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Rapamycin as a preventive intervention for Alzheimer's disease in APOE4 carriers: Targeting brain metabolic and vascular restoration. 雷帕霉素作为APOE4携带者阿尔茨海默病的预防性干预:靶向脑代谢和血管恢复
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-01-29 DOI: 10.4103/NRR.NRR-D-24-01006
Ai-Ling Lin, Chetan Aware
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引用次数: 0
Polysialic acid-Siglec immune checkpoints of microglia and macrophages: Perspectives for therapeutic intervention. 小胶质细胞和巨噬细胞的多唾液酸- siglec免疫检查点:治疗干预的观点。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2024-12-16 DOI: 10.4103/NRR.NRR-D-24-01195
Hauke Thiesler, Herbert Hildebrandt
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引用次数: 0
Neuromodulation technologies improve functional recovery after brain injury: From bench to bedside. 神经调节技术改善脑损伤后的功能恢复:从工作台到床边。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2024-12-07 DOI: 10.4103/NRR.NRR-D-24-00652
Mei Liu, Yijing Meng, Siguang Ouyang, Meng'ai Zhai, Likun Yang, Yang Yang, Yuhai Wang

Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited. This limited plasticity serves as a primary barrier to functional recovery after brain injury. Neuromodulation technologies represent one of the fastest-growing fields in medicine. These techniques utilize electricity, magnetism, sound, and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury. Therefore, this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury. Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury. However, studies report negative findings, potentially due to variations in stimulation protocols, differences in observation periods, and the severity of functional impairments among participants across different clinical trials. Additionally, we observed that different neuromodulation techniques share remarkably similar mechanisms, including promoting neuroplasticity, enhancing neurotrophic factor release, improving cerebral blood flow, suppressing neuroinflammation, and providing neuroprotection. Finally, considering the advantages and disadvantages of various neuromodulation techniques, we propose that future development should focus on closed-loop neural circuit stimulation, personalized treatment, interdisciplinary collaboration, and precision stimulation.

由于受伤的成年哺乳动物中枢神经系统的可塑性有限,自发恢复经常被证明是不适应或不充分的。这种有限的可塑性是脑损伤后功能恢复的主要障碍。神经调节技术是医学中发展最快的领域之一。这些技术利用电、磁、声和光,通过促进重组或长期变化来恢复或优化脑功能,从而支持脑损伤患者的功能恢复。因此,本文旨在全面概述神经调节技术在脑损伤后运动功能恢复中的作用及其潜在机制。许多这些技术被广泛应用于临床实践,并在各种类型的脑损伤中显示出显著的运动功能改善。然而,研究报告了消极的结果,可能是由于刺激方案的不同,观察期的差异,以及不同临床试验参与者的功能损伤的严重程度。此外,我们观察到不同的神经调节技术具有非常相似的机制,包括促进神经可塑性,增强神经营养因子释放,改善脑血流量,抑制神经炎症和提供神经保护。最后,考虑到各种神经调节技术的优缺点,我们建议未来的发展应侧重于闭环神经回路刺激、个性化治疗、跨学科合作和精确刺激。
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引用次数: 0
p21 as an essential regulator of neurogenic homeostasis in neuropathological conditions. P21是神经病理条件下神经源性稳态的重要调节因子。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-01-13 DOI: 10.4103/NRR.NRR-D-24-01255
Valentina Mastrorilli, Stefano Farioli-Vecchioli
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引用次数: 0
Exosomes in neurodegenerative diseases: Therapeutic potential and modification methods. 神经退行性疾病中的外泌体:治疗潜力和修饰方法。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2024-10-22 DOI: 10.4103/NRR.NRR-D-24-00720
Hongli Chen, Na Li, Yuanhao Cai, Chunyan Ma, Yutong Ye, Xinyu Shi, Jun Guo, Zhibo Han, Yi Liu, Xunbin Wei

In recent years, exosomes have garnered extensive attention as therapeutic agents and early diagnostic markers in neurodegenerative disease research. Exosomes are small and can effectively cross the blood-brain barrier, allowing them to target deep brain lesions. Recent studies have demonstrated that exosomes derived from different cell types may exert therapeutic effects by regulating the expression of various inflammatory cytokines, mRNAs, and disease-related proteins, thereby halting the progression of neurodegenerative diseases and exhibiting beneficial effects. However, exosomes are composed of lipid bilayer membranes and lack the ability to recognize specific target cells. This limitation can lead to side effects and toxicity when they interact with non-specific cells. Growing evidence suggests that surface-modified exosomes have enhanced targeting capabilities and can be used as targeted drug-delivery vehicles that show promising results in the treatment of neurodegenerative diseases. In this review, we provide an up-to-date overview of existing research aimed at devising approaches to modify exosomes and elucidating their therapeutic potential in neurodegenerative diseases. Our findings indicate that exosomes can efficiently cross the blood-brain barrier to facilitate drug delivery and can also serve as early diagnostic markers for neurodegenerative diseases. We introduce the strategies being used to enhance exosome targeting, including genetic engineering, chemical modifications (both covalent, such as click chemistry and metabolic engineering, and non-covalent, such as polyvalent electrostatic and hydrophobic interactions, ligand-receptor binding, aptamer-based modifications, and the incorporation of CP05-anchored peptides), and nanomaterial modifications. Research into these strategies has confirmed that exosomes have significant therapeutic potential for neurodegenerative diseases. However, several challenges remain in the clinical application of exosomes. Improvements are needed in preparation, characterization, and optimization methods, as well as in reducing the adverse reactions associated with their use. Additionally, the range of applications and the safety of exosomes require further research and evaluation.

近年来,外泌体作为神经退行性疾病的治疗药物和早期诊断标志物得到了广泛的关注。外泌体很小,可以有效地穿过血脑屏障,使它们能够靶向深部脑病变。最近的研究表明,来自不同细胞类型的外泌体可能通过调节各种炎症细胞因子、mrna和疾病相关蛋白的表达来发挥治疗作用,从而阻止神经退行性疾病的进展,并表现出有益的作用。然而,外泌体由脂质双层膜组成,缺乏识别特定靶细胞的能力。当它们与非特异性细胞相互作用时,这种限制可能导致副作用和毒性。越来越多的证据表明,表面修饰的外泌体具有增强的靶向能力,可以用作靶向药物递送载体,在神经退行性疾病的治疗中显示出有希望的结果。在这篇综述中,我们提供了最新的现有研究概述,旨在设计修饰外泌体的方法并阐明它们在神经退行性疾病中的治疗潜力。我们的研究结果表明,外泌体可以有效地穿过血脑屏障,促进药物传递,也可以作为神经退行性疾病的早期诊断标志物。我们介绍了用于增强外胞体靶向性的策略,包括基因工程、化学修饰(包括共价修饰,如点击化学和代谢工程,以及非共价修饰,如多价静电和疏水相互作用,配体-受体结合,基于适配体的修饰,以及cp05锚定肽的结合)和纳米材料修饰。对这些策略的研究已经证实外泌体对神经退行性疾病具有显著的治疗潜力。然而,外泌体的临床应用仍然存在一些挑战。需要在制备、表征和优化方法以及减少与使用相关的不良反应方面进行改进。此外,外泌体的应用范围和安全性还需要进一步的研究和评价。
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引用次数: 0
Specific dendritic spine modifications and dendritic transport: From in vitro to in vivo. 特异性树突脊柱修饰和树突运输:从体外到体内。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-01-13 DOI: 10.4103/NRR.NRR-D-24-01159
Albert H K Fok, Charlotte H M Lam, Cora S W Lai
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引用次数: 0
Topical administration of GLP-1 eyedrops improves retinal ganglion cell function by facilitating presynaptic GABA release in early experimental diabetes. 通过促进突触前 GABA 释放,局部给药 GLP-1 眼药水可改善早期实验性糖尿病患者视网膜神经节细胞的功能。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2024-06-26 DOI: 10.4103/NRR.NRR-D-24-00001
Yu-Qi Shao, Yong-Chen Wang, Lu Wang, Hang-Ze Ruan, Yun-Feng Liu, Ti-Hui Zhang, Shi-Jun Weng, Xiong-Li Yang, Yong-Mei Zhong
<p><p>JOURNAL/nrgr/04.03/01300535-202602000-00048/figure1/v/2025-05-05T160104Z/r/image-tiff Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell loss contributing to visual dysfunction or blindness. In the brain, defects in γ-aminobutyric acid synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to retinal ganglion cells and whether and how glucagon-like peptide-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to retinal ganglion cells. In the present study, we used the patch-clamp technique to record γ-aminobutyric acid subtype A receptor-mediated miniature inhibitory postsynaptic currents in retinal ganglion cells from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic miniature inhibitory postsynaptic currents in retinal ganglion cells without altering their amplitude, suggesting a reduction in the spontaneous release of γ-aminobutyric acid to retinal ganglion cells. Topical administration of glucagon-like peptide-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of retinal ganglion cells. Concurrently, the protective effects of glucagon-like peptide-1 on retinal ganglion cells in diabetic rats were eliminated by topical administration of exendin-9-39, a specific glucagon-like peptide-1 receptor antagonist, or SR95531, a specific antagonist of the γ-aminobutyric acid subtype A receptor. Furthermore, extracellular perfusion of glucagon-like peptide-1 was found to elevate the frequencies of GABAergic miniature inhibitory postsynaptic currents in both ON- and OFF-type retinal ganglion cells. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca 2+ /protein kinase C signaling pathway downstream of glucagon-like peptide-1 receptor activation. Moreover, multielectrode array recordings revealed that glucagon-like peptide-1 functionally augmented the photoresponses of ON-type retinal ganglion cells. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of glucagon-like peptide-1. These results suggest that glucagon-like peptide-1 facilitates the release of γ-aminobutyric acid onto retinal ganglion cells through the activation of glucagon-like peptide-1 receptor, leading to the de-excitation of retinal ganglion cell circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate th
摘要:糖尿病视网膜病变是导致成人失明的一个主要原因,早期视网膜神经节细胞(RGC)缺失会导致视觉功能障碍或失明。在大脑中,Y-氨基丁酸(GABA)突触传递的缺陷与病理生理和神经退行性疾病有关,而胰高血糖素样肽-1(GLP-1)具有神经保护作用。然而,糖尿病是否会导致 RGC 抑制性输入的改变,以及 GLP-1 是否和如何通过调节 RGC 的抑制性突触传递来防止糖尿病视网膜的神经退行性病变,目前尚不清楚。在本研究中,我们利用贴片钳技术记录了链脲佐菌素诱导的糖尿病模型大鼠RGCs中GABA A亚型受体介导的微型抑制性突触后电流(mIPSCs)。我们发现,早期糖尿病(高血糖 4 周)会降低 RGC 中 GABA 能 mIPSCs 的频率,但不会改变其振幅,这表明 RGC 中 GABA 的自发释放减少了。连续两周局部注射 GLP-1 眼药水可有效对抗高血糖引起的 GABA 能 mIPSC 频率下调,从而提高 RGCs 的存活率。同时,局部注射特异性 GLP-1 受体拮抗剂 exendin-9-39 或 GABA A 亚型受体特异性拮抗剂 SR95531 可消除 GLP-1 对糖尿病大鼠 RGC 的保护作用。此外,研究还发现细胞外灌注 GLP-1 可提高 ON 型和 OFF 型 RGC 中 GABA 能 mIPSCs 的频率。研究表明,这种频率的升高是由 GLP-1 受体激活下游的磷脂酰肌醇-磷脂酶 C/1,4,5-三磷酸肌醇受体/Ca2+/蛋白激酶 C 信号通路激活介导的。此外,多电极阵列记录显示,GLP-1在功能上增强了ON型RGC的光反应。视运动反应测试表明,糖尿病大鼠的视敏度和对比敏感度下降,而局部给药 GLP-1 则可显著改善这种情况。这些结果表明,GLP-1 可通过激活 GLP-1 受体促进 GABA 在 RGC 上的释放,从而导致 RGC 环路的去兴奋化,并抑制与糖尿病视网膜病变相关的兴奋毒性过程。总之,我们的研究结果表明,GABA 系统有可能成为缓解早期糖尿病视网膜病变的治疗靶点。此外,GLP-1 眼药水的局部给药是一种非侵入性的有效治疗方法,可用于控制早期糖尿病视网膜病变。
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引用次数: 0
Sox2-overexpressing neural stem cells alleviate ventricular enlargement and neurological dysfunction in posthemorrhagic hydrocephalus. 过表达sox2的神经干细胞减轻出血性脑积水患者脑室增大和神经功能障碍。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-04-30 DOI: 10.4103/NRR.NRR-D-24-01491
Baocheng Gao, Haoxiang Wang, Shuang Hu, Kunhong Zhong, Xiaoyin Liu, Ziang Deng, Yuanyou Li, Aiping Tong, Liangxue Zhou

JOURNAL/nrgr/04.03/01300535-202602000-00045/figure1/v/2025-05-05T160104Z/r/image-tiff Neural stem cells (NSCs) have the potential for self-renewal and multidirectional differentiation, and their transplantation has achieved good efficacy in a variety of diseases. However, only 1%-10% of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus. Sox2 is an important factor for NSCs to maintain proliferation. Therefore, Sox2-overexpressing NSCs (NSCSox2) may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus. In this study, human NSCSox2 was transplanted into a posthemorrhagic hydrocephalus mouse model, and retinoic acid was administered to further promote NSC differentiation. The results showed that NSCSox2 attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function. NSCSox2 also promoted nerve regeneration, inhibited neuroinflammation and promoted M2 polarization (anti-inflammatory phenotype), thereby reducing cerebrospinal fluid secretion in choroid plexus. These findings suggest that NSCSox2 rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.

神经干细胞(Neural stem cells, NSCs)具有自我更新和多向分化的潜能,其移植治疗多种疾病已取得良好疗效。然而,只有1%-10%的移植NSCs在出血性脑积水的缺血和缺氧微环境中存活。Sox2是NSCs维持增殖的重要因子。因此,过表达sox2的NSCs (NSCSox2)可能更成功地改善出血性脑积水后的神经功能障碍。本研究将人NSCSox2移植到出血性脑积水小鼠模型中,并给予维甲酸进一步促进NSC分化。结果显示,NSCSox2可减轻出血性脑积水引起的脑室增大,改善神经功能。NSCSox2还能促进神经再生,抑制神经炎症,促进M2极化(抗炎表型),从而减少脉络膜丛脑脊液分泌。这些结果表明,NSCSox2通过神经再生和炎症调节来挽救出血性脑积水引起的脑室增大和神经功能障碍。
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引用次数: 0
Sesquiterpene lactones as potential drugs treating nerve injury. 倍半萜内酯作为治疗神经损伤的潜在药物。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2025-01-29 DOI: 10.4103/NRR.NRR-D-24-00735
Philipp Gobrecht, Marco Leibinger, Dietmar Fischer
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引用次数: 0
Neuromodulation techniques for modulating cognitive function: Enhancing stimulation precision and intervention effects. 调节认知功能的神经调节技术:提高刺激精度和干预效果。
IF 5.9 2区 医学 Q2 CELL BIOLOGY Pub Date : 2026-02-01 Epub Date: 2024-12-07 DOI: 10.4103/NRR.NRR-D-24-00836
Hanwen Cao, Li Shang, Deheng Hu, Jianbing Huang, Yu Wang, Ming Li, Yilin Song, Qianzi Yang, Yan Luo, Ying Wang, Xinxia Cai, Juntao Liu

Neuromodulation techniques effectively intervene in cognitive function, holding considerable scientific and practical value in fields such as aerospace, medicine, life sciences, and brain research. These techniques utilize electrical stimulation to directly or indirectly target specific brain regions, modulating neural activity and influencing broader brain networks, thereby regulating cognitive function. Regulating cognitive function involves an understanding of aspects such as perception, learning and memory, attention, spatial cognition, and physical function. To enhance the application of cognitive regulation in the general population, this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions. This review covers various neuromodulation techniques for cognitive intervention, including deep brain stimulation, vagus nerve stimulation, and invasive methods using microelectrode arrays. The non-invasive techniques discussed include transcranial magnetic stimulation, transcranial direct current stimulation, transcranial alternating current stimulation, transcutaneous electrical acupoint stimulation, and time interference stimulation for activating deep targets. Invasive stimulation methods, which are ideal for studying the pathogenesis of neurological diseases, tend to cause greater trauma and have been less researched in the context of cognitive function regulation. Non-invasive methods, particularly newer transcranial stimulation techniques, are gentler and more appropriate for regulating cognitive functions in the general population. These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets. This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology. It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation. Additionally, researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.

神经调节技术有效地干预认知功能,在航空航天、医学、生命科学和脑研究等领域具有相当的科学和实用价值。这些技术利用电刺激直接或间接地针对特定的大脑区域,调节神经活动并影响更广泛的大脑网络,从而调节认知功能。调节认知功能涉及对感知、学习和记忆、注意、空间认知和身体功能等方面的理解。为了加强认知调节在普通人群中的应用,本文回顾了最近发表在Web of Science上的文章,以评估有创性和非创性刺激方法在调节认知功能方面的进展和挑战。本文综述了认知干预的各种神经调节技术,包括深部脑刺激、迷走神经刺激和使用微电极阵列的侵入性方法。讨论的非侵入性技术包括经颅磁刺激、经颅直流电刺激、经颅交流电刺激、经皮穴位电刺激和激活深部目标的时间干扰刺激。有创性刺激方法是研究神经系统疾病发病机制的理想方法,但往往造成较大的创伤,在认知功能调节方面的研究较少。非侵入性方法,特别是较新的经颅刺激技术,更温和,更适合调节一般人群的认知功能。这些包括使用穴位的经皮穴位电刺激和激活深层目标的时间干扰方法。本文还讨论了神经调节技术当前的技术挑战和潜在的未来突破。建议将神经调节技术与神经检测方法相结合,以更好地评估其效果,提高无创神经调节的准确性。此外,研究闭环反馈神经调节方法被认为是未来发展的一个有希望的方向。
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引用次数: 0
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Neural Regeneration Research
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