Review
Biochemistry & Molecular Biology
Connor A. Wathen, Yohannes G. Ghenbot, Ali K. Ozturk, D. Kacy Cullen, John C. O'Donnell, Dmitriy Petrov
Summary: Large animal models, particularly porcine models, of spinal cord injury are valuable for translational research and evaluation of potential therapies. The anatomical and physiological similarities to humans allow for more representative models and accurate assessment of novel treatments, including biologics. Porcine models also facilitate the collection of physiological data in a clinical-like setting. This review provides an overview of porcine spinal cord injury research, including available models and outcome measures, as well as the strengths, limitations, and alternatives.
Article
Neurosciences
Ming-hao Ge, He Tian, Liang Mao, Dao-yong Li, Jia-quan Lin, Heng-shuo Hu, Shuo-cheng Huang, Chuan-jie Zhang, Xi-fan Mei
Summary: The study demonstrated that zinc can inhibit ferroptosis by regulating the NRF2/HO-1 and GPX4 signaling pathways, exerting a neuroprotective effect in spinal cord injury.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Neurosciences
Merrick C. Strotton, Andrew J. Bodey, Kazimir Wanelik, Carl Hobbs, Christoph Rau, Elizabeth J. Bradbury
Summary: Extensive structural changes occur within the spinal cord following traumatic injury, including acute tissue debris breakdown, chronic cavity formation, and scar development. 3D imaging offers advantages over 2D histology in accurately representing tissue pathology and quantifying the extent of damage.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Yu Zhou, Yong Zhang, Benson O. A. Botchway, Xichen Wang, Xuehong Liu
Summary: Spinal cord injury (SCI) is a serious disease that often causes persistent neurological deficits. Epigenetic changes, specifically DNA methylation, play a crucial role in nerve regeneration, remodeling, and pathophysiological characteristics of SCI. Curcumin, a natural polyphenol, has anti-inflammatory, antioxidant, and neuroprotective effects that can mitigate cell and tissue damage caused by SCI. Pharmacological interventions targeting DNA methylation may hold promise for treating SCI.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Review
Cell Biology
Scott R. Whittemore, Sujata Saraswat Ohri, Michael D. Forston, George Z. Wei, Michal Hetman
Summary: Proteostasis, regulated by multiple pathways, is crucial for cellular and organismal survival. Disruption of proteostasis may lead to cell apoptosis, while maintaining it contributes to the treatment of traumatic spinal cord injury.
Review
Clinical Neurology
Nicolo Marchesini, Laura Lucia Fernandez Londono, Dylan Griswold, Andres Mariano Rubiano
Summary: Management of traumatic spinal cord injury in the early stages in Latin America lacks comprehensive information, and there is high variability among studies in all examined areas. Despite many patients being polytraumatized, little is known about ICU requirements. Treatment is heterogeneous, and many complications are preventable, potentially increasing length of hospital stay, costs, and mortality.
WORLD NEUROSURGERY
(2022)
Review
Neurosciences
Roxana N. Beladi, Kyle S. Varkoly, Lauren Schutz, Liqiang Zhang, Jordan R. Yaron, Qiuyun Guo, Michelle Burgin, Ian Hogue, Wesley Tierney, Wojciech Dobrowski, Alexandra R. Lucas
Summary: Progressive neurological damage following brain or spinal cord trauma leads to motor function loss, with limited treatment options. Early clotting and hemorrhage post SCI and TBI trigger immune cell activation and neuronal damage. Thrombotic and thrombolytic proteases play a role in both healing and damaging immune cell interactions, impacting neuron and glial cell growth.
CURRENT NEUROPHARMACOLOGY
(2021)
Article
Engineering, Biomedical
Xingzhi Liu, Lulu Zhang, Zhongjuan Xu, Xuan Xiong, Yanzhen Yu, Hanfei Wu, Hong Qiao, Junjie Zhong, Zhe Zhao, Jianwu Dai, Guangli Suo
Summary: This study aims to develop genetically engineered miR21-loaded exosomes that can be stably tethered to a collagen-I scaffold, promoting the sustained release of miR21 and benefiting spinal cord injury repair.
ACTA BIOMATERIALIA
(2022)
Review
Immunology
Jiansong Chen, Yiguo Shen, Xiaobo Shao, Weiliang Wu
Summary: Spinal cord injury (SCI) and spinal cord tumor cause significant damage to the spinal cord, leading to multiple impairments and high morbidity and mortality. The treatment options for these conditions are limited and the underlying molecular mechanisms remain unclear. In the review, the role of inflammasomes in SCI and spinal cord tumors is highlighted, and targeting inflammasomes is suggested as a potential therapeutic strategy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Neurosciences
Xiaoping Ren, Weihua Zhang, Jie Qin, Jian Mo, Yi Chen, Jie Han, Xinjian Feng, Sitan Feng, Haibo Liang, Liangjue Cen, Xiaofei Wu, Linxuan Han, Rongyu Lan, Haixuan Deng, Huihui Yao, Zhongquan Qi, Hongjun Gao, Lishan Wei, Shuai Ren
Summary: This study tested spinal cord fusion (SCF) using the neuroprotective agent polyethylene glycol (PEG) in different animal models and developed a new clinical procedure called vascular pedicle hemisected spinal cord transplantation (vSCT) for the treatment of paraplegic patients. The results demonstrated the feasibility and efficacy of vSCT in re-establishing the continuity of spinal nerve fibers, potentially restoring motor, sensory, and autonomic nervous functions in paraplegic patients. Further clinical trials are needed to validate these findings.
CNS NEUROSCIENCE & THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Zili He, Jiqing Du, Yu Zhang, Yitie Xu, Qian Huang, Qingwei Zhou, Min Wu, Yao Li, Xie Zhang, Hongyu Zhang, Yuepiao Cai, Keyong Ye, Xiangyang Wang, Yingze Zhang, Qi Han, Jian Xiao
Summary: Increasing evidence suggests that defects in autophagy and autophagy-lysosomal pathway (ALP) may contribute to endothelial barrier disruption following acute traumatic spinal cord injury (SCI). This study investigates whether Kruppel-like factor 2 (KLF2) coordinates ALP in endothelial cells in SCI. The results demonstrate that KLF2 is a key contributor to SCI-mediated ALP dysfunction and blood-spinal cord barrier (BSCB) disruption, and could be a promising pharmacological target for SCI management and treatment.
Review
Neurosciences
Yi Ding, Qin Chen
Summary: Spinal cord injury (SCI) is a traumatic central nervous system injury that can lead to severe nerve damage. Inflammatory response plays a crucial role in secondary injury. Prolonged inflammation can worsen the injured site's microenvironment, resulting in neural function deterioration. Understanding the NF-kappa B pathway and its regulation of inflammation after SCI is crucial for developing new therapies. Inhibiting the NF-kappa B pathway improves the inflammatory microenvironment and enhances neural function recovery, making it a potential therapeutic target for SCI.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Critical Care Medicine
Michael G. Fehlings, Ali Moghaddamjou, James S. Harrop, Ralph Stanford, Jonathon Ball, Bizhan Aarabi, Brian J. C. Freeman, Paul M. Arnold, James D. Guest, Shekar N. Kurpad, James M. Schuster, Ahmad Nassr, Karl M. Schmitt, Jefferson R. Wilson, Darrel S. Brodke, Faiz U. Ahmad, Albert Yee, Wilson Z. Ray, Nathaniel P. Brooks, Jason Wilson, Diana S-L Chow, Elizabeth G. Toups, Branko Kopjar
Summary: This study evaluated the efficacy and safety of Riluzole in acute cervical spinal cord injury (tSCI). The results showed favorable outcomes in functional recovery for patients with acute cervical tSCI treated with Riluzole. Although the primary analysis did not achieve the predetermined endpoint, pre-planned secondary analyses demonstrated significant gains in functional recovery for all subgroups of cervical SCI subjects.
JOURNAL OF NEUROTRAUMA
(2023)
Article
Biochemistry & Molecular Biology
Tao Jiang, Tao Qin, Peng Gao, Zhiwen Tao, Xiaowei Wang, Mengyuan Wu, Jun Gu, Bo Chu, Ziyang Zheng, Jiang Yi, Tao Xu, Yifan Huang, Hao Liu, Shujie Zhao, Yongxin Ren, Jian Chen, Guoyong Yin
Summary: The expression of SIRT1 in spinal cord endothelial cells is decreased after spinal cord injury (SCI). SIRT1 has the ability to reduce endothelial reactive oxygen species production and protect endothelial barrier function, indicating its potential as a therapeutic target for promoting functional recovery against blood-spinal cord barrier (BSCB) disruption following SCI.
Article
Neurosciences
Shuai Ren, Weihua Zhang, HongMiao Liu, Xin Wang, Xiangchen Guan, Mingzhe Zhang, Jian Zhang, Qiong Wu, Yan Xue, Dan Wang, Yong Liu, Jianyu Liu, Xiaoping Ren
Summary: The study focused on investigating the restoration of motor function following spinal cord injury through transplanting a vascularized pedicle of hemisected spinal cord to bridge the transected spinal cord. Results showed that electrical continuity was restored, leading to motor function recovery, supporting the potential effectiveness of similar operative techniques in treating SCI patients previously considered to have irreversible damage or paralysis.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Review
Cell Biology
Danyon Harkins, Helen M. Cooper, Michael Piper
Summary: The V-SVZ region in adult mammalian central nervous system houses neural stem cells that continue to produce neurons, and its development and function are reliant on different aspects of lipid biology. The region contains two types of cells, aNSCs and ependymal cells, serving important functions in neuronal generation and maintaining a barrier between CSF and parenchyma.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Marija Kojic, Tomasz Gawda, Monika Gaik, Alexander Begg, Anna Salerno-Kochan, Nyoman D. Kurniawan, Alun Jones, Katarzyna Drozdzyk, Anna Koscielniak, Andrzej Chramiec-Glabik, Soroor Hediyeh-Zadeh, Maria Kasherman, Woo Jun Shim, Enakshi Sinniah, Laura A. Genovesi, Rannva K. Abrahamsen, Christina D. Fenger, Camilla G. Madsen, Julie S. Cohen, Ali Fatemi, Zornitza Stark, Sebastian Lunke, Joy Lee, Jonas K. Hansen, Martin F. Boxill, Boris Keren, Isabelle Marey, Margarita S. Saenz, Kathleen Brown, Suzanne A. Alexander, Sergey Mureev, Alina Batzilla, Melissa J. Davis, Michael Piper, Mikael Boden, Thomas H. J. Burne, Nathan J. Palpant, Rikke S. Moller, Sebastian Glatt, Brandon J. Wainwright
Summary: The study identifies biallelic variants in the ELP2 gene causing intellectual disability (ID) and autism spectrum disorder (ASD), which lead to brain abnormalities in patients. The mutations negatively impact the activity of the Elongator complex and its function in brain development.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Cell Biology
Giuseppe Lupo, Michael Piper, Flavio R. Zolessi
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Dermatology
Mitchell E. Fane, Yash Chhabra, Loredana Spoerri, Jacinta L. Simmons, Raquelle Ludwig, Elise Bonvin, Colin R. Goding, Richard A. Sturm, Glen M. Boyle, Nikolas K. Haass, Michael Piper, Aaron G. Smith
Summary: A reciprocal relationship between BRN2 and NOTCH1/2 signaling exists in melanoma cells, bolstering acquisition of invasiveness. Working through the epigenetic modulator EZH2, the BRN2-NOTCH1/2 axis is potentially a key mechanism by which the invasive phenotype is maintained.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Maina Bitar, Christin Weissleder, Hayley F. North, Misaki S. Clearwater, Oressia Zalucki, Glenda M. Halliday, Maree J. Webster, Michael Piper, Cynthia Shannon Weickert, Guy Barry
Summary: This study conducted transcriptomic profiling on human post-mortem tissue from different age stages and found that neuroinflammation becomes more prevalent in the subependymal zone (SEZ) with advancing age, with two distinct time courses.
SCIENTIFIC REPORTS
(2022)
Review
Neurosciences
Lachlan A. Jolly, Raman Kumar, Peter Penzes, Michael Piper, Jozef Gecz
Summary: This review discusses the roles and importance of deubiquitinating enzymes (DUBs) in neurodevelopmental disorders (NDDs). Current genetic evidence and functional studies show that DUBs are associated with various NDDs and their study provides insights into protein degradation during brain development. The regulation of protein networks by DUBs and their connection to NDD genes offer opportunities for developing new therapeutic approaches.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Reproductive Biology
Raul Ayala Davila, Cassy Spiller, Danyon Harkins, Tracey Harvey, Philip W. Jordan, Richard M. Gronostajski, Michael Piper, Josephine Bowles
Summary: Members of the NFI family play essential roles in stem cell biology during development, and their expression patterns in the seminiferous tubules show distinct patterns. NFIX is found to be critical for meiotic progression during spermatogenesis. Its deletion leads to defective synaptonemal complex and unrepaired DNA double-strand breaks in spermatocytes.
BIOLOGY OF REPRODUCTION
(2022)
Article
Developmental Biology
Behzad Yaghmaeian Salmani, Brad Balderson, Susanne Bauer, Helen Ekman, Annika Starkenberg, Thomas Perlmann, Michael Piper, Mikael Boden, Stefan Thor
Summary: This study reveals the impact of the loss of H3K27me3 on the development of specific neuronal subtypes in the hypothalamus, highlighting the unique sensitivity of certain subtypes to disruptions in the epigenomic landscape.
Article
Medicine, Research & Experimental
Monika Gaik, Marija Kojic, Megan R. Stegeman, Tulay Oncu-Oner, Anna Koscielniak, Alun Jones, Ahmed Mohamed, Pak Yan Stefanie Chau, Sazia Sharmin, Andrzej Chramiec-Glabik, Paulina Indyka, Anna Biela, Dominika Dobosz, Amanda Millar, Vann Chau, Aycan Unalp, Michael Piper, Mark C. Bellingham, Evan E. Eichler, Deborah A. Nickerson, Handan Guleryuz, Nour El Hana Abbassi, Konrad Jazgar, Melissa J. Davis, Saadet Mercimek-Andrews, Sultan Cingoz, Brandon J. Wainwright, Sebastian Glatt
Summary: The study identifies ELP4 and ELP6 variants in patients with developmental delay, epilepsy, intellectual disability, and motor dysfunction. Mutations in Elp456 affect Elongator's tRNA modification activity and lead to neurological defects. Elp123 and Elp456 subcomplexes show differences in individual tRNA species and neurodevelopment.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Danyon Harkins, Tracey J. Harvey, Cooper Atterton, Ingrid Miller, Laura Currey, Sabrina Oishi, Maria Kasherman, Raul Ayala Davila, Lucy Harris, Kathryn Green, Hannah Piper, Robert G. Parton, Stefan Thor, Helen M. Cooper, Michael Piper
Summary: The transcription factor NFIX plays a pivotal role in the regulation of cell adhesion within ependymal cells of the lateral ventricles, with Nfix(-/-) mice exhibiting abnormal cilia structure and disrupted localization of adhesion proteins.
Article
Endocrinology & Metabolism
Kreepa G. Kooblall, Mark Stevenson, Michelle Stewart, Lachlan Harris, Oressia Zalucki, Hannah Dewhurst, Natalie Butterfield, Houfu Leng, Tertius A. Hough, Da Ma, Bernard Siow, Paul Potter, Roger D. Cox, Stephen D. M. Brown, Nicole Horwood, Benjamin Wright, Helen Lockstone, David Buck, Tonia L. Vincent, Fadil M. Hannan, J. H. Duncan Bassett, Graham R. Williams, Kate E. Lines, Michael Piper, Sara Wells, Lydia Teboul, Raoul C. Hennekam, Rajesh V. Thakker
Summary: The NFIX gene is associated with two allelic disorders, MAL and MSS, which are characterized by developmental, skeletal, and neural abnormalities. Mutations in exon 2 lead to NFIX haploinsufficiency in MAL, while mutations in exons 6-10 result in the production of dominant-negative mutant NFIX proteins in MSS. In this study, mouse models with exon 7 deletions were generated to investigate the in vivo effects of MSS-associated NFIX mutations. The Nfix(Del2/Del2) mice exhibited developmental abnormalities in skeletal and neural tissues, providing a model for studying the consequences of NFIX mutants that escape nonsense-mediated decay in MSS.
Review
Cell Biology
Benjamin Mitchell, Stefan Thor, Michael Piper
Summary: This article summarizes the diverse roles of SETD2 in mammalian cellular functions and development, with a particular focus on the central nervous system (CNS). The consequences of SETD2 variants in human disease are also discussed, along with future directions for understanding essential cellular functions of SETD2.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biochemical Research Methods
Brad Balderson, Michael Piper, Stefan Thor, Mikael Boden
Summary: Cytocipher is a bioinformatics method and software package that statistically determines significant clusters, overcoming the challenges of manual curation in single-cell RNA-seq analysis. Its application to various datasets revealed previously unidentified cell types and demonstrated high performance on large-scale data.
