (< 1.43 × 109/L, n = 22) and high (≥ 1.43 × 109/L, n = 25) SIRI groups. The optimal cutoff SII value based on the ROC for OS stratified patients into low (< 694.9, n = 28) and high (≥ 694.9, n = 19) SII groups. A low SIRI value was associated with longer OS (p = 0.006). Furthermore, a low SII value was associated with longer OS (p = 0.044). The prognostic factors associated with prolonged survival in univariate analysis using the Cox proportional hazard model were age < 65 years, low SIRI, and low SII. The multivariate analysis demonstrated that age < 65 years and low SIRI independently predicted longer OS. CONCLUSION: Simple, less expensive, and routinely ordered preoperative blood count assessments such as SIRI and SII predict the OS of patients with PCNSL. This study demonstrated that PCNSL is associated with pre-treatment systemic immune-inflammation states.

Medulla and cervical cord contrast-induced encephalopathy detected by neuromonitoring during coil embolization of posterior circulation aneurysms.

Understanding the risks of contrast-induced encephalopathy (CIE), a serious complication of contrast agents, is crucial in endovascular treatment. We present the case of a 73-year-old woman who developed CIE in the medulla and cervical cord during coil embolization for unruptured left basilar-superior cerebellar artery and basilar artery tip aneurysms. The CIE was identified via neuromonitoring. In this case, spinal cord ischemia might have occurred due to reduced perfusion pressure after inserting the distal access catheter (DAC) in the vertebral artery. Multiple injections of contrast medium via the DAC during coil embolization likely contributed to an unusual form of CIE. Extreme caution is warranted during endovascular treatments involving the posterior circulation, due to the relatively high incidence of contrast-mediated encephalopathy, which can lead to severe consequences such as perforator infarction. Neuromonitoring is very useful for the early detection of neurological changes, particularly because intraoperative angiography may not reveal all irregularities.

Long-term outcomes and potential predictive recurrence factors after endonasal endoscopic surgical treatment of symptomatic Rathke's cleft cysts.

Although patients with symptomatic Rathke's cleft cysts (RCCs) receive surgical treatment, recurrence sometimes occurs after surgery. However, the mechanism underlying recurrence remains unclear. We evaluated the outcomes of RCC decompression over a long-term follow-up period. We retrospectively reviewed the medical records of 35 patients with symptomatic RCC who underwent endonasal endoscopic surgery (EES) at our institution between 2008 and 2023. Patients' characteristics, intraoperative findings, and postoperative follow-up outcomes were evaluated. A univariate regression model was used to identify the predictors of recurrence. The median patient age was 48.0 years, and 74.2% of the patients were female. The mean follow-up duration was 94.7 ± 47.6 months. Cyst content recurrence was observed in 15 patients (42.8%). Five patients (14.2%) with symptomatic recurrence underwent reoperation. Postoperative vision improved in all 23 patients (100%); headaches improved in 20 patients (90.9%). A new hormonal deficit occurred in two patients (5.7%). Complications included intraoperative cerebrospinal fluid (CSF) leak in 10 patients (28.5%), postoperative CSF leak in two patients (5.7%), permanent diabetes insipidus in two patients (5.7%), and postoperative infection in three patients (8.5%). Univariate analyses revealed that the position of the anterior pituitary lobe (p = 0.019) and preoperative visual disturbances (p = 0.008) significantly affected recurrence after surgery. Although EES was efficient, the recurrence rate was relatively high over a long-term period. The anterior pituitary lobe position and preoperative visual disturbances were significantly associated with recurrence. The anterior-inferior position can predict a high risk of recurrence before surgery.

Intraoperative monitoring of trigeminal neuralgia: a technical note.

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.

Ischemic Postconditioning Reduces NMDA Receptor Currents Through the Opening of the Mitochondrial Permeability Transition Pore and KATP Channel in Mouse Neurons.

Ischemic postconditioning (PostC) is known to reduce cerebral ischemia/reperfusion (I/R) injury; however, whether the opening of mitochondrial ATP-dependent potassium (mito-KATP) channels and mitochondrial permeability transition pore (mPTP) cause the depolarization of the mitochondrial membrane that remains unknown. We examined the involvement of the mito-KATP channel and the mPTP in the PostC mechanism. Ischemic PostC consisted of three cycles of 15 s reperfusion and 15 s re-ischemia, and was started 30 s after the 7.5 min ischemic load. We recorded N-methyl-D-aspartate receptors (NMDAR)-mediated currents and measured cytosolic Ca2+ concentrations, and mitochondrial membrane potentials in mouse hippocampal pyramidal neurons. Both ischemic PostC and the application of a mito-KATP channel opener, diazoxide, reduced NMDAR-mediated currents, and suppressed cytosolic Ca2+ elevations during the early reperfusion period. An mPTP blocker, cyclosporine A, abolished the reducing effect of PostC on NMDAR currents. Furthermore, both ischemic PostC and the application of diazoxide potentiated the depolarization of the mitochondrial membrane potential. These results indicate that ischemic PostC suppresses Ca2+ influx into the cytoplasm by reducing NMDAR-mediated currents through mPTP opening. The present study suggests that depolarization of the mitochondrial membrane potential by opening of the mito-KATP channel is essential to the mechanism of PostC in neuroprotection against anoxic injury.

Melatonin-Induced Postconditioning Suppresses NMDA Receptor through Opening of the Mitochondrial Permeability Transition Pore via Melatonin Receptor in Mouse Neurons.

Mitochondrial membrane potential regulation through the mitochondrial permeability transition pore (mPTP) is reportedly involved in the ischemic postconditioning (PostC) phenomenon. Melatonin is an endogenous hormone that regulates circadian rhythms. Its neuroprotective effects via mitochondrial melatonin receptors (MTs) have recently attracted attention. However, details of the neuroprotective mechanisms associated with PostC have not been clarified. Using hippocampal CA1 pyramidal cells from C57BL mice, we studied the involvement of MTs and the mPTP in melatonin-induced PostC mechanisms similar to those of ischemic PostC. We measured changes in spontaneous excitatory postsynaptic currents (sEPSCs), intracellular calcium concentration, mitochondrial membrane potential, and N-methyl-D-aspartate receptor (NMDAR) currents after ischemic challenge, using the whole-cell patch-clamp technique. Melatonin significantly suppressed increases in sEPSCs and intracellular calcium concentrations. The NMDAR currents were significantly suppressed by melatonin and the MT agonist, ramelteon. However, this suppressive effect was abolished by the mPTP inhibitor, cyclosporine A, and the MT antagonist, luzindole. Furthermore, both melatonin and ramelteon potentiated depolarization of mitochondrial membrane potentials, and luzindole suppressed depolarization of mitochondrial membrane potentials. This study suggests that melatonin-induced PostC via MTs suppressed the NMDAR that was induced by partial depolarization of mitochondrial membrane potential by opening the mPTP, reducing excessive release of glutamate and inducing neuroprotection against ischemia-reperfusion injury.

Post-surgical Hearing Improvement in a Case of Jugular Foramen Schwannoma Despite the Lack of Response in a Preoperative Auditory Brainstem Response Test.

We report a rare case involving improved hearing after surgery for a jugular foramen schwannoma despite the lack of response during the preoperative auditory brainstem response (ABR) test. A left jugular foramen tumor was diagnosed in a 79-year-old man with hearing loss. No response was observed during the preoperative ABR test. However, his hearing improved after surgery using the lateral suboccipital approach. Following Gamma Knife radiation to the residual tumor post-surgery, the ABR test detected V waves. The hearing of patients with cerebellopontine angle tumors can improve even when there is no response during the preoperative ABR test.

Awake Craniotomy for Astrocytoma in the Left Frontal Lobe Using Augmented Reality Superimposing Tumor and White Matter Tracts: 2-Dimensional Operative Video.

Augmented reality (AR) is expected to serve as an assistive intraoperative technology in neurosurgery.1 Awake craniotomy (AC) for gliomas benefits the extent of resection, survival, and postoperative neurofunctional outcomes.2 In AC, it is critical to understand the cortical and subcortical anatomy.3 We describe the use of AR superimposing tumor and deep white matter tracts in AC. A 29-year-old right-handed woman presented to a local hospital after an episode of generalized convulsions. MRI of the head revealed a widely spreading tumor in the left middle frontal gyrus. After a left frontal craniotomy while the patient was asleep, AR was used to indicate the tumor boundary with subcortical fibers including the corticospinal tract, inferior fronto-occipital fasciculus, and cingulate fasciculus. We performed AR-assisted removal of the tumor on the surface of the middle frontal gyrus. On subcortical stimulation (SCS) of the frontal aslant tract and inferior fronto-occipital fasciculus, the patient stopped naming objects in the picture-naming test, while SCS of the left cingulate gyrus caused the patient to mistake colors in the Stroop test. The subcortical fibers identified by AR coincided with the sites of symptom elicitation by SCS. We eventually removed a large part of the tumor. Postoperative MRI confirmed 96.2% resection. The patient was discharged without any new neurological deficits. AC with AR is useful for resection of gliomas in the dominant hemisphere. The patient consented to the procedure and to the publication of her image. The ethics committee of our hospital does not require approval for case reports.

Giant skull base periosteal chondroma treated with endonasal endoscopic surgery: illustrative case.

BACKGROUND: Intracranial chondroma is an extremely rare type of tumor composed of mature hyaline cartilaginous tissues. No previous cases of skull base periosteal chondroma have been presented. OBSERVATIONS: A 31-year-old male had progressive memory loss and diminished motivation for the previous 1.5 years. Magnetic resonance imaging revealed a giant tumor with partial calcification arising from the upper clivus and extending to the prepontine cistern. Compression of the brainstem and hypothalamus was significant. Surgery was performed and intentionally limited to an intracapsular resection with endoscopic endonasal surgery (EES), and the brainstem and hypothalamus were successfully decompressed. Pathological examination findings showed a composition of hyaline cartilage with chondrocyte clusters. Genetic testing with next-generation sequencing indicated alternations in IDH1 R132C, KDR Q472H, IDH2 I142L, and TP53 P72R. On the basis of these findings, a diagnosis of periosteal chondroma was made. Postoperatively, complete relief from all symptoms was noted, and MRI one year later showed no evidence of tumor regrowth. LESSONS: This is the first known report of skull base periosteal chondroma. Genetic testing was useful for confirming the diagnosis, and EES was effective for treatment. Should such a tumor show adhesion to an important structure, an intracapsular excision can be beneficial for avoiding complications.

Preoperative Blood Counts Predict Overall Survival in Patients Undergoing Surgical Removal of Brain Metastasis.

OBJECTIVE: The prognosis for patients with cancer with brain metastasis (BM) requiring surgical removal is quite limited. Preoperative prognostic factors can provide meaningful information to surgeons, oncologists, and patients. This study evaluated the preoperative blood counts in patients with BM who were treated with surgical removal. METHODS: Between January 2011 and November 2021, 221 consecutive surgeries were conducted on 198 patients with BM. Among the 198 patients, 188 patients with sufficient blood test data and follow-up were analyzed in this study. The tumors originated from the lungs (n = 102, 54.3%), colon (n = 26, 13.3%), breast (n = 13, 6.9%), kidney (n = 8, 4.3%), stomach (n = 6, 3.2%), and others (n = 33, 17.6%). The blood test data included neutrophils, lymphocytes, monocytes, eosinophils, basophils, red blood cell count, hemoglobin, and albumin. RESULTS: The median follow-up and median survival times were both 11 months (range: 0-139 months). Higher neutrophil-lymphocyte ratio ≥ 3.17, platelet-lymphocyte ratio ≥112.7, systemic immune-inflammation index ≥594.4, systemic inflammation response index ≥1.25 were unfavorable predictors of prognosis for the patients treated with surgical removal for BM (P < 0.001). Furthermore, lower lymphocyte-monocyte ratio < 2.33 and prognostic nutritional index < 48.5 were unfavorable predictors. CONCLUSIONS: Simple, less expensive, routinely ordered preoperative blood count assessments, such as the neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index, and prognostic nutritional index, can predict the overall survival of patients treated with surgical removal for BM.

Passive Approximator Vascular Closure Device Use in Patients with Shallow Femoral Artery Depth Increases Puncture-site Complications in Neuroendovascular Treatment.

OBJECTIVE: Puncture-site complications in interventional radiology sometimes cause severe conditions. Vascular closure devices play an important role in preventing puncture-site complications. Vascular closure devices are divided into 2 types, the directly suturing or clipping type (active approximators) and adherent sealant types (passive approximators). However, which types of vascular closure device are the safest and most effective for achieving hemostasis remains unclear. We analyzed the efficacy of each type of vascular closure device and risk factors for puncture-site complications. METHODS: This study investigated 327 consecutive cases of neuroendovascular surgery using a transfemoral procedure during a 2-year study period. Passive approximators (Angioseal [St Jude Medical, Saint Paul, MN] and Exoseal [Cordis Corporation, Miami, FL]) were mainly used in the first half and active approximators (Perclose [Abbot Vascular, Santa Clara, CA]) in the second. We compared groups and estimated risk factors for puncture-site complications. RESULTS: All procedures were successful. Comparing groups with and without puncture-site complications, use of passive approximators and ≥3 antithrombotic medications tended to be more frequent and distance from skin to femoral artery and body mass index tended to be lower in the group with complications without significance. The cutoff for femoral artery depth calculated from a receiver operating characteristic curve was 16.43 mm. Multivariate analysis revealed ≥3 antithrombotic medications (P = 0.002, OR 15.29, 95% CI 2.76-85.76) and passive approximator use in patients with femoral artery depth <16.43 mm (P < 0.001, OR 17.08, 95% CI 2.95-57.80) were significantly higher in the group with puncture-site complications. CONCLUSIONS: Passive approximator use in patients with shallow femoral artery depth increases puncture-site complications in neuroendovascular treatment.

Delayed Intracranial Parenchymal Changes After Aneurysmal Coil Embolization Procedures for Unruptured Intracranial Aneurysms.

BACKGROUND: With the recent advances in endovascular treatment devices, it has become standard in wide-neck or large intracranial aneurysms to perform coil embolization with adjunctive techniques. However, device-related perioperative complications have been reported because of the use of more complex systems. OBJECTIVE: To investigate patients who developed multiple parenchymal lesions after undergoing coil embolization for treating an unruptured intracranial aneurysm. METHODS: This study investigated 305 consecutive patients who underwent coil embolization of unruptured intracranial aneurysms between 2015 and 2017. Delayed inflammatory changes referred to the delayed observation of multiple cerebral white matter lesions on follow-up magnetic resonance imaging at an area corresponding to the perfused area of the treatment target vessel. The timing and pattern of onset, device used, the combined use of adjunctive techniques, and the clinical course after steroid treatment were retrospectively investigated. RESULTS: The 7 patients (2.3%) who showed delayed inflammatory changes were all women with a mean age of 59 yr. A mean duration from treatment to onset was 28 d. Symptoms were convulsions in 3 patients, hemiplegia in 2 patients, and homonymous hemianopia in 1 patient. All 7 patients were treated with adjunctive technique including stents, double catheter method, and balloon assist. Response to steroid treatment was satisfactory both clinically and on imaging in all 7 patients. Skin patch test was positive for nickel allergy in 2 patients. CONCLUSION: Clinicians must be fully aware of symptomatic delayed inflammatory changes may occur after endovascular aneurysmal treatment with the use of various devices.

Endovascular treatment of idiopathic intracranial hypertension caused by multiple venous sinus stenoses.

BACKGROUND: Idiopathic intracranial hypertension (IIH) shows symptoms by elevating intracranial pressure. Although sinus stenosis has been detected in many patients with IIH, the role of sinus stenosis in IIH remains obscure. Endovascular treatment for IIH due to transverse sinus stenosis has been frequently documented; however, IIH due to multiple sinus stenoses including the superior sagittal sinus (SSS) is rare. Here, we report a case of IIH due to multiple sinus stenoses treated by sinus stenting. CASE PRESENTATION: A 47-year-old woman suffered from intractable headache with IIH presented with stenosis of the right transverse and SSS. Stent placement was carried out since intracranial hypertension and trans-stenotic cerebral venous pressure gradient (CVPG) were presented, and her intractable headache disappeared. CONCLUSION: IIH can be caused by venous sinus stenoses and stent placement could be an appropriate treatment in patients who demonstrated a CVPG.

Ischemic postconditioning prevents surge of presynaptic glutamate release by activating mitochondrial ATP-dependent potassium channels in the mouse hippocampus.

A mild ischemic load applied after a lethal ischemic insult reduces the subsequent ischemia-reperfusion injury, and is called ischemic postconditioning (PostC). We studied the effect of ischemic PostC on synaptic glutamate release using a whole-cell patch-clamp technique. We recorded spontaneous excitatory post-synaptic currents (sEPSCs) from CA1 pyramidal cells in mouse hippocampal slices. The ischemic load was perfusion of artificial cerebrospinal fluid (ACSF) equilibrated with mixed gas (95% N2 and 5% CO2). The ischemic load was applied for 7.5 min, followed by ischemic PostC 30 s later, consisting of three cycles of 15 s of reperfusion and 15 s of re-ischemia. We found that a surging increase in sEPSCs frequency occurred during the immediate-early reperfusion period after the ischemic insult. We found a significant positive correlation between cumulative sEPSCs and the number of dead CA1 neurons (r = 0.70; p = 0.02). Ischemic PostC significantly suppressed this surge of sEPSCs. The mitochondrial KATP (mito-KATP) channel opener, diazoxide, also suppressed the surge of sEPSCs when applied for 15 min immediately after the ischemic load. The mito-KATP channel blocker, 5-hydroxydecanoate (5-HD), significantly attenuated the suppressive effect of both ischemic PostC and diazoxide application on the surge of sEPSCs. These results suggest that the opening of mito-KATP channels is involved in the suppressive effect of ischemic PostC on synaptic glutamate release and protection against neuronal death. We hypothesize that activation of mito-KATP channels prevents mitochondrial malfunction and breaks mutual facilitatory coupling between glutamate release and Ca2+ entry at presynaptic sites.

Endovascular Therapy for the Steal Phenomenon due to the Innominate Artery Severe Stenosis and Bilateral Internal Carotid Artery Severe Stenosis.

BACKGROUND: Symptomatic innominate artery stenosis presenting as hemodynamic bilateral cerebral ischemia is uncommon. We present a rare case of the severe stenosis of the origin of an innominate artery and severe stenosis of bilateral internal carotid artery that induced hemodynamic cerebral ischemia after ipsilateral axillary artery-bilateral femoral artery bypass and was treated with stent replacement of the innominate artery and right internal carotid artery. CASE REPORT: A 64-year-old woman who previously had undergone right axillary artery-bilateral femoral artery anastomosis for abdominal aorta high obstruction had been suffering from chronic dizziness and so visited our department. Findings of the examination included the severe stenosis of the origin of an innominate artery and severe stenosis of bilateral internal carotid artery, causing hemodynamic cerebral ischemia. She underwent stent replacement of the innominate artery and right carotid artery stenting via a right transbrachial approach. Her symptoms were relieved postoperatively. DISCUSSION: For the sake of improving the hemodynamic cerebral ischemia, we performed stent replacement for innominate artery stenosis and right carotid artery stenting. Endovascular treatment of subclavian and innominate artery disease is a safe procedure. In addition, for the protection of thromboembolic migration, we performed balloon protection of the external carotid artery and filter protection of the internal carotid artery. CONCLUSIONS: Stent replacement for these lesions can be performed safely with the right approach and protection methods, even when the only accessible route is the right brachial artery.