Xuejia Liu , Zhisheng Han , Yuming Huang , Mingzhi Li , Jialu Tian , Shan Zhao , Yonghai Li , Juntang Lin , Han Li
{"title":"HIF1α/SLC7A11 signaling attenuates 6-hydroxydopamine-induced ferroptosis in animal and cell models of Parkinson’s disease","authors":"Xuejia Liu , Zhisheng Han , Yuming Huang , Mingzhi Li , Jialu Tian , Shan Zhao , Yonghai Li , Juntang Lin , Han Li","doi":"10.1016/j.jnrt.2024.100171","DOIUrl":"10.1016/j.jnrt.2024.100171","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of Parkinson’s disease (PD) is associated with ferroptosis. The role of HIF1α is involved in several diseases, but its specific function in PD remains uncertain.</div></div><div><h3>Methods</h3><div>In this study, we generated animal and cellular models of PD using the neurotoxin 6-OHDA. The occurrence of ferroptosis was determined by measuring levels of ferroptosis-related proteins, Fe<sup>2+</sup> amount and transmission electron microscopy analysis in the PD models, and was further confirmed by using a ferroptosis inhibitor. HIF1α overexpressing and HIF1α knockdown SH-SY5Y cells were constructed by lentivirus transfection. Then, the levels of lipid peroxide, ROS, SLC7A11, and GPX4 were detected to elucidate the relationship between HIF1α and ferroptosis. Luciferase assay was used to analyze the regulation between HIF1α and SLC7A11.</div></div><div><h3>Results</h3><div>We observed a significant downregulation of HIF1α in both animal and cellular PD models. Overexpression of HIF1α mitigated 6-OHDA-induced ferroptosis in SH-SY5Y cells, while, conversely, downregulation of HIF1α promoted ferroptosis in SH-SY5Y cells. BioEdit Sequence Alignment Editor software identified a hypoxia response element (HRE) within the promoter sequence of <em>SLC7A11</em>. The dual-luciferase reporter assays demonstrated that the co-expression of HIF1α and the <em>SLC7A11</em> promoter significantly augmented reporter activity in SH-SY5Y cells. Moreover, introduction of a mutation into the HRE of the <em>SLC7A11</em> promoter abolished the induction of SLC7A11 by HIF1α overexpression, resulted in a reduction in promoter activity compared with wild-type cells.</div></div><div><h3>Conclusions</h3><div>The collective findings of this study indicate that HIF1α can inhibit ferroptosis by positively regulating <em>SLC7A11</em>. This investigation has shed light on the crucial involvement of the HIF1α/SLC7A11 signaling axis in ferroptosis in PD models, thereby presenting patients with PD a promising therapeutic target.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 1","pages":"Article 100171"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongyun Huang, Paul R. Sanberg, Hari Shanker Sharma, Sang Ryong Jeon
{"title":"The responsibility and mission of Neurorestoratology‒New year’s greetings for 2025","authors":"Hongyun Huang, Paul R. Sanberg, Hari Shanker Sharma, Sang Ryong Jeon","doi":"10.1016/j.jnrt.2024.100174","DOIUrl":"10.1016/j.jnrt.2024.100174","url":null,"abstract":"","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 1","pages":"Article 100174"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primed low frequency repetitive transcranial magnetic stimulation rebalances cortical excitatory-inhibitory circuitry and improves functional outcomes in infantile cerebral palsy patients: A randomized controlled trial","authors":"Aliya Mufti , Suman Jain , Kanwal Preet Kochhar , Sheffali Gulati , Sanjay Wadhwa , Kapil Sikka , Rohit Saxena , Md Iqbal Alam","doi":"10.1016/j.jnrt.2024.100169","DOIUrl":"10.1016/j.jnrt.2024.100169","url":null,"abstract":"<div><h3>Background</h3><div>Multiple prenatal and postnatal etiologies in cerebral palsy (CP) patients cause neural tissue damage and alterations in cortical neuronal activity and plasticity, leading to motor and cognitive deficits early in life. Repetitive transcranial magnetic stimulation (rTMS) to the lesioned or contralesional hemisphere has been shown to alleviate these functional deficits. However, the underlying mechanisms of the beneficial effects of rTMS via realigning intracortical and interhemispheric circuitry and excitability remain unclear. The present study explored the ability of primed low-frequency rTMS to modulate intracortical excitatory-inhibitory circuitry, interhemispheric and corticospinal integrity, and plasticity in infantile hemiplegic CP.</div></div><div><h3>Methods</h3><div>The current study was a randomized, placebo-controlled trial with infantile hemiplegic CP patients. The active group received 6 Hz primed low-frequency 1Hz rTMS delivered to the contralesional primary motor cortex for 4 weeks, in 10 sessions. The placebo group received sham stimulation. Both groups also underwent 10 sessions of modified-constraint induced movement therapy (mCIMT). Pre- and post-intervention assessments were conducted using the Quality of Upper Extremity Skills Test to evaluate sensory and motor function, and the Modified Ashworth Scale (MAS) to assess spasticity. Additionally, cortical excitability and plasticity were measured using single- and paired-pulse TMS.</div></div><div><h3>Results</h3><div>We found a significant increase in Quality of Upper Extremity Skills Test scores, CP Quality of Life Child (CP QOL-Child) scores, and grip strength, and a decrease in MAS scores in the active rTMS group compared with the sham group. Single- and paired-pulse paradigms revealed a significant decrease in resting and active motor threshold, a reduction in the cortical silent period, and short- and long-interval intracortical inhibition in the intervention group compared with the sham group.</div></div><div><h3>Conclusion</h3><div>Primed low-frequency rTMS in the contralesional hemisphere combined with mCIMT shows potential for modulating motor neuronal excitability, rebalancing intracortical excitatory-inhibitory circuitry, and enhancing functional outcomes in children with infantile hemiparetic CP.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 1","pages":"Article 100169"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Top cited articles of 2023 in Journal of Neurorestoratology","authors":"Yong Hu","doi":"10.1016/j.jnrt.2024.100172","DOIUrl":"10.1016/j.jnrt.2024.100172","url":null,"abstract":"","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 1","pages":"Article 100172"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143169756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Weihong Wang , Qiang Tang , Hua Liu , Rong Xu , Lijun Zhang
{"title":"Timing of single-event multilevel surgical interventions on long-term motor outcomes in children and adolescents with cerebral palsy: A systematic review and meta-analysis","authors":"Weihong Wang , Qiang Tang , Hua Liu , Rong Xu , Lijun Zhang","doi":"10.1016/j.jnrt.2024.100170","DOIUrl":"10.1016/j.jnrt.2024.100170","url":null,"abstract":"<div><h3>Background</h3><div>The aim of this meta-analysis was to evaluate the impact of the timing of single-event multilevel surgery (SEMLS) on long-term motor outcomes in children and adolescents with cerebral palsy (CP).</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis were conducted by searching PubMed, Cochrane Library, Embase, and Web of Science databases for studies up to April 2024. Twelve eligible studies were included, from which we examined patients’ gait, stride length, walking speed, and the gross motor function measure (GMFM66).</div></div><div><h3>Results</h3><div>Gait analysis showed significant improvements in CP patients after SEMLS, which included an increased gait deviation index (<em>p</em> < 0.001), reduced Gillette gait index (<em>p</em> < 0.001), and reduced gait profile score (<em>p</em> < 0.001). Subgroup analysis showed that age at surgery (<12 years old vs. 12−18 years old) was not a factor affecting patients’ gait. Spatial and temporal parameters such as stride length (<em>p</em> < 0.001) and walking velocity (<em>p</em> = 0.02) also improved significantly after surgery. However, there were only trends towards broader motor function gains measured by the GMFM66 (<em>p</em> = 0.39).</div></div><div><h3>Conclusions</h3><div>SEMLS effectively improved key gait and mobility parameters in children and adolescents with CP, and was not affected by younger or older surgical ages (<12 years old or 12−18 years old). However, these gait improvements do not uniformly translate into broader motor function gains.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 1","pages":"Article 100170"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143170166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongyun Huang , Paul R. Sanberg , Hari Shanker Sharma , Sang Ryong Jeon
{"title":"Developmental phases of Neurorestoratology and current key tasks","authors":"Hongyun Huang , Paul R. Sanberg , Hari Shanker Sharma , Sang Ryong Jeon","doi":"10.1016/j.jnrt.2025.100189","DOIUrl":"10.1016/j.jnrt.2025.100189","url":null,"abstract":"","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 2","pages":"Article 100189"},"PeriodicalIF":3.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renke He , Jiayu Liu , Bingxian Wang , Hanbo Zhang , Shengqiang Xie , Yiyuan Zhang , Xianhong Liu , Jianxin Wang , Dai Wu , Lehui Du , Baolin Qu , Gang Cheng , Jianning Zhang
{"title":"X-ray-based ultra-high dose rate FLASH radiotherapy mitigates acute radiation-induced hippocampal injury and inflammation","authors":"Renke He , Jiayu Liu , Bingxian Wang , Hanbo Zhang , Shengqiang Xie , Yiyuan Zhang , Xianhong Liu , Jianxin Wang , Dai Wu , Lehui Du , Baolin Qu , Gang Cheng , Jianning Zhang","doi":"10.1016/j.jnrt.2025.100186","DOIUrl":"10.1016/j.jnrt.2025.100186","url":null,"abstract":"<div><h3>Background</h3><div>To compare neural damage induced by ultra-high dose rate FLASH radiotherapy (FLASH-RT) with that induced by conventional dose rate radiotherapy (CONV-RT) in healthy mice.</div></div><div><h3>Methods</h3><div>Eighty adult male C57BL/6J mice were divided into five groups: Sham, CONV-RT10Gy, CONV-RT20Gy, FLASH-RT10Gy, and FLASH-RT20Gy. Three days post-irradiation, morphological changes in neurons within the dentate gyrus (DG), CA1, and CA3 were observed using hematoxylin and eosin and Nissl staining. The malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), catalase (CAT), and hydroxyl radical (OH<sup>−</sup>) levels were measured using assay kits. Quantitative reverse transcription PCR was used to assess interleukin (IL)-1β, IL-6, inducible nitric oxide synthase (iNOS), and tumor necrosis factor (TNF)-α mRNA expression levels in hippocampus. Immunofluorescence was employed to observe microglial activation in the DG.</div></div><div><h3>Results</h3><div>Compared with Sham, CONV-RT10Gy and CONV-RT20Gy exhibited disorganized neuronal arrangements and blurred nucleoli in the DG; the number of Nissl body was reduced, but FLASH-RT10Gy and FLASH-RT20Gy alleviated these abnormalities. Moreover, FLASH-RT20Gy mitigated the upregulation of MDA and downregulation of GSH, GSH-PX, SOD, CAT, and OH<sup>−</sup> levels in the hippocampus of mice subjected to CONV-RT20Gy. Additionally, FLASH-RT20Gy attenuated the upregulation of IL-1β, IL-6, iNOS, and TNF-α mRNA levels in hippocampus of mice subjected to CONV-RT20Gy and diminished microglial activation in the DG.</div></div><div><h3>Conclusion</h3><div>FLASH-RT mitigate the structural and functional disruptions in hippocampal neurons induced by CONV-RT and alleviate oxidative stress and inflammation in hippocampal tissue by reducing microglial activation.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 2","pages":"Article 100186"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanteng Li , Runzi Wang , Fang Xie , Lingjia Qian , Yong Zhang , Jianning Zhang
{"title":"Compound B vitamins mitigate post-traumatic stress disorder-like behaviors induced by single prolonged stress in rats by inhibiting hippocampal mitochondrial DNA methylation","authors":"Yanteng Li , Runzi Wang , Fang Xie , Lingjia Qian , Yong Zhang , Jianning Zhang","doi":"10.1016/j.jnrt.2025.100187","DOIUrl":"10.1016/j.jnrt.2025.100187","url":null,"abstract":"<div><h3>Background</h3><div>Post-traumatic stress disorder (PTSD) is a serious mental disorder. Current treatments, typically using serotonin reuptake inhibitors, have limited effectiveness and often cause severe adverse effects. In the present study, we investigated whether Compound B vitamins (VBco) have protective effects in improving PTSD-like behaviors and the possible related molecular mechanisms in a rat model of single prolonged stress (SPS).</div></div><div><h3>Methods</h3><div>Eighty adult male rats were randomly divided into four groups (<em>n</em> = 20): control (CTRL), SPS, VBco control (CTRL-VBco), and SPS and VBco (SPS-VBco). After modeling, behavioral tests (including open field test, forced swimming test, sucrose preference test, fear conditioning test) were conducted. Blood was collected to detect plasma homocysteine (Hcy) concentrations. Brain tissue was collected for mitochondrial function analysis, western blotting, and quantitative real-time Polymerase Chain Reaction (PCR).</div></div><div><h3>Results</h3><div>VBco reduced plasma Hcy levels significantly 1 week post-SPS. The SPS-VBco group showed decreased grooming times and increased movement speed in the open field test, less resting time in the forced swim test, increased sucrose preference ratios in the sucrose preference test, and less freezing time in the fear conditioning test. VBco increased the expression of mRNA for subunits of respiratory chain-related protein in hippocampal mitochondria and improved mitochondrial complex I and IV activity and membrane potential in hippocampus. VBco reversed SPS-induced mtND1 and mtND3 methylation in hippocampal mitochondria. VBco downregulated the levels of methyltransferases (DNMT1, DNMT3A, DNMT3B) in hippocampal mitochondria.</div></div><div><h3>Conclusion</h3><div>VBco can inhibit hippocampal mitochondrial DNA methylation effectively. This may be one of the mechanisms by which it attenuates PTSD-like behaviors.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 2","pages":"Article 100187"},"PeriodicalIF":3.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Making smiles and eye closure natural! Application of acupoint injection therapy in facial paralysis comorbidities: A case report","authors":"Yuxin Liu , Xixi Han , Lin Chen , Bin Ma","doi":"10.1016/j.jnrt.2025.100185","DOIUrl":"10.1016/j.jnrt.2025.100185","url":null,"abstract":"<div><div>Facial paralysis comorbidities is now understood to include two distinct forms: synkinesis and micro-entrapment syndrome of nerves innervating the face (MESNIF). These disorders manifest as oromandibular synkinesis, stiffness and atrophy of facial muscles on one side, which affect activities of daily living. Acupoint Injection is a treatment for facial paralysis, combining the meridian theory of traditional Chinese medicine, with the injection of specific drugs into acupuncture points of the face. In recent years, the use of acupoint injections has shown in remarkable clinical efficacy and few adverse effects. We report the case to introduce this integrative therapy and outline the key principles of rehabilitation therapy.</div></div>","PeriodicalId":44709,"journal":{"name":"Journal of Neurorestoratology","volume":"13 2","pages":"Article 100185"},"PeriodicalIF":3.1,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}