ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration
Open accessAbstract
We report here that amyotrophic lateral sclerosis-linked superoxide dismutase 1 (SOD1) mutants with different biochemical characteristics disrupted the blood-spinal cord barrier in mice by reducing the levels of the tight junction proteins ZO-1, occludin and claudin-5 between endothelial cells. This resulted in microhemorrhages with release of neurotoxic hemoglobin-derived products, reductions in microcirculation and hypoperfusion. SOD1 mutant-mediated endothelial damage accumulated before motor neuron degeneration and the neurovascular inflammatory response occurred, indicating that it was a central contributor to disease initiation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Studies in SOD1 transgenic mice expressing dismutase-active (G93A and G37R) and dismutase-inactive (G85R) mutations have suggested that BSCB breakdown occurs before motor neuron injury.
“Studies in SOD1 transgenic mice expressing dismutase-active (G93A and G37R) and dismutase-inactive (G85R) mutations have suggested that BSCB breakdown occurs before motor neuron injury (194, 415, 651, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
The passage describing IgG leakage (provided passage 2) reports substantial BSCB breakdown in G93A, G37R and G85R mice before motor neuron loss. It says leakage was **prior to or contemporaneous with** initial axonal withdrawal, however, so the broader claim that breakdown occurred before motor neuron injury is not established for every line. The supplied copy labels this passage Abstract and gives no page number. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBBB disruption including diminished levels of tight junction proteins, IgG and hemosiderin perivascular deposits, and GLUT1 reduction has been shown to precede neuroinflammation, motor neuron loss, and motor impairment in different types of SOD1 mutants.
“BBB disruption including diminished levels of TJ proteins, immunoglobulin G (IgG) and hemosiderin perivascular deposits, and GLUT1 reduction has been shown to precede neuroinflammation, motor neuron loss, and motor impairment in different types of SOD1 mutants (415, 687, 688).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
The supplied passages (labeled Abstract; Figs. 1–2) report early tight-junction protein reductions, IgG leakage, and hemosiderin deposits in multiple SOD1-mutant mouse lines, before motor neuron loss and inflammatory changes. But the Fig. 2a passage explicitly says that Glut1 levels were not affected by the SOD1 mutation, contrary to the claimed GLUT1 reduction. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSOD1 G93A mice develop ultrastructural capillary alterations, extravasation of red blood cells, and deposition of fibrin(ogen) and hemosiderin deposits in the brain stem and spinal cord early in the disease.
“For instance, SOD1 G93A mice develop ultrastructural capillary alterations, extravasation of RBCs, and deposition of fibrin(ogen) and hemosiderin deposits in the brain stem and spinal cord early in the disease (194, 651, 687).”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [687]
The paper reports capillary ultrastructural changes and presymptomatic hemosiderin deposits in SOD1 G93A mice, mainly in the spinal cord’s anterior horn (Abstract, no page given). It discusses extravasated red blood cells in connection with microhemorrhages, but the passages do not report fibrin(ogen) deposits or establish the claimed findings in the brain stem. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Self-citationALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Velde, C. V., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,426 · see citing works
Self-citationOosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Dorpe, J. V., Hellings, P., Gorselink, M., Heymans, S., et al. (2001) · Nature Genetics · doi:10.1038/88842 · Cited by 1,007 · see citing works
Neurovascular mechanisms of Alzheimer's neurodegeneration
Zloković, B. V. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.02.001 · Cited by 921 · see citing works
Lambrechts, D., Storkebaum, E., Morimoto, M., Del‐Favero, J., Smet, F. D., Marklund, S. L., Wyns, S., Thijs, V., Andersson, J., van Marion, I., et al. (2003) · Nature Genetics · doi:10.1038/ng1211 · Cited by 853 · see citing works
Pun, S., Santos, A. F., Saxena, S., Xu, L., & Caroni, P. (2006) · Nature Neuroscience · doi:10.1038/nn1653 · Cited by 659 · see citing works
Axonal damage markers in cerebrospinal fluid are increased in ALS
Brettschneider, J., Petzold, A., Süßmuth, S. D., Ludolph, A. C., & Tumani, H. (2006) · Neurology · doi:10.1212/01.wnl.0000203120.85850.54 · Cited by 261 · see citing works
Garbuzova-Davis, S. N., Saporta, S., Haller, E. M., Kolomey, I., Bennett, S. P., Potter, H., & Sanberg, P. R. (2007) · PLoS ONE · doi:10.1371/journal.pone.0001205 · Cited by 248 · see citing works
Ultrastructure of blood–brain barrier and blood–spinal cord barrier in SOD1 mice modeling ALS
Garbuzova-Davis, S., Haller, E., Saporta, S., Kolomey, I., Nicosia, S. V., & Sanberg, P. R. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.044 · Cited by 239 · see citing works
Pasinelli, P., Borchelt, D., Houseweart, M. K., Cleveland, D. W., & Brown, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15763 · Cited by 221 · see citing works
Self-citationMicroglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis
Sargsyan, S. A., Monk, P. N., & Shaw, P. J. (2005) · Glia · doi:10.1002/glia.20210 · Cited by 203 · see citing works
Lobsiger, C. S., Boillée, S., & Cleveland, D. W. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702230104 · Cited by 139 · see citing works
Self-citationKamei, Y., Inagaki, N., Nishizawa, M., Tsutsumi, O., Taketani, Y., & Inagaki, M. (1998) · Glia · doi:10.1002/(sici)1098-1136(199807)23:3 · Cited by 114 · see citing works
Toxic Effect of Hemoglobin on Spinal Cord Neurons in Culture
Regan, R. F., & Guo, Y. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.645 · Cited by 73 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897 · see citing works
Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.188 · Cited by 3,076 · see citing works
Self-citationNeurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders
Zlokovic, B. V. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3114 · Cited by 2,969 · see citing works
The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease
Iadecola, C. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.030 · Cited by 2,480 · see citing works
Development, maintenance and disruption of the blood-brain barrier
Obermeier, B., Daneman, R., & Ransohoff, R. M. (2013) · Nature Medicine · doi:10.1038/nm.3407 · Cited by 2,452 · see citing works
Blood-Brain Barrier: From Physiology to Disease and Back
Sweeney, M. D., Zhao, Z., Montagne, A., Nelson, A. R., & Zlokovic, B. V. (2019) · Physiological Reviews · doi:10.1152/physrev.00050.2017 · Cited by 2,294 · see citing works
Bell, R. D., Winkler, E. A., Sagare, A. P., Singh, I., LaRue, B., Deane, R., & Zlokovic, B. V. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.043 · Cited by 1,448 · see citing works
Self-citationReactive Gliosis and the Multicellular Response to CNS Damage and Disease
Burda, J. E., & Sofroniew, M. V. (2014) · Neuron · doi:10.1016/j.neuron.2013.12.034 · Cited by 1,431 · see citing works
Pericytes of the neurovascular unit: key functions and signaling pathways
Sweeney, M. D., Ayyadurai, S., & Zlokovic, B. V. (2016) · Nature Neuroscience · doi:10.1038/nn.4288 · Cited by 1,125 · see citing works
Mfsd2a is critical for the formation and function of the blood-brain barrier
Ben-Zvi, A., Lacoste, B., Kur, E., Andreone, B. J., Mayshar, Y., Yan, H., & Gu, C. (2014) · Nature · doi:10.1038/nature13324 · Cited by 1,037 · see citing works
Central nervous system pericytes in health and disease
Winkler, E. A., Bell, R. D., & Zlokovic, B. V. (2011) · Nature Neuroscience · doi:10.1038/nn.2946 · Cited by 962 · see citing works
Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008 · see citing works
Self-citationThe changing scene of amyotrophic lateral sclerosis
Robberecht, W., & Philips, T. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3430 · Cited by 957 · see citing works
Neurovascular mechanisms and blood–brain barrier disorder in Alzheimer’s disease
Bell, R. D., & Zlokovic, B. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0522-3 · Cited by 892 · see citing works
Kang, S., Fukaya, M., Yang, J. K., Rothstein, J., & Bergles, D. (2010) · Neuron · doi:10.1016/j.neuron.2010.09.009 · Cited by 778 · see citing works
The blood–brain barrier in health and disease
Daneman, R. (2012) · Annals of Neurology · doi:10.1002/ana.23648 · Cited by 756 · see citing works
Brain metabolism in health, aging, and neurodegeneration
Camandola, S., & Mattson, M. P. (2017) · The EMBO Journal · doi:10.15252/embj.201695810 · Cited by 752 · see citing works
The blood-brain barrier in aging and neurodegeneration
Knox, E. G., Aburto, M. R., Clarke, G., Cryan, J. F., & O’Driscoll, C. M. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01511-z · Cited by 738 · see citing works
Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease
Argaw, A. T., Asp, L., Zhang, J., Navrazhina, K., Pham, T., Mariani, J. N., Mahase, S., Dutta, D. J., Seto, J., Kramer, E. G., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60842 · Cited by 733 · see citing works
Alzheimer’s disease: A matter of blood–brain barrier dysfunction?
Montagne, A., Zhao, Z., & Zlokovic, B. V. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20171406 · Cited by 672 · see citing works
The blood-brain barrier: an engineering perspective
Wong, A. D., Ye, M., Levy, A. F., Rothstein, J. D., Bergles, D. E., & Searson, P. C. (2013) · Frontiers in Neuroengineering · doi:10.3389/fneng.2013.00007 · Cited by 662 · see citing works
VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown
Argaw, A. T., Gurfein, B. T., Zhang, Y., Zameer, A., & John, G. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808698106 · Cited by 666 · see citing works
Brain Tissue Responses to Neural Implants Impact Signal Sensitivity and Intervention Strategies
Kozai, T. D. Y., Jaquins-Gerstl, A. S., Vazquez, A. L., Michael, A. C., & Cui, X. T. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn500256e · Cited by 622 · see citing works
Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target
Barber, S. C., & Shaw, P. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.11.018 · Cited by 617 · see citing works
A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice
Saxena, S., Cabuy, E., & Caroni, P. (2009) · Nature Neuroscience · doi:10.1038/nn.2297 · Cited by 600 · see citing works
The dynamic blood–brain barrier
Keaney, J., & Campbell, M. (2015) · The FEBS Journal · doi:10.1111/febs.13412 · Cited by 616 · see citing works
Saxena, S., & Caroni, P. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.031 · Cited by 561 · see citing works
The blood–spinal cord barrier: Morphology and Clinical Implications
Bartanusz, V., Ježová, D., Alajajian, B., & Digicaylioglu, M. H. (2011) · Annals of Neurology · doi:10.1002/ana.22421 · Cited by 479 · see citing works
Adibhatla, R. M., & Hatcher, J. F. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2668 · Cited by 480 · see citing works
Motor Neuron Diversity in Development and Disease
Kanning, K. C., Kaplan, A., & Henderson, C. E. (2010) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135722 · Cited by 472 · see citing works
The Role of Environmental Exposures in Neurodegeneration and Neurodegenerative Diseases
Cannon, J. R., & Greenamyre, J. T. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr239 · Cited by 462 · see citing works
Neurological Diseases in Relation to the Blood–Brain Barrier
Rosenberg, G. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.197 · Cited by 442 · see citing works
Blood–spinal cord barrier breakdown and pericyte reductions in amyotrophic lateral sclerosis
Winkler, E. A., Sengillo, J. D., Sullivan, J. S., Henkel, J. S., Appel, S. H., & Zlokovic, B. V. (2013) · Acta Neuropathologica · doi:10.1007/s00401-012-1039-8 · Cited by 354 · see citing works
Yamanaka, K., Boillee, S., Roberts, E. A., Garcia, M. L., McAlonis-Downes, M., Mikse, O. R., Cleveland, D. W., & Goldstein, L. S. B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802556105 · Cited by 309 · see citing works
Self-citationCai, W., Zhang, K., Li, P., Zhu, L., Xu, J., Yang, B., Hu, X., Lu, Z., & Chen, J. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.006 · Cited by 288 · see citing works
The Pericyte: A Forgotten Cell Type with Important Implications for A lzheimer's Disease?
Winkler, E. A., Sagare, A. P., & Zloković, B. V. (2014) · Brain Pathology · doi:10.1111/bpa.12152 · Cited by 275 · see citing works
Self-citationBarrier function in the peripheral and central nervous system—a review
Reinhold, A., & Rittner, H. L. (2016) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-016-1920-8 · Cited by 279 · see citing works
Glial cells in amyotrophic lateral sclerosis
Philips, T., & Rothstein, J. D. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.05.015 · Cited by 255 · see citing works
Neurovascular Dysfunction and Faulty Amyloid -Peptide Clearance in Alzheimer Disease
Sagare, A. P., Bell, R. D., & Zlokovic, B. V. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011452 · Cited by 251 · see citing works
Self-citationNeurovascular Unit Dysfunction and Neurodegenerative Disorders
Yu, X., Ji, C., & Shao, A. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00334 · Cited by 244 · see citing works
Tsuda, H., Han, S. M., Yang, Y., Tong, C., Qi, L. Y., Mohan, K., Haueter, C. M., Zoghbi, A. W., Harati, Y., Kwan, J. Y., et al. (2008) · Cell · doi:10.1016/j.cell.2008.04.039 · Cited by 243 · see citing works
Brain Endothelial Cells Are Exquisite Sensors of Age-Related Circulatory Cues
Chen, M. B., Yang, A. C., Yousef, H., Lee, D., Chen, W., Schaum, N., Lehallier, B., Quake, S. R., & Wyss-Coray, T. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.012 · Cited by 233 · see citing works
Impaired blood–brain/spinal cord barrier in ALS patients
Garbuzova-Davis, S. N., Hernandez‐Ontiveros, D. G., Rodrigues, M. C. O., Haller, E. M., Frisina-Deyo, A. J., Mirtyl, S., Sallot, S. A., Saporta, S., Borlongan, C. V., & Sanberg, P. R. (2012) · Brain Research · doi:10.1016/j.brainres.2012.05.056 · Cited by 240 · see citing works
Blood–Spinal Cord Barrier Pericyte Reductions Contribute to Increased Capillary Permeability
Winkler, E. A., Sengillo, J. D., Bell, R. D., Wang, J., & Zlokovic, B. V. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.113 · Cited by 226 · see citing works
Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview
Archie, S. R., Shoyaib, A. A., & Cucullo, L. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111779 · Cited by 232 · see citing works
Winkler, E. A., Sengillo, J. D., Sagare, A. P., Zhao, Z., Ma, Q., Zuniga, E., Wang, Y., Zhong, Z., Sullivan, J. S., Griffin, J. H., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1401595111 · Cited by 238 · see citing works
Self-citationAnesthesia and Surgery Impair Blood–Brain Barrier and Cognitive Function in Mice
Yang, S., Gu, C.-P., Mandeville, E. T., Dong, Y., Esposito, E., Zhang, Y., Yang, G., Shen, Y., Fu, X., Lo, E. H., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00902 · Cited by 226 · see citing works
Cellular Senescence, Vascular Disease, and Aging
Kovacic, J. C., Moreno, P., Nabel, E. G., Hachinski, V., & Fuster, V. (2011) · Circulation · doi:10.1161/circulationaha.110.009118 · Cited by 222 · see citing works
Emerging roles of PGE2 receptors in models of neurological disease
Andreasson, K. I. (2009) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2009.04.003 · Cited by 218 · see citing works
Endo, F., Komine, O., Fujimori-Tonou, N., Katsuno, M., Jin, S., Watanabe, S., Sobue, G., Dezawa, M., Wyss-Coray, T., & Yamanaka, K. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.053 · Cited by 207 · see citing works
Cellular Senescence, Vascular Disease, and Aging
Kovacic, J. C., Moreno, P., Hachinski, V., Nabel, E. G., & Fuster, V. (2011) · Circulation · doi:10.1161/circulationaha.110.007021 · Cited by 204 · see citing works
Foust, K. D., Salazar, D. L., Likhite, S. B., Ferraiuolo, L., Ditsworth, D., Ilieva, H. S., Meyer, K., Schmelzer, L., Braun, L., Cleveland, D. W., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.211 · Cited by 205 · see citing works
Self-citationThe impact of cerebrovascular aging on vascular cognitive impairment and dementia
Yang, T., Sun, Y., Lu, Z., Leak, R. K., & Zhang, F. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.007 · Cited by 206 · see citing works
Microglia centered pathogenesis in ALS: insights in cell interconnectivity
Brites, D. M. T. O., & Vaz, A. R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00117 · Cited by 201 · see citing works
Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases
Grammas, P., Martinez, J. M., & Miller, B. B. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399411001918 · Cited by 203 · see citing works
Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis
Miyazaki, K., Ohta, Y., Nagai, M., Morimoto, N., Kurata, T., Takehisa, Y., Ikeda, Y., Matsuura, T., & Abe, K. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22594 · Cited by 197 · see citing works
Neurodegeneration and the neurovascular unit
Zloković, B. V. (2010) · Nature Medicine · doi:10.1038/nm1210-1370 · Cited by 190 · see citing works
Martínez, H. R., Molina-López, J. F., González‐Garza, M. T., Moreno-Cuevas, J. E., Caro-Osorio, E., Gil-Valadez, A. H., Gutiérrez‐Jiménez, E., Zazueta, O. E., Meza, J. A., Couret-Alcaraz, P., et al. (2011) · Cell Transplantation · doi:10.3727/096368911x582769 · Cited by 183 · see citing works
Control of Motoneuron Survival by Angiogenin
Kieran, D., Sebastià, J., Greenway, M. J., King, M. A., Connaughton, D. M., Concannon, C. G., Fenner, B. J., Hardiman, O. M., & Prehn, J. H. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3399-08.2008 · Cited by 183 · see citing works
Inflammation and neurovascular changes in amyotrophic lateral sclerosis
Evans, M. C., Couch, Y., Sibson, N. R., & Turner, M. R. (2012) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.10.008 · Cited by 176 · see citing works
Zhong, Z., Ilieva, H., Hallagan, L., Bell, R., Singh, I., Paquette, N., Thiyagarajan, M., Deane, R., Fernandez, J. A., Lane, S., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38476 · Cited by 176 · see citing works
Self-citationVinsant, S. L., Mansfield, C., Jiménez-Moreno, R., Moore, V. D. G., Yoshikawa, M., Hampton, T., Prevette, D. M., Caress, J. B., Oppenheim, R. W., & Milligan, C. (2013) · Brain and Behavior · doi:10.1002/brb3.142 · Cited by 175 · see citing works
The Complex Molecular Biology of Amyotrophic Lateral Sclerosis (ALS)
Redler, R. L., & Dokholyan, N. V. (2012) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385883-2.00002-3 · Cited by 172 · see citing works
Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development
Sances, S., Ho, R., Vatine, G. D., West, D., Laperle, A., Meyer, A. S., Godoy, M. I., Kay, P., Mandefro, B., Hatata, S., et al. (2018) · Stem Cell Reports · doi:10.1016/j.stemcr.2018.02.012 · Cited by 169 · see citing works
Schmid, B., Hruscha, A., Hogl, S., Banzhaf‐Strathmann, J., Strecker, K., van der Zee, J., Teucke, M., Eimer, S., Hegermann, J., Kittelmann, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218311110 · Cited by 170 · see citing works
Ramesh, T., Lyon, A. N., Pineda, R., Wang, C., Janssen, P. M. L., Canan, B. D., Burghes, A. H. M., & Beattie, C. E. (2010) · Disease Models & Mechanisms · doi:10.1242/dmm.005538 · Cited by 164 · see citing works
On the assessment of cerebrovascular reactivity using hypercapnia BOLD MRI
Yezhuvath, U. S., Lewis‐Amezcua, K., Varghese, R., Xiao, G., & Lu, H. (2009) · NMR in Biomedicine · doi:10.1002/nbm.1392 · Cited by 157 · see citing works
Impaired blood–brain and blood–spinal cord barriers in mutant SOD1-linked ALS rat
Nicaise, C., Mitrecic, D., Demetter, P., De Decker, R., Authelet, M., Boom, A., & Pochet, R. (2009) · Brain Research · doi:10.1016/j.brainres.2009.09.018 · Cited by 168 · see citing works
Oksanen, M., Lehtonen, Š., Jaronen, M., Goldsteins, G., Hämäläinen, R. H., & Koıstınaho, J. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03111-7 · Cited by 156 · see citing works
In vitro modeling of the neurovascular unit: advances in the field
Bhalerao, A., Sivandzade, F., Archie, S. R., Chowdhury, E. A., Noorani, B., & Cucullo, L. (2020) · Fluids and Barriers of the CNS · doi:10.1186/s12987-020-00183-7 · Cited by 148 · see citing works
Kozai, T. D. Y., Li, X., Bodily, L. M., Caparosa, E. M., Zenonos, G. A., Carlisle, D. L., Friedlander, R. M., & Cui, X. T. (2014) · Biomaterials · doi:10.1016/j.biomaterials.2014.08.006 · Cited by 136 · see citing works
Blood-CNS Barrier Impairment in ALS patients versus an animal model
Garbuzova-Davis, S. N., & Sanberg, P. R. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00021 · Cited by 146 · see citing works
Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis
Sutedja, N. A., van der Schouw, Y. T., Fischer, K., Sizoo, E. M., Huisman, M. H. B., Veldink, J. H., & van den Berg, L. H. (2011) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2010.236752 · Cited by 144 · see citing works
Occludin Protein Family: Oxidative Stress and Reducing Conditions
Blasig, I. E., Bellmann, C., Cording, J., Vecchio, G. D., Zwanziger, D., Huber, O., & Haseloff, R. F. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3542 · Cited by 139 · see citing works
DECREASED mRNA EXPRESSION OF TIGHT JUNCTION PROTEINS IN LUMBAR SPINAL CORDS OF PATIENTS WITH ALS
Henkel, J. S., Beers, D. R., Wen, S., Bowser, R., & Appel, S. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a41228 · Cited by 153 · see citing works
Guo, S., & Lo, E. H. (2008) · Stroke · doi:10.1161/strokeaha.108.534388 · Cited by 135 · see citing works
Glycosphingolipids are modulators of disease pathogenesis in amyotrophic lateral sclerosis
Dodge, J. C., Treleaven, C. M., Pacheco, J., Cooper, S., Bao, C., Abraham, M., Cromwell, M. A., Sardi, S. P., Chuang, W., Sidman, R. L., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1508767112 · Cited by 134 · see citing works
Rabin, S. J., Kim, J. M., Baughn, M. W., Libby, R. T., Kim, Y. J., Fan, Y., Libby, R. T., Spada, A. R. L., Stone, B. C., & Ravits, J. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp498 · Cited by 134 · see citing works
Inflammation in ALS and SMA: Sorting out the good from the evil
Papadimitriou, D. A., Verche, V. L., Jacquier, A., Ikiz, B., Przedborski, S., & Ré, D. B. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.10.005 · Cited by 132 · see citing works
Amyotrophic lateral sclerosis: A neurovascular disease
Garbuzova-Davis, S. N., Rodrigues, M. C. O., Hernandez‐Ontiveros, D. G., Louis, M. K., Willing, A. E., Borlongan, C. V., & Sanberg, P. R. (2011) · Brain Research · doi:10.1016/j.brainres.2011.04.049 · Cited by 128 · see citing works
Cytoprotective protein C pathways and implications for stroke and neurological disorders
Zlokovic, B. V., & Griffin, J. H. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.01.005 · Cited by 128 · see citing works
Rodent models of TDP-43: Recent advances
Tsao, W., Jeong, Y. H., Lin, S. Z., Ling, J. P., Price, D. L., Chiang, P., & Wong, P. C. (2012) · Brain Research · doi:10.1016/j.brainres.2012.04.031 · Cited by 126 · see citing works
Metabolic signatures of amyotrophic lateral sclerosis reveal insights into disease pathogenesis
Dodge, J. C., Treleaven, C. M., Fidler, J. A., Tamsett, T. J., Bao, C., Searles, M., Taksir, T. V., Misra, K., Sidman, R. L., Cheng, S. H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308421110 · Cited by 125 · see citing works
Developmental and pathological angiogenesis in the central nervous system
Vallon, M., Chang, J., Zhang, J. H., & Kuo, C. J. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1625-0 · Cited by 124 · see citing works
Revisiting the blood-brain barrier: A hard nut to crack in the transportation of drug molecules
Harilal, S., Jose, J., Parambi, D. G. T., Kumar, R., Unnikrishnan, M. K., Uddin, M. S., Mathew, G. E., Pratap, R., Marathakam, A., & Mathew, B. (2020) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2020.03.018 · Cited by 124 · see citing works
Altered perivascular fibroblast activity precedes ALS disease onset
Månberg, A., Skene, N., Sanders, F., Trusohamn, M., Remnestål, J., Szczepińska, A., Aksoylu, I. S., Lönnerberg, P., Ebarasi, L., Wouters, S., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01295-9 · Cited by 120 · see citing works
Zhu, D., Wang, Y., Singh, I., Bell, R. D., Deane, R., Zhong, Z., Sagare, A. P., Winkler, E. A., & Zloković, B. V. (2010) · Blood · doi:10.1182/blood-2010-01-262386 · Cited by 115 · see citing works
Self-citationAmyotrophic Lateral Sclerosis: A Neurodegenerative Motor Neuron Disease With Ocular Involvement
Rojas, P., Ramirez, A. I., Fernández‐Albarral, J. A., López‐Cuenca, I., Salobrar‐García, E., Cadena, M., Elvira‐Hurtado, L., Salazar, J. J., de Hoz, R., & Ramirez, J. M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.566858 · Cited by 116 · see citing works
Nizzardo, M., Simone, C., Rizzo, F., Ruggieri, M., Salani, S., Riboldi, G. M., Faravelli, I., Zanetta, C., Bresolin, N., Comi, G. P., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt425 · Cited by 112 · see citing works
Glial Cells in Amyotrophic Lateral Sclerosis
Lasiene, J., & Yamanaka, K. (2011) · Neurology Research International · doi:10.1155/2011/718987 · Cited by 110 · see citing works
Role of non-neuronal nicotinic acetylcholine receptors in angiogenesis
Arias, H. R., Richards, V. E., Ng, D., Ghafoori, M. E., Le, V., & Mousa, S. A. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.01.013 · Cited by 108 · see citing works
Degeneration and repair in central nervous system disease
Lo, E. H. (2010) · Nature Medicine · doi:10.1038/nm.2226 · Cited by 109 · see citing works
Aronica, E., Baas, F., Iyer, A. M., ten Asbroek, A. L. M. A., Morello, G., & Cavallaro, S. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.12.002 · Cited by 107 · see citing works
Bataveljić, D., Nikolic, L. M., Milosevic, M. M., Todorović, N. V., & Anđjus, P. R. (2012) · Glia · doi:10.1002/glia.22414 · Cited by 106 · see citing works
Radford, R. A. W., Morsch, M., Rayner, S. L., Cole, N. J., Pountney, D. L., & Chung, R. S. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00414 · Cited by 102 · see citing works
Lee, J. D., Kumar, V., Fung, J. N., Ruitenberg, M. J., Noakes, P. G., & Woodruff, T. M. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13730 · Cited by 100 · see citing works
Biphasic Mechanisms of Neurovascular Unit Injury and Protection in CNS Diseases
Maki, T., Hayakawa, K., Pham, L. D., Xing, C., Lo, E. H., & Arai, K. (2013) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527311312030004 · Cited by 101 · see citing works
Sonobe, Y., Takeuchi, H., Kataoka, K., Li, H., Jin, S., Mimuro, M., Hashizume, Y., Sano, Y., Kanda, T., Mizuno, T., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.025940 · Cited by 99 · see citing works
Lee, J., Choi, H., Ahn, H., Ju, B., & Yune, T. (2014) · American Journal of Pathology · doi:10.1016/j.ajpath.2014.07.016 · Cited by 93 · see citing works
Vascular D efects and S pinal C ord H ypoxia in S pinal M uscular A trophy
Somers, E., Lees, R. D., Hoban, K., Sleigh, J. N., Zhou, H., Francesco Muntoni, A., Talbot, K., Gillingwater, T. H., & Parson, S. H. (2015) · Annals of Neurology · doi:10.1002/ana.24549 · Cited by 96 · see citing works
- Authors
- Zhong, Z., Deane, R., Ali, Z., Parisi, M., Shapovalov, Y., O'Banion, M. K., Stojanovic, K., Sagare, A., Boillee, S., Cleveland, D. W., & Zlokovic, B. V.
- Affiliations
- University of Rochester Medicine (US)
- Ludwig Cancer Research (BE)
- Venue
- Nature Neuroscience
- Published
- 2008-03-16
- Volume
- 11
- Issue
- 4
- Pages
- 420-422
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2895310
- OpenAlex
- W1968758728
- Cited by
- 476
- References
- 15
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 29 · 2023: 26 · 2022: 20 · 2021: 33 · 2020: 27 · 2019: 26 · 2018: 22 · 2017: 18 · 2016: 18 · 2015: 25 · 2014: 32 · 2013: 28 · 2012: 31
- FWCI
- 23.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R37AG023084)
- National Heart, Lung, and Blood Institute (HL63290, R01HL063290)
- National Institute of Neurological Disorders and Stroke (R37NS034467, R37 NS 27036, R37NS027036, R01NS034467, R37NS34467)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Keywords
- amyotrophic lateral sclerosis, mutant SOD1, blood-spinal cord barrier, tight junction proteins, ZO-1, occludin, claudin-5, endothelial injury, microhemorrhages, microcirculation, hypoperfusion, neurovascular inflammation, motor neuron degeneration, disease initiation
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Blood-Brain Barrier, Capillaries, Endothelium, Vascular, Hemorrhage, Humans, Isoenzymes, Membrane Proteins, Mice, Mutant Strains, Motor Neurons, Nerve Degeneration, Phosphoproteins, Spinal Cord, Superoxide Dismutase, Disease Progression, Tight Junctions, Mice, Claudin-5, Occludin, Zonula Occludens-1 Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
