Current Neuropharmacology - Online First

Amyloid-beta-targeting monoclonal antibodies (mAbs) for Alzheimer's disease frequently induce amyloid-related imaging abnormalities with hemorrhage (ARIA-H), yet systematic comparisons of ARIA-H incidence across therapeutic agents remain limited. Post-approval research prioritizes dosing over mechanism, leaving unresolved whether ARIA-H variations originate from intrinsic mAb properties. We address two gaps: comparative ARIA-H risk stratification among clinically available/investigational mAbs, and elucidation of structural/functional features influencing ARIA-H susceptibility.

A systematic comparison of seven mAbs (donanemab, aducanumab, bapineuzumab, lecanemab, gantenerumab, crenezumab, solanezumab) was conducted, analyzing clinical trial data and molecular characteristics.

ARIA-H incidence ranked as follows (highest to lowest): donanemab > aducanumab > bapineuzumab > lecanemab > gantenerumab > crenezumab > solanezumab. Five mAb-specific determinants emerged: (1) Types of Aβ Binding: Enhanced clearance of mature amyloid plaques correlated with elevated ARIA-H risk. (2) Polymer binding Affinity: Reduced small oligomer-binding capacity predicted higher ARIA-H incidence. (3) Epitope location: N-terminal-targeting mAbs showed greater ARIA-H incidence vs. mid/C-terminal binders. (4) Fc region structure: IgG4-based constructs showed higher ARIA-H incidence than IgG1 analogs. (5) Clearance kinetics: Rapid attainment of amyloid reduction thresholds amplified ARIA-H incidence.

We identify a risk hierarchy for ARIA-H among anti-Aβ mAbs and link specific mAb biophysical properties—Aβ binding type, affinity for soluble oligomers, epitope specificity, Fc structure, and plaque clearance dynamics—directly to ARIA-H pathogenesis.

These findings establish a mechanistic framework for ARIA-H risk and provide concrete molecular predictors to guide antibody engineering strategies. Prioritizing mAbs with controlled amyloid clearance, C-terminal binding domains, and IgG1 frameworks may enhance therapeutic safety, advancing precision immunotherapy for Alzheimer's disease.

Facial nerve injury induces autophagy and apoptosis in facial nerve nucleus motoneurons of the CNS, impairing nerve regeneration and functional recovery. The function of P2Y2R after facial nerve injury remains to be determined. This study hypothesizes that inhibiting P2Y2R may play a protective role in facial nerve injury by modulating the autophagy signaling pathway.

An in vivo mouse model of facial nerve crush injury was utilized in this study. Mice received either a P2Y2R agonist or antagonist through intrathecal injections of 10 μL/daily for 4 weeks. This study measured facial nerve function, examined fibrogenesis, and analyzed expression of autophagy regulatory proteins. In an in vitro experiment, NSC34 cells were treated with a P2Y2R agonist or an antagonist, and changes in the levels of phosphorylated PI3K, Akt, and mTOR, as well as autophagy regulatory proteins determined.

Inhibition of P2Y2R significantly increased autophagy levels and enhanced facial nerve function. These protective outcomes were linked to the suppression of phosphorylated PI3K, Akt, and mTOR signaling pathways.

The study suggests that P2Y2R inhibition may improve facial nerve function by improving autophagy, making it a promising therapeutic approach for treating facial nerve injury.

Numerous studies have demonstrated that efgartigimod is effective in treating myasthenia gravis (MG) across various patient populations. However, there is limited evidence regarding its use in patients with new-onset acetylcholine receptor antibody-positive generalized MG (AChR-gMG). Therefore, this study aimed to investigate the real-world safety and effectiveness of efgartigimod in Chinese patients with new-onset anti-cholinergic receptor (AChR)- gMG.

This prospective study was conducted in 29 patients with new-onset AChR-gMG, with a three-month follow-up. The Myasthenia Gravis Activities of Daily Living (MG-ADL) score, Quantitative Myasthenia Gravis score, prednisone dose, laboratory data, and adverse events were assessed at every follow-up visit.

At 4, 8, and 12 weeks, the mean change in MG-ADL scores was 8.13  ±  3.66, 7.41  ±  4.22, and 6.37  ±  4.67, respectively. Compared with the baseline, 96% (28/29) of patients achieved an MG-ADL response (defined as a decrease of ≥2 points), with a mean response time of 0.81 ± 0.53 weeks (5.67 ± 3.71 days). After one cycle, 52% (15/29) of patients achieved minimal symptom expression (MSE), while 41% maintained MSE at 12 weeks. Moreover, 89% and 72% of MG-ADL responders sustained for 8 and 12 consecutive weeks, respectively. Additionally, patients with thymomatous MG exhibited a poorer response to efgartigimod and required two infusion cycles. All patients were able to reduce their daily steroid dose, and the mean daily prednisone dose decreased by 10.73 mg per day. The treatment was well tolerated, and a few mild adverse events were reported.

These results demonstrate the clinical significance of efgartigimod in patients with new-onset AChR-gMG, achieving rapid symptom relief and steroid reduction. Additionally, the potential of efgartigimod to serve as a bridge treatment, facilitating a steady transition to long-term conventional immunosuppressive therapy, was demonstrated. Due to limitations in this study, such as a small sample size, larger randomized controlled trials are needed to validate.

Our study showed that efgartigimod is clinically beneficial and offers rapid symptom control in patients with new-onset AChR-gMG. A more aggressive application of efgartigimod in combination with corticosteroids may lead to a smoother therapeutic transition, which will further maintain favorable conditions.

Dysfunction of the pathway between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) may be responsible for the weaker or lack of efficacy of antidepressant drugs in patients suffering from treatment-resistant depression. This study aims to evaluate the behavioural effects of vHPC lesion with ibotenic acid (IBO) in animals subjected to the chronic mild stress (CMS) procedure and treated with either chronic venlafaxine or acute deep brain stimulation (DBS) in the mPFC. In addition, electrophysiological studies are expected to reveal neuromodulatory effects on the function and plasticity of mPFC neurons in response to stress, lesion, and deep brain stimulation (DBS).

Wistar Han rats were exposed to the chronic mild stress model of depression and IBO lesion in vHPC. The effects of both procedures were evaluated in a series of behavioural tests (sucrose test, elevated plus maze, novel object recognition, and social interaction) and in electrophysiological recordings (field potential recording and LTP induction).

The CMS procedure caused a decrease in sucrose consumption, deficits in cognitive function and social interaction, and increased anxiety. The lesion in vHPC with IBO resulted in similar behavioral changes. Repeated (5 weeks) administration of venlafaxine (10 mg/kg, IP) reversed these deficits in stressed animals but was only partially effective in reversing the effects of IBO lesion in HPC. In contrast, the neuromodulation strategy with DBS of the mPFC produced a robust reversal of all behavioural changes observed in both stressed and lesioned rats. The CMS did not affect the amplitude of field potentials in mPFC slices, but the induction of Long-Term Potentiation was impaired in these animals. The IBO lesion significantly reduced the amplitude of Field potentials as compared to unstressed rats. Both repeated venlafaxine and acute DBS normalized these effects of the IBO lesion.

Observed effects were fully normalized by DBS in mPFC but not by venlafaxine, which only partially reversed the IBO lesion-induced effects. The weaker sensitivity of vHPC-lesioned animals to the therapeutic action of venlafaxine provides further evidence that insufficient transmission from the vHPC to the mPFC could be responsible for antidepressant non-response.

These data support the hypothesis that resistance to antidepressant treatment may result from the inability of antidepressants to fully activate the impaired vHPC-PFC pathway, which could be overcome by the neuromodulatory properties of deep brain stimulation.

The COVID-19 pandemic triggered unprecedented changes in the scholarly publishing landscape, particularly in biomedical fields such as Neurosciences and Neuropharmacology. Several journals experienced steep, short-term increases in citation metrics during 2020-2022. However, it remains uncertain whether these surges reflected a sustainable impact or temporary inflation. This study aimed to analyze post-pandemic bibliometric behavior by evaluating the Rate of Change (RoC) in key journal-level indicators from 2013 to 2023.

A retrospective longitudinal study was conducted on 233 neuroscience journals indexed in the Journal Citation Reports. Six indicators were analyzed: Journal Impact Factor (JIF), Eigenfactor Score, Immediacy Index, Article Influence Score, Cited Half-Life, and Total Citations. RoC was calculated for each metric on an annual basis. Mixed-effects models with random intercepts and slopes were constructed to evaluate longitudinal trajectories and identify changes associated with three defined periods: pre-pandemic (2013-2019), pandemic (2020-2022), and post-pandemic (2023). Subgroup analyses assessed journal quartiles and categories to explore variations in impact resilience.

The pandemic period (2020-2022) showed significant increases in RoC for JIF (mean β = +4.85, p = 0.004), Immediacy Index (β = +6.22, p = 0.002), and Total Citations (β = +5.88, p < 0.001). These changes were more prominent in top-quartile journals and those classified under Neuropharmacology. In contrast, alternative metrics such as the Eigenfactor Score and Article Influence Score remained relatively stable across the same period. In 2023, most indicators exhibited a normalization trend, with JIF and Immediacy Index showing marked deceleration in RoC, suggesting a post-pandemic recalibration. Journals with sustained positive trajectories were primarily concentrated in high-impact clusters, with Current Neuropharmacology ranking among the top performers by RoC slope.

The findings demonstrate that the surge in citations during the pandemic was primarily transitory and varied across bibliometric indicators. Traditional metrics like JIF and Immediacy Index were more sensitive to systemic shocks, while influence-based indicators (Eigenfactor and Article Influence Score) showed higher temporal resilience. The application of RoC allowed for a nuanced interpretation of metric trajectories and minimized misinterpretation of short-term spikes. Limitations include reliance on publicly available data and potential lag effects in citation behavior not fully captured within the 10-year window.

This study reveals that pandemic-era citation inflation in Neuroscience journals was largely temporary and metric-dependent. RoC-based modeling offers a reproducible and adaptable approach for assessing the sustainability of bibliometric trends. These insights can help editors, funders, and academic institutions better understand journal performance, make informed decisions about research dissemination, and refine metrics-based evaluation frameworks in the post-pandemic publishing environment.

Cerebral ischemia (CI) is a severe neurological disorder characterized by high incidence and disability rates. Its pathogenesis is complex, involving multiple interrelated biological processes. Among these, intercellular communication has emerged as a key mechanism regulating the damage and recovery phases of CI. It controls information exchange between cells, thereby playing a crucial role in cellular responses to ischemic injury. Understanding how intercellular communication promotes the pathophysiology of CI may provide valuable insights into new therapeutic targets.

To elucidate the role of intercellular communication in CI, recent literature was analyzed, with a focus on how intercellular communication influences cellular behaviors and metabolism. This review integrates data from molecular biology, cellular signaling studies, and cerebral ischemia models.

Studies indicate that intercellular communication significantly influences the progression and outcomes of CI. Intercellular communication not only participates in regulating the inflammatory response following injury but also plays a dual role in neuroprotection and regeneration.

The dual role of intercellular communication—exacerbating damage through inflammatory cascades and promoting recovery through neuroprotective mechanisms—highlights its complex contribution to the pathology of CI. Cellular crosstalk between neurons, glial cells, endothelial cells, and immune cells coordinates the dynamic response to ischemic injury. Understanding these dynamics offers promising opportunities for targeted interventions.

Intercellular communication plays a central role in the mechanisms of injury and repair in cerebral ischemia. By influencing inflammation, neuroprotection, and regeneration, it serves as both a mediator of injury and a potential therapeutic target. Further research is needed to fully elucidate these mechanisms and translate them into effective clinical strategies for treating CI.