Experimental Neurology最新文献

{"title":"Mechanisms of polygalasaponin F against brain ischemia-reperfusion injury by targeting NKCC1","authors":"Jianqi Sun ,&nbsp;Yao Sun ,&nbsp;Baohui Ma ,&nbsp;Ruifang Qi ,&nbsp;Xiaoqiong Hao ,&nbsp;Jun Lv ,&nbsp;Jinghua Shi ,&nbsp;Wei Wu ,&nbsp;Xuyang Fu ,&nbsp;Ruili Shi","doi":"10.1016/j.expneurol.2024.115076","DOIUrl":"10.1016/j.expneurol.2024.115076","url":null,"abstract":"<div><div>Stroke is a serious threat to human health and current clinical therapies remain unsatisfactory. Elevated expression of Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) following stroke can disrupt the blood-brain barrier (BBB) and result in brain edema, indicating that NKCC1 may be a potential therapeutic target for improving stroke outcomes. Polygalasaponin F (PGSF) is a triterpenoid saponin isolated from Polygala japonica Houtt, which has showed neuroprotective effects in previous studies. The present study aimed to assess the protective effects of PGSF on cerebral ischemia-reperfusion injury (CIRI) in vivo and elucidate its underlying mechanism by targeting NKCC1. Experimental results revealed that following CIRI, rats displayed neurological deficits, cerebral infarction and brain edema, concurrent with increased NKCC1 mRNA and protein expression in the cerebral tissue. Notably, the administration of PGSF at both 10 mg/kg and 20 mg/kg effectively mitigated these adverse outcomes. To explore the mechanism of PGSF, pyrosequencing was used to find that CIRI reduces the methylation of the NKCC1 promoter, while PGSF enhances it. It was thereby demonstrated that PGSF could reduce NKCC1 expression in this manner. Simultaneously, we also observed that the protein expression of DNA methyltransferase 1 (DNMT1) in the ischemic penumbra was augmented after CIRI, whereas PGSF reduced the expression of DNMT1, which was contrary to the trend of NKCC1 methylation under the treatment of PGSF. These results imply that the enhancement of NKCC1 methylation by PGSF may not be catalyzed by DNMT1 and that the reduction of NKCC1 methylation level after CIRI may not be related to DNMT1. Finally, we discovered that PGSF can decrease the leakage of the BBB and enhance the expression of the BBB structural proteins occludin and ZO-1. In conclusion, PGSF can target NKCC1 as an epigenetic target and downregulate its expression following CIRI by enhancing DNA methylation of NKCC1, thereby safeguarding the structure and function of brain tissue.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115076"},"PeriodicalIF":4.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750506","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":"Docosahexaenoic acid protects against ischemic stroke in diabetic mice by inhibiting inflammatory responses and apoptosis","authors":"Cuiying Liu ,&nbsp;Jiayi Guo ,&nbsp;Longfei Guan ,&nbsp;Chenyang Li ,&nbsp;Xiaoyan Hu ,&nbsp;Xinchun Jin ,&nbsp;Baohui Xu ,&nbsp;Junfa Li ,&nbsp;Heng Zhao","doi":"10.1016/j.expneurol.2024.115075","DOIUrl":"10.1016/j.expneurol.2024.115075","url":null,"abstract":"<div><div>This study was to explore whether docosahexaenoic acid (DHA) protects against ischemic stroke in diabetic mice and its mechanisms. DHA was administered to mice and its effects on stroke outcomes in type 1 diabetes mellitus were assessed 24 h and 3 days post-reperfusion using RNA sequencing, flow cytometry, multiplex immunoassays, and western-blotting analysis. In diabetic mice, DHA administration post-ischemic stroke significantly reduced cerebral infarct size, brain edema, and neurological impairments. Flow cytometric analysis demonstrated a notable decrease in the percentage of neutrophils in the ischemic brain, suggesting a mitigated inflammatory response. Western blotting assay revealed that pro-apoptotic protein Bax was reduced whereas anti-apoptotic protein Bcl-2 was increased, indicating the attenuation of apoptosis. Additionally, RNA sequencing of brain tissue highlighted significant transcriptomic changes, with downregulation of genes for several inflammatory pathways such as NF-kappa B signaling and upregulation of genes for neuroprotective pathways such as neuroactive ligand-receptor interaction. Similar transcriptomic changes in peripheral blood mononuclear cells indicated that DHA treatment resulted the systemic anti-inflammatory and neuroprotective response. DHA treatment mitigated cerebral ischemic injuries by dampening inflammatory responses and apoptosis in diabetic mice after ischemic stroke, highlighting its therapeutic potential for clinical management of stroke in diabetic patients.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115075"},"PeriodicalIF":4.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750505","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":"PGAM5 promotes RIPK1-PANoptosome activity by phosphorylating and activating RIPK1 to mediate PANoptosis after subarachnoid hemorrhage in rats","authors":"Jiajia Duan ,&nbsp;Wen Yuan ,&nbsp;Enyan Jiang ,&nbsp;Xiaojian Zhang ,&nbsp;Zhen Fang ,&nbsp;Jia Zeng ,&nbsp;Jikai Wang ,&nbsp;Xiaoxin Yan ,&nbsp;Aihua Liu ,&nbsp;Fangen Kong ,&nbsp;Fei Liu","doi":"10.1016/j.expneurol.2024.115072","DOIUrl":"10.1016/j.expneurol.2024.115072","url":null,"abstract":"<div><div>Neuronal death plays a crucial role in early brain injury after subarachnoid hemorrhage (SAH). PANoptosis is a programmed form of cell death regulated by the PANoptosome, which possesses key characteristics of pyroptosis, apoptosis and necroptosis. Phosphoglycerate mutase family member 5 (PGAM5) has specific phosphatase activity that phosphorylates or dephosphorylates serine and threonine residues on bound proteins such as receptor-interacting protein kinase 1 (RIPK1), which are involved in programmed cell death. This study aimed to explore whether PANoptosis occurs after subarachnoid hemorrhage and to investigate the role of PGAM5 in early brain injury after SAH. A monofilament perforation SAH model in Sprague–Dawley rats was established, and PGAM5 siRNA (siPGAM5) was administered via intracerebroventricular injection 48 h before SAH modeling. The efficacy of siPGAM5 treatment was assessed via neurological scoring, and the impact of siPGAM5 on PANoptosis was evaluated via Western blotting, TUNEL staining and ELISA. To investigate its potential mechanism, the RIPK1 activator birinapant was administered intraperitoneally 0.5 h after SAH. The role of RIPK in PGAM5-mediated PANoptosis was evaluated by Western blotting and coimmunoprecipitation. Our findings indicate that PANoptosis occurs in neurons after SAH and that reducing PGAM5 in the cytosol after SAH can reduce PANoptosis and enhance the short-term and long-term neurological functions of SAH rats. Mechanistically, we discovered that PGAM5 can directly bind to and phosphorylate and activate RIPK1 (ser 166), triggering the assembly of the RIPK1-PANoptosome complex. In conclusion, our study revealed that the increased PGAM5 in the mitochondria-free cytosol after SAH can bind to and activate RIPK1 (ser 166), driving the assembly of the RIPK1-PANoptosome and mediating PANoptosis after SAH. PGAM5 and PANoptosis might be novel therapeutic targets for SAH.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115072"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738934","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":"The role of kynurenine pathway metabolism mediated by exercise in the microbial-gut-brain axis in Alzheimer's disease","authors":"Yiyang Wang ,&nbsp;Weijia Wu ,&nbsp;Fanqi Zeng ,&nbsp;Xiangyuan Meng ,&nbsp;Mei Peng ,&nbsp;Juan Wang ,&nbsp;Zeyu Chen ,&nbsp;Wenfeng Liu","doi":"10.1016/j.expneurol.2024.115070","DOIUrl":"10.1016/j.expneurol.2024.115070","url":null,"abstract":"<div><div>In recent years, the role of the microbiome–gut–brain axis in the pathogenesis of Alzheimer's disease (AD) has garnered increasing attention. Specifically, tryptophan metabolism via the kynurenine pathway (KP) plays a crucial regulatory role in this axis. This study reviews how exercise regulates the microbiome–gut–brain axis by influencing kynurenine pathway metabolism, thereby exerting resistance against AD. This paper also discusses how exercise positively impacts AD via the microbiome–gut–brain axis by modulating the endocrine, autonomic nervous, and immune systems. Although the specific mechanisms are not fully understood, research indicates that exercise may optimize tryptophan metabolism by promoting the growth of beneficial microbiota and inhibiting harmful microbiota, producing substances that are beneficial to the nervous system and combating AD. The aim of this review is to provide new perspectives and potential intervention strategies for the prevention and treatment of AD by exploring the links between exercise, KP and the gut-brain axis.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115070"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738936","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":"Two cardinal features of ALS, reduced STMN2 and pathogenic TDP-43, synergize to accelerate motor decline in mice","authors":"Kelsey L. Krus ,&nbsp;Ana Morales Benitez ,&nbsp;Amy Strickland ,&nbsp;Jeffrey Milbrandt ,&nbsp;A. Joseph Bloom ,&nbsp;Aaron DiAntonio","doi":"10.1016/j.expneurol.2024.115068","DOIUrl":"10.1016/j.expneurol.2024.115068","url":null,"abstract":"<div><div>Pathological TDP-43 loss from the nucleus and cytoplasmic aggregation occurs in almost all cases of ALS and half of frontotemporal dementia patients. <em>Stathmin2</em> (<em>Stmn2)</em> is a key target of TDP-43 regulation and aberrantly spliced <em>Stmn2</em> mRNA is found in patients with ALS, frontotemporal dementia, and Alzheimer's Disease. STMN2 participates in the axon injury response and its depletion <em>in vivo</em> partially replicates ALS-like symptoms including progressive motor deficits and distal NMJ denervation. The interaction between STMN2 loss and TDP-43 dysfunction has not been studied in mice because TDP-43 regulates human but not murine <em>Stmn2</em> splicing. Therefore, we generated trans-heterozygous mice that lack one functional copy of <em>Stmn2</em> and express one mutant TDP-43^Q331K knock-in allele to investigate whether reduced STMN2 function exacerbates TDP-43-dependent pathology. Indeed, we observe synergy between these two alleles, resulting in an early onset, progressive motor deficit. Surprisingly, this behavioral defect is not accompanied by detectable neuropathology in the brain, spinal cord, peripheral nerves or at neuromuscular junctions (NMJs). However, the trans-heterozygous mice exhibit abnormal mitochondrial morphology in their distal axons and NMJs. As both STMN2 and TDP-43 affect mitochondrial dynamics, and neuronal mitochondrial dysfunction is a cardinal feature of many neurodegenerative diseases, this abnormality likely contributes to the observed motor deficit. These findings demonstrate that partial loss of STMN2 significantly exacerbates TDP-43-associated phenotypes, suggesting that STMN2 restoration could ameliorate TDP-43 related disease before the onset of degeneration.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115068"},"PeriodicalIF":4.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease registries and rare disorders: The virtuous example of mitochondrial medicine","authors":"Daniele Orsucci ,&nbsp;Elena Caldarazzo Ienco ,&nbsp;Piervito Lopriore ,&nbsp;Michelangelo Mancuso","doi":"10.1016/j.expneurol.2024.115073","DOIUrl":"10.1016/j.expneurol.2024.115073","url":null,"abstract":"<div><div>Primary mitochondrial disorders (PMDs) are an extraordinarily complex group of rare disorders caused by impairment of the mitochondrial electron transport chain, or respiratory chain. Studying genotype-phenotype relationships in PMDs is a complex task. The clinical variability is large even in individuals with the same genotype, and the statistical power is low in single-center studies because of their rarity. To better define the clinical phenotypes associated with PMDs, in the last 15 years a significant multicenter effort has led to nation-wide studies on large cohorts of patients. Many national registries of mitochondrial patients have been developed in recent years, and now there is a strong effort towards international (and even global) registries. This review will revise the notable advances obtained with such studies in recent years, and will discuss the actual developments and future perspectives.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115073"},"PeriodicalIF":4.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738920","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":"The emerging role of the microglia triggering receptor expressed on myeloid cells (TREM) 2 in multiple sclerosis","authors":"Mahan Farzan ,&nbsp;Masoumeh Saberi-Rounkian ,&nbsp;Atefeh Asadi-Rizi ,&nbsp;Zahra Heidari ,&nbsp;Mahour Farzan ,&nbsp;Mobina Fathi ,&nbsp;Ava Aghaei ,&nbsp;Fatemeh Azadegan-Dehkordi ,&nbsp;Nader Bagheri","doi":"10.1016/j.expneurol.2024.115071","DOIUrl":"10.1016/j.expneurol.2024.115071","url":null,"abstract":"<div><h3>Background</h3><div>The chronic inflammatory condition known as multiple sclerosis (MS) causes inflammation and demyelination in the central nervous system (CNS). The activation of multiple cell types, including the CNS's resident immune cells called microglia, is a component of the immunological response in MS. Recently, the triggering receptor expressed on myeloid cells (TREM) family has emerged as a crucial player in modulating microglial function and subsequent neuroinflammation. Understanding the role of TREM receptors in MS pathogenesis could provide insightful information on how to develop new therapeutic approaches.</div></div><div><h3>Main body</h3><div>The TREM family consists of several receptors, including TREM-1 and TREM-2, which can be expressed on both immune cells, such as myeloid cells and microglia, and non-immune cells. These receptors interact with their respective ligands and regulate signaling pathways, ultimately leading to the control of microglial activation and inflammatory reactions. TREM-2, in particular, has garnered significant interest because of its connection with MS and other neurodegenerative diseases. The activation of microglia through TREM receptors in MS is thought to influence the equilibrium between helpful and detrimental inflammatory responses. TREM receptors can promote the phagocytosis of myelin debris and remove apoptotic cells, thus contributing to tissue repair and regeneration. However, excessive or dysregulated activation of microglia mediated by TREM receptors can lead to the release of pro-inflammatory cytokines and neurotoxic factors, exacerbating neuroinflammation and neurodegeneration in MS.</div></div><div><h3>Conclusion</h3><div>The emerging role of the TREM family in demyelinating diseases highlights the importance of microglia in disease pathogenesis. Understanding the mechanisms by which TREM receptors modulate microglial function can provide valuable insights into the development of targeted therapies for these disorders. By selectively targeting TREM receptors, it may be possible to harness their beneficial effects on tissue repair while dampening their detrimental pro-inflammatory responses. Further research is warranted to elucidate the precise signaling pathways and ligand interactions involved in TREM-mediated microglial activation, which could uncover novel therapeutic avenues for treating MS and other neuroinflammatory disorders.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115071"},"PeriodicalIF":4.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715881","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":"Schwann cell transplantation for remyelination, regeneration, tissue sparing, and functional recovery in spinal cord injury: A systematic review and meta-analysis of animal studies","authors":"Pooya Hajimirzaei ,&nbsp;Faeze Sadat Ahmadi Tabatabaei ,&nbsp;Hamed Nasibi-Sis ,&nbsp;Reyhane Sadat Razavian ,&nbsp;Farinaz Nasirinezhad","doi":"10.1016/j.expneurol.2024.115062","DOIUrl":"10.1016/j.expneurol.2024.115062","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal cord injury (SCI) is a significant global health challenge that results in profound physical and neurological impairments. Despite progress in medical care, the treatment options for SCI are still restricted and often focus on symptom management rather than promoting neural repair and functional recovery. This study focused on clarifying the impact of Schwann cell (SC) transplantation on the molecular, cellular, and functional basis of recovery in animal models of SCI.</div></div><div><h3>Material and methods</h3><div>Relevant studies were identified by conducting searches across multiple databases, which included PubMed, Web of Science, Scopus, and ProQuest. The data were analyzed via comprehensive meta-analysis software. We assessed the risk of bias via the SYRCLE method.</div></div><div><h3>Results</h3><div>The analysis included 59 studies, 48 of which provided quantitative data. The results revealed significant improvements in various outcome variables, including protein zero structures (SMD = 1.66, 95 %CI: 0.96–2.36; <em>p</em> &lt; 0.001; I² = 49.8 %), peripherally myelinated axons (SMD = 1.81, 95 %CI: 0.99–2.63; p &lt; 0.001; I² = 39.3 %), biotinylated dextran amine-labeled CST only rostral (SMD = 1.31, 95 % CI: 0.50–2.12, <em>p</em> &lt; 0.01, I² = 49.7 %), fast blue-labeled reticular formation (SMD = 0.96, 95 %CI: 0.43–1.49, <em>p</em> &lt; 0.001, I² = 0.0 %), 5-hydroxytryptamine caudally (SMD = 0.83, 95 %CI: 0.36–1.29, <em>p</em> &lt; 0.001, I² = 17.2 %) and epicenter (SMD = 0.85, 95 %CI: 0.17–1.53, <em>p</em> &lt; 0.05, I² = 62.7 %), tyrosine hydroxylase caudally (SMD = 1.86, 95 %CI: 1.14–2.59, <em>p</em> &lt; 0.001, I² = 0.0 %) and epicenter (SMD = 1.82, 95 %CI: 1.18–2.47, p &lt; 0.001, I² = 0.0 %), cavity volume (SMD = −2.07, 95 %CI: −2.90 - −1.24, p &lt; 0.001, I² = 67.2 %), and Basso, Beattie, and Bresnahan (SMD = 1.26, 95 %CI: 0.93–1.58; p &lt; 0.001; I² = 79.4 %).</div></div><div><h3>Conclusions</h3><div>This study demonstrates the promising potential of SC transplantation as a therapeutic approach for SCI, clarifying its impact on various biological processes critical for recovery.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115062"},"PeriodicalIF":4.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695351","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":"Preferential motor reinnervation is modulated by both repair site and distal nerve environments","authors":"C. Li ,&nbsp;N. Rassekh ,&nbsp;A. O'Daly ,&nbsp;F. Kebaisch ,&nbsp;R. Wolinsky ,&nbsp;A. Vyas ,&nbsp;R. Skolasky ,&nbsp;A. Hoke ,&nbsp;T. Brushart","doi":"10.1016/j.expneurol.2024.115066","DOIUrl":"10.1016/j.expneurol.2024.115066","url":null,"abstract":"<div><div>To restore function after nerve injury, axons must regenerate from the injury site to the periphery, then reinnervate appropriate end organs when they arrive. Only 10 % of adults who suffer nerve injury will regain normal function, often because axons regenerate to functionally inappropriate targets (<span><span>Brushart, 2011</span></span>). The peripheral destination of these axons is largely determined by the pathways they enter at the site of nerve repair. To improve clinical outcomes, it is thus critical to improve the accuracy of axon pathfinding. In rodents, motor axons regenerating in mixed nerve preferentially reinnervate pathways leading to muscle, a process termed preferential motor reinnervation (PMR). Previous experiments have shown that PMR can be enhanced by predegenerating nerve grafts to enhance growth factor production and remove inhibitory factors (<span><span>Abdullah et al., 2013</span></span>). The current experiments explore the relative contributions of motor pathways, sensory pathways, and the repair environment to this enhancement. Sensory and/or motor pathways within rat femoral nerve grafts were predegenerated for 3 weeks to optimize growth factor production (<span><span>Brushart et al., 2013</span></span>) or for 12 weeks to deplete it. Optimizing the environment within previously motor Schwann cell tubes promoted PMR, regardless of whether adjacent sensory pathways were optimized or chronically denervated. However, this positive effect was abolished when sensory pathways were undergoing acute Wallerian degeneration immediately after nerve repair. The repair environment thus precluded motor axon pathfinding in spite of an optimized distal motor pathway. When sensory pathways were optimized and motor pathways were chronically denervated, not only was PMR abolished, but motoneurons failed to respond to the greater volume of growth factors in the sensory nerve. Small sensory neurons, however, selectively reinnervated cutaneous nerve under these conditions. These experiments thus strengthen the concept that, in adult rats, sensory and motor pathways have unique identities capable of influencing both sensory and motor axon regeneration. Furthermore, they demonstrate that, in the rat, delaying nerve repair for 3 weeks to enhance growth factor production and clear the products of acute Wallerian degeneration can enhance regeneration specificity without the need for exogenous treatments.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"385 ","pages":"Article 115066"},"PeriodicalIF":4.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695328","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":"Enhancing cognitive function after traumatic brain injury in male mice: The benefits of running regardless of intervention timing","authors":"Liron Tseitlin ,&nbsp;Shaul Schreiber ,&nbsp;Bar Richmond-Hacham ,&nbsp;Lior Bikovski ,&nbsp;Chaim G. Pick","doi":"10.1016/j.expneurol.2024.115069","DOIUrl":"10.1016/j.expneurol.2024.115069","url":null,"abstract":"<div><div>The significant benefits of physical activity are well-documented in academic literature, with growing evidence highlighting its positive effects (among others) on memory and cognitive function. Exercise, particularly aerobic activities, has been shown to mitigate neuroinflammatory processes, promote neuronal regeneration, facilitate recovery from cerebral trauma, and reduce the risk of neurodegenerative diseases. Among neurological conditions, traumatic brain injury (TBI) is the most common in individuals under 50, with 80–90 % of cases categorized as mild traumatic brain injury (mTBI).</div><div>This study investigates the impact of exercise on visual and spatial memory deficits in mice following mTBI. ICR mice were subjected to a seventeen-day treadmill training protocol initiated at four different time intervals post-mTBI (2, 7, 13, and 30 days). A battery of specific behavioral tests was used to assess anxiety-like behaviors, motor skills, and visual and spatial memory.</div><div>Our results indicate that running positively affected mTBI in both novel object recognition (<em>p</em> &lt; 0.001) and Y-maze (p &lt; 0.001) regardless of the running protocol's initiation time, demonstrating that aerobic exercise significantly alleviates cognitive deficits associated with mTBI. Importantly, mTBI did not appear to impact motor abilities or anxiety-like behaviors based on the assessment paradigms utilized. In conclusion, aerobic exercise effectively enhances visual and spatial memory post-mTBI, with promising results observed even when the running protocol is initiated up to one-month post-injury.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":"384 ","pages":"Article 115069"},"PeriodicalIF":4.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692854","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}