Fully endoscopic microvascular decompression for hemifacial spasm: a clinical study and analysis.

Fully endoscopic microvascular decompression (MVD) of the facial nerve is the main surgical treatment for hemifacial spasm. However, the technique presents distinct surgical challenges. We retrospectively analyzed prior cases to consolidate surgical insights and assess clinical outcomes. Clinical data from 16 patients with facial nerve spasms treated at the Department of Neurosurgery in the First Affiliated Hospital of Bengbu Medical College, between August 2020 and July 2023, were retrospectively examined. Preoperatively, all patients underwent magnetic resonance angiography to detect any offending blood vessels; ascertain the relationship between offending vessels, facial nerves, and the brainstem; and detect any cerebellopontine angle lesions. Surgery involved endoscopic MVD of the facial nerve using a mini Sigmoid sinus posterior approach. Various operative nuances were summarized and analyzed, and clinical efficacy, including postoperative complications and the extent of relief from facial paralysis, was evaluated. Fully endoscopic MVD was completed in all patients, with the offending vessels identified and adequately padded during surgery. The offending vessels were anterior inferior cerebellar artery in 12 cases (75%), vertebral artery in 3 cases (18.75%), and posterior inferior cerebellar artery in 1 case (6.25%). Intraoperative electrophysiological monitoring revealed that the lateral spread response of the facial nerve vanished in 15 cases and remained unchanged in 1 case. Postoperative facial spasms were promptly alleviated in 15 cases (93.75%) and delayed in 1 case (6.25%). Two cases of postoperative complications were recorded-one intracranial infection and one case of tinnitus-both were resolved or mitigated with treatment. All patients were subject to follow-up, with no instances of recurrence or mortality. Fully endoscopic MVD of the facial nerve is safe and effective. Proficiency in endoscopy and surgical skills are vital for performing this procedure.

Keyhole supraorbital eyebrow approach for fully endoscopic resection of tuberculum sellae meningioma.

Background: The fully endoscopic supraorbital trans-eyebrow keyhole approach is a technique utilized for the transcranial resection of tuberculum sellae meningioma (TSM). Surgery is the first choice for TSM treatment. This study aimed to summarize and analyze the safety, feasibility, limitations, and technical requirements of the fully endoscopic supraorbital trans-eyebrow keyhole approach for TSM resection. Methods: Data of 19 TSM fully endoscopic supraorbital trans-eyebrow keyhole approach resections cases (six and 13 on the left and right eyebrows, respectively) were retrospectively analyzed at the Neurosurgery Department of the First Affiliated Hospital of Bengbu Medical College (Bengbu, China) from August 2015 to March 2022. Results: All 19 patients were diagnosed with meningioma (World Health Organization grade I), and according to the scope of tumor resection (EOR), 18 patients (94.7%) had gross total resection (GTR), and one patient (5.3%) had near-total resection (NTR). Preoperative chief complaints were symptomatic visual dysfunction (n = 12), headache and dizziness (n = 6), and accidental discovery (n = 1). Postoperative visual function improved in 83.3% of cases (10/12), and headache and dizziness were relieved in 83.3% of cases (5/6 patients). Postoperative intracranial infection occurred in one case and was cured by external drainage of the lumbar cistern and anti-infective treatment. Two cases of frontal lobe injury were discharged after conservative treatment. There was no postoperative olfactory dysfunction, eyelid ptosis, cerebrospinal fluid leakage, or death. There were no reports of disease recurrence or death during the 3-month follow-up at an outpatient clinic or by telephone. Conclusion: Fully endoscopic TSM resection through the keyhole approach is safe and feasible. It can be used to explore angles that cannot be seen under a microscope and show the true value of endoscopy technology. The endoscopic equipment and technical skills of the surgeon and surgical team are important in this technique.

Toxic effects of endoplasmic reticulum stress transducer BBF2H7-derived small peptide fragments on neuronal cells.

Aggregation, fibril formation, and deposition of amyloid ß (Aß) protein are believed to be the central pathogeneses of Alzheimer's disease (AD). Numerous studies have shown that fibril formation is promoted by preformed seeds at the beginning of the aggregation process. Therefore, aggregated molecules that promote fibrillization of Aß protein as seeds could affect the pathology. We recently found that approximately 40 amino acid hydrophobic peptides, BBF2H7-derived small peptide (BSP) fragments, are generated via intramembranous cleavage under endoplasmic reticulum (ER) stress conditions. Interestingly, similar to Aß protein, the fragments exhibit a high aggregation propensity and form fibril structures. It has been noted that ER stress is involved in the pathogenesis of AD. In this study, we examined the effect of BSP fragments on aggregation and cytotoxicity of Aß1-40 protein, which is generated as a major species of Aß protein, but has a lower aggregative property than Aß1-42 protein. We demonstrated that BSP fragments promote aggregation of Aß1-40 protein. Aggregates of Aß1-40 protein mediated by BSP fragments also exhibited potent neurotoxicity. Our findings suggest the possibility that BSP fragments affect accumulation of Aß proteins and are involved in the pathogenesis of AD.

Production of BBF2H7-derived small peptide fragments via endoplasmic reticulum stress-dependent regulated intramembrane proteolysis.

Intramembrane cleavage of transmembrane proteins is a fundamental cellular process to produce important signals that elicit biological responses. These proteolytic events are known as regulated intramembrane proteolysis (RIP). ATF6 and BBF2H7 are transmembrane basic leucine zipper transcription factors and are subjected to RIP by site-1 protease (S1P) and site-2 protease (S2P) sequentially in response to endoplasmic reticulum (ER) stress. However, the detailed mechanisms responsible for RIP of the transcription factors, including the precise cutting sites, are still unknown. In this study, we demonstrated that S1P cleaves BBF2H7 just before the RXXL S1P recognition motif. Conversely, S2P cut at least three different sites in the membrane (next to Leu380, Met381, and Leu385), indicating that S2P cleaves the substrates at variable sites or via a multistep process. Interestingly, we found BBF2H7-derived small peptide (BSP) fragments located between the S1P and S2P cleavage sites in cells exposed to ER stress. Major type of BSP fragments was composed of 45 amino acid including partial transmembrane and luminal regions and easily aggregates like amyloid ß (Aß) protein. These results advance the understanding of poorly characterized ER stress-dependent RIP. Furthermore, the aggregable peptides produced by ER stress could link to the pathophysiology of neurodegenerative disorders.

Neuronal activity-dependent local activation of dendritic unfolded protein response promotes expression of brain-derived neurotrophic factor in cell soma.

Unfolded protein response (UPR) has roles not only in resolving the accumulation of unfolded proteins owing to endoplasmic reticulum (ER) stress, but also in regulation of cellular physiological functions. ER stress transducers providing the branches of UPR signaling are known to localize in distal dendritic ER of neurons. These reports suggest that local activation of UPR branches may produce integrated outputs for distant communication, and allow regulation of local events in highly polarized neurons. Here, we demonstrated that synaptic activity- and brain-derived neurotrophic factor (BDNF)-dependent local activation of UPR signaling could be associated with dendritic functions through retrograde signal propagation by using murine neuroblastoma cell line, Neuro-2A and primary cultured hippocampal neurons derived from postnatal day 0 litter C57BL/6 mice. ER stress transducer, inositol-requiring kinase 1 (IRE1), was activated at postsynapses in response to excitatory synaptic activation. Activated dendritic IRE1 accelerated accumulation of the downstream transcription factor, x-box-binding protein 1 (XBP1), in the nucleus. Interestingly, excitatory synaptic activation-dependent up-regulation of XBP1 directly facilitated transcriptional activation of BDNF. BDNF in turn drove its own expression via IRE1-XBP1 pathway in a protein kinase A-dependent manner. Exogenous treatment with BDNF promoted extension and branching of dendrites through the protein kinase A-IRE1-XBP1 cascade. Taken together, our findings indicate novel mechanisms for communication between soma and distal sites of polarized neurons that are coordinated by local activation of IRE1-XBP1 signaling. Synaptic activity- and BDNF-dependent distinct activation of dendritic IRE1-XBP1 cascade drives BDNF expression in cell soma and may be involved in dendritic extension. Cover Image for this issue: doi. 10.1111/jnc.14159.