Tassilo Jungenitz, Lukas Frey, Sophia Kirscht, Stephan W Schwarzacher, Angélica Zepeda
{"title":"Hippocampal damage through foreign body placement in organotypic cultures leads to plastic responses in newly born granule cells.","authors":"Tassilo Jungenitz, Lukas Frey, Sophia Kirscht, Stephan W Schwarzacher, Angélica Zepeda","doi":"10.4103/NRR.NRR-D-24-00783","DOIUrl":"10.4103/NRR.NRR-D-24-00783","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202603000-00038/figure1/v/2025-06-16T082406Z/r/image-tiff The dentate gyrus of the hippocampus is a plastic structure that displays modifications at different levels in response to positive stimuli as well as to negative conditions such as brain damage. The latter involves global alterations, making understanding plastic responses triggered by local damage difficult. One key feature of the dentate gyrus is that it contains a well-defined neurogenic niche, the subgranular zone, and beyond neurogenesis, newly born granule cells may maintain a \"young\" phenotype throughout life, adding to the plastic nature of the structure. Here, we present a novel experimental model of local brain damage in organotypic entorhino-hippocampal cultures that results in the activation of adjacent newly born granule cells. A small piece of filter paper was placed on the surface of the granule cell layer of the dentate gyrus, which evoked a foreign body reaction of astrocytes, along with the activation of local young neurons expressing doublecortin. Forty-eight hours after foreign body placement, the number of doublecortin-immunoreactive cells increased in the subgranular zone in the direct vicinity of the foreign body, whereas overall increased doublecortin immunoreactivity was observed in the granule cell layer and molecular layer of the dentate gyrus. Foreign body placement in the pyramidal layer of the CA1 region evoked a comparable local astroglial reaction but did not lead to an increase in doublecortin-immunoreactive in either the CA1 region or the adjacent dentate gyrus. Seven days after foreign body placement in the dentate gyrus, the increase in doublecortin-immunoreactivity was no longer observed, indicating the transient activation of young cells. However, 7 days after foreign body placement, the number of doublecortin-immunoreactive granule cells coimmunoreactive for calbindin was lower than that under the control conditions. As calbindin is a marker for mature granule cells, this result suggests that activated young cells remain at a more immature stage following foreign body placement. Live imaging of retrovirally green fluorescent protein-labeled newly born granule cells revealed the orientation and growth of their dendrites toward the foreign body placement. This novel experimental model of foreign body placement in organotypic entorhino-hippocampal cultures could serve as a valuable tool for studying both glial reactivity and neuronal plasticity, specifically of newly born neurons under controlled in vitro conditions.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1142-1150"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Secretory autophagy in neurons: More than throwing out the trash?","authors":"Alexander Veh, Patrick Lüningschrör","doi":"10.4103/NRR.NRR-D-24-01514","DOIUrl":"10.4103/NRR.NRR-D-24-01514","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1108-1109"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astrocyte glycolysis in Alzheimer's disease: When the stars burn out.","authors":"Simon M Bell, Heather Mortiboys","doi":"10.4103/NRR.NRR-D-24-01519","DOIUrl":"10.4103/NRR.NRR-D-24-01519","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1130-1131"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingxiu Li, Keyuan Gao, Lili Wang, Jiayue Wang, Mian Qin, Xinrui Wang, Kai Lian, Chao Li, Shan'e Gao, Chenxi Sun
{"title":"Astrocytes: Therapeutic targets for stroke.","authors":"Jingxiu Li, Keyuan Gao, Lili Wang, Jiayue Wang, Mian Qin, Xinrui Wang, Kai Lian, Chao Li, Shan'e Gao, Chenxi Sun","doi":"10.4103/NRR.NRR-D-24-01062","DOIUrl":"10.4103/NRR.NRR-D-24-01062","url":null,"abstract":"<p><p>Stroke is the leading cause of mortality globally, ultimately leading to severe, lifelong neurological impairments. Patients often suffer from a secondary cascade of damage, including neuroinflammation, cytotoxicity, oxidative stress, and mitochondrial dysfunction. Regrettably, there is a paucity of clinically available therapeutics to address these issues. Emerging evidence underscores the pivotal roles of astrocytes, the most abundant glial cells in the brain, throughout the various stages of ischemic stroke. In this comprehensive review, we initially provide an overview of the fundamental physiological functions of astrocytes in the brain, emphasizing their critical role in modulating neuronal homeostasis, synaptic activity, and blood-brain barrier integrity. We then delve into the growing body of evidence that highlights the functional diversity and heterogeneity of astrocytes in the context of ischemic stroke. Their well-established contributions to energy provision, metabolic regulation, and neurotransmitter homeostasis, as well as their emerging roles in mitochondrial recovery, neuroinflammation regulation, and oxidative stress modulation following ischemic injury, are discussed in detail. We also explore the cellular and molecular mechanisms underpinning these functions, with particular emphasis on recently identified targets within astrocytes that offer promising prospects for therapeutic intervention. In the final section of this review, we offer a detailed overview of the current therapeutic strategies targeting astrocytes in the treatment of ischemic stroke. These astrocyte-targeting strategies are categorized into traditional small-molecule drugs, microRNAs (miRNAs), stem cell-based therapies, cellular reprogramming, hydrogels, and extracellular vesicles. By summarizing the current understanding of astrocyte functions and therapeutic targeting approaches, we aim to highlight the critical roles of astrocytes during and after stroke, particularly in the pathophysiological development in ischemic stroke. We also emphasize promising avenues for novel, astrocyte-targeted therapeutics that could become clinically available options, ultimately improving outcomes for patients with stroke.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1074-1088"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synapses and dendritic spines are eliminated in the primary visual cortex of mice subjected to chronic intraocular pressure elevation.","authors":"Xinyi Zhang, Deling Li, Weiting Zeng, Yiru Huang, Zongyi Zhan, Yuning Zhang, Qinyuan Hu, Lianyan Huang, Minbin Yu","doi":"10.4103/NRR.NRR-D-24-00394","DOIUrl":"10.4103/NRR.NRR-D-24-00394","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202603000-00046/figure1/v/2025-06-16T082406Z/r/image-tiff Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease. Glaucoma directly impairs retinal ganglion cells and their axons, leading to axonal transport dysfuntion, subsequently causing secondary damage to anterior or posterior ends of the visual system. Accordingly, recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway. However, the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear. In this study, we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye. We found that, after 4 weeks of chronic ocular hypertension, the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye. This was accompanied by glial cell activation and increased expression of inflammatory factors. After 8 weeks of ocular hypertension, we observed a reduction in the number of excitatory and inhibitory synapses, dendritic spines, and activation of glial cells in the primary visual cortex contralateral to the affected eye. These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex, providing new insights into the pathogenesis of glaucoma.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1236-1248"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Li, Jianquan Liu, Liuxun Li, Guotian Luo, Xinrong Yuan, Shichao Shen, Yongpeng Shi, Jianlong Wu, Bin Yan, Lei Yang
{"title":"Porcine decellularized nerve matrix hydrogel attenuates neuroinflammation after peripheral nerve injury by inhibiting the TLR4/MyD88/NF-κB axis.","authors":"Rui Li, Jianquan Liu, Liuxun Li, Guotian Luo, Xinrong Yuan, Shichao Shen, Yongpeng Shi, Jianlong Wu, Bin Yan, Lei Yang","doi":"10.4103/NRR.NRR-D-24-00302","DOIUrl":"10.4103/NRR.NRR-D-24-00302","url":null,"abstract":"<p><p>JOURNAL/nrgr/04.03/01300535-202603000-00045/figure1/v/2025-06-16T082406Z/r/image-tiff Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge. Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity, highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury; however, its role in modulating neuroinflammation post-peripheral nerve injury remains unknown. Here, we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms. Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel, we evaluated structural and functional recovery, macrophage phenotype alteration, specific cytokine expression, and changes in related signaling molecules in vivo . Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium. These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages. Additionally, porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro . Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway, providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.</p>","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1222-1235"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Somatostatin interneurons and the pathogenesis of Alzheimer's disease.","authors":"Victor N Almeida, Guilherme S V Higa","doi":"10.4103/NRR.NRR-D-24-01277","DOIUrl":"10.4103/NRR.NRR-D-24-01277","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":" ","pages":"1128-1129"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Are emerging electroconductive biomaterials for spinal cord injury repair the future?","authors":"Aleksandra Serafin, Maurice N Collins","doi":"10.4103/NRR.NRR-D-24-01074","DOIUrl":"https://doi.org/10.4103/NRR.NRR-D-24-01074","url":null,"abstract":"","PeriodicalId":19113,"journal":{"name":"Neural Regeneration Research","volume":"21 3","pages":"1140-1141"},"PeriodicalIF":5.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}