The basic helix–loop–helix factors play a central role in neuronal differentiation and nervous system development, which involve the Notch and signal transducer and activator of transcription (STAT)/small mother against decapentaplegic signaling pathways. Neural stem cells differentiate into three nervous system lineages, and the suppressor of cytokine signaling (SOCS) and von Hippel-Lindau (VHL) proteins are involved in this neuronal differentiation. The SOCS and VHL proteins both contain homologous structures comprising the BC-box motif. SOCSs recruit Elongin C, Elongin B, Cullin5(Cul5), and Rbx2, whereas VHL recruits Elongin C, Elongin B, Cul2, and Rbx1. SOCSs form SBC-Cul5/E3 complexes, and VHL forms a VBC-Cul2/E3 complex. These complexes degrade the target protein and suppress its downstream transduction pathway by acting as E3 ligases via the ubiquitin–proteasome system. The Janus kinase (JAK) is the main target protein of the E3 ligase SBC-Cul5, whereas hypoxia-inducible factor is the primary target protein of the E3 ligase VBC-Cul2; nonetheless, VBC-Cul2 also targets the JAK. SOCSs not only act on the ubiquitin–proteasome system but also act directly on JAKs to suppress the Janus kinase–signal transduction and activator of transcription (JAK-STAT) pathway. Both SOCS and VHL are expressed in the nervous system, predominantly in brain neurons in the embryonic stage. Both SOCS and VHL induce neuronal differentiation. SOCS is involved in differentiation into neurons, whereas VHL is involved in differentiation into neurons and oligodendrocytes; both proteins promote neurite outgrowth. It has also been suggested that the inactivation of these proteins may lead to the development of nervous system malignancies and that these proteins may function as tumor suppressors. The mechanism of action of SOCS and VHL involved in neuronal differentiation and nervous system development is thought to be mediated through the inhibition of downstream signaling pathways, JAK-STAT, and hypoxia-inducible factor–vascular endothelial growth factor pathways. In addition, because SOCS and VHL promote nerve regeneration, they are expected to be applied in neuronal regenerative medicine for traumatic brain injury and stroke.

Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide. Here, we report that ADMSCs differentiate to the cholinergic phenotype of neurons by the SOCS7-derived BC-box motif peptide. At operations for patients with neurological disorders, a small amount of subcutaneous fat was obtained. Two weeks later, adipose-derived mesenchymal stem cells (ADMSCs) were isolated and cultured for a further 1 to 2 weeks. Flow cytometry analysis for characterization of ADMSCs was performed with CD73, CD90, and CD105 as positive markers, and CD14, CD31, and CD56 as negative markers. The results showed that cultured cells were compatible with ADMSCs. Immunocytochemical studies showed naïve ADMSCs immunopositive for p75NTR, RET, nestin, keratin, neurofilament-M, and smooth muscle actin. ADMSCs were suggested to be pluripotent stem cells. A peptide corresponding to the amino-acid sequence of BC-box motif derived from SOCS7 protein was added to the medium at a concentration of 2 μM. Three days later, immunocytochemistry analysis, Western blot analysis, ubiquitination assay, and electrophysiological analysis with patch cramp were performed. Immunostaining revealed the expression of neurofilament H (NFH), choline acetyltransferase (ChAT), and tyrosine hydroxylase (TH). In addition, Western blot analysis showed an increase in the expression of NFH, ChAT, and TH, and the expression of ChAT was more distinct than TH. Immunoprecipitation with JAK2 showed an increase in the expression of ubiquitin. Electrophysiological analysis showed a large holding potential at the recorded cells through path electrodes. The BC-box motif peptide derived from SOCS7 promoted the cholinergic differentiation of ADMSCs. This novel method will contribute to research as well as regenerative medicine for cholinergic neuron diseases.

Background: Atypical facial pain (AFP) differs from typical trigeminal neuralgia (TTN) in clinical features and pathophysiology. Internal neurolysis (IN) has been proposed as a treatment for refractory AFP; however, objective intraoperative assessment methods remain limited. Methods: We retrospectively analyzed 20 consecutive patients with AFP who underwent IN. Intraoperative findings revealed superior cerebellar artery (SCA) compression in five cases, venous compression in four, and no vascular compression in 11. When vascular compression was identified, the vessel was dissected and mobilized before performing IN. For comparison, we reviewed a cohort of patients with TTN and SCA compression who underwent microvascular decompression with arterial transposition. Intraoperative sclerosis was graded (0–6 points) according to appearance, stiffness, and adhesion. Pain severity was evaluated using the Barrow Neurological Institute (BNI) pain score. Results: A total of 20 patients underwent IN for AFP, including 12 females and eight males, with a mean age of 62.5 years (range, 32–82 years). Postoperatively, 15 patients (75%) achieved BNI I–II, indicating significant pain relief, while 5 patients (25%) achieved BNI III, reflecting moderate residual pain. Median follow-up was 18 months (range, 6–24 months). No major surgical complications were observed. Higher sclerosis scores and moderate-to-severe adhesions were significantly associated with favorable BNI outcomes ( P = 0.03). Conclusion: IN is an effective and safe treatment for refractory AFP, particularly in patients with trigeminal sclerosis. Comparison with patients with TTN highlights distinct pathophysiology and treatment strategies, while SCA transposition is curative in TTN, AFP requires dissection and IN.

Background: Trigeminal neuralgia (TN) is most commonly caused by neurovascular compression; however, a subset of patients present without identifiable vascular contact, for whom the optimal surgical strategy remains controversial. Methods: Between February 2022 and August 2025, 157 patients underwent microsurgical treatment for TN at our institution. This study represents a retrospective analysis of a prospectively maintained surgical database. Thirty patients without radiological or intraoperative evidence of neurovascular compression were treated with superficial epineurial incision. Pain outcomes were evaluated using the Barrow Neurological Institute (BNI) pain intensity scale, and postoperative complications were assessed. Results: Immediate postoperative pain relief (BNI I–II) was achieved in all patients. At 12 months, 27 (90%) patients maintained favorable outcomes. Recurrence was defined as deterioration to BNI grade III or higher requiring additional medication or reintervention; 3 (10%) patients met this definition. Transient facial numbness occurred in 3 (10%) patients and resolved within 3 months. No permanent dysesthesia, anesthesia dolorosa, or corneal complications were observed. Conclusion: In this exploratory retrospective case series, superficial epineurial incision was feasible and associated with favorable short-term pain control with limited sensory morbidity in carefully selected patients with classical TN without neurovascular compression. Interpretation of these findings should be made in the context of the baseline, and further studies with larger cohorts and longer follow-up are required.

Background: Microvascular decompression (MVD) is the standard surgical treatment for classical trigeminal neuralgia (TN) with evident neurovascular compression. Internal neurolysis (IN) offers an alternative microsurgical technique. However, the physiological basis of symptom relief remains unclear. This study analyzed surgical outcomes and intraoperative conduction changes in patients without apparent vascular compression. Methods: Among 158 patients who underwent MVD for TN between February 2022 and March 2025, 14 had no definite vascular compression on preoperative 3D Magnetic resonance cisternography/angiogram-fusion imaging or intraoperative inspection and underwent IN. Conduction changes were classified into four patterns: (1) shortened latency with increased amplitude, (2) unchanged latency with increased amplitude, (3) unchanged latency and amplitude, and (4) recovery from unmeasurable to measurable conduction. Results: The mean age was 64.9 years with an equal sex distribution. The right and left trigeminal nerves were affected in 10 and 4 patients, respectively. Nine patients had typical TN, and five had atypical features. Five patients had recurrent pain after previous MVD. Excellent outcomes (Barrow Neurological Institute [BNI] I–II) were achieved in 11 of 14 patients (78.6%), while 3 patients (21.4%) had partial pain relief (BNI III). Typical TN patients more frequently demonstrated conduction patterns 1 or 4, whereas atypical TN patients more often exhibited patterns 2 or 3. Conclusion: IN was associated with favorable clinical outcomes and intraoperative electrophysiological improvement in patients with TN without apparent vascular compression. These findings provide physiological observations accompanying clinical improvement following IN.

Background: Lumboperitoneal (LP) shunt surgery is an established treatment for idiopathic normal pressure hydrocephalus (iNPH). In Japan, patients undergoing LP shunt surgery are often hospitalized for several days to more than one week after surgery, even in uncomplicated cases, reflecting concerns regarding early complications, cerebrospinal fluid overdrainage, and discharge readiness in older adults. This study evaluated the feasibility and short-term safety of a perioperative optimization pathway for planned short-stay hospitalization after LP shunt surgery. Methods: This single-center retrospective before-and-after cohort study included 15 consecutive patients who underwent elective LP shunt surgery. Six patients were managed using a conventional hospitalization pathway, whereas nine patients were treated under a short-stay pathway targeting discharge after one postoperative night. Key perioperative modifications included a uniform higher initial programmable valve pressure (level 7), structured discharge education, scheduled postoperative analgesia, waterproof wound sealing permitting early showering, and early outpatient follow-up with head computed tomography for staged valve pressure adjustment. The primary outcome was 30-day safety, defined as readmission, reoperation, or major postoperative complications. Results: Baseline characteristics were generally comparable between groups, although the short-stay group was slightly older and had more frequent antithrombotic therapy. Mean hospital length of stay was shorter in the short-stay group than in the conventional group (3.7 ± 2.0 vs. 9.7 ± 0.8 days; median, 3 vs. 9.5 days). Orthostatic headache requiring valve adjustment occurred in three conventional cases but in none of the short-stay patients. No patients in the short-stay group required readmission or reoperation within 30 days. Conclusions: In this pilot before-and-after study, a short-stay LP shunt pathway incorporating perioperative optimization and individualized discharge decision-making was feasible and was not associated with an apparent increase in early adverse events. These findings should be interpreted as exploratory and may support further evaluation of short-stay management strategies for selected patients undergoing LP shunt surgery in Japan.