The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Recommendations for Standards Regarding Preclinical Neuroprotective and Restorative Drug Development
Open accessAbstract
Abstract —The plethora of failed clinical trials with neuroprotective drugs for acute ischemic stroke have raised justifiable concerns about how best to proceed for the future development of such interventions. Preclinical testing of neuroprotective drugs is an important aspect of assessing their therapeutic potential, but guidelines concerning how to perform preclinical development of purported neuroprotective drugs for acute ischemic stroke are lacking. This conference of academicians and industry representatives was convened to suggest such guidelines for the preclinical evaluation of neuroprotective drugs and to recommend to potential clinical investigators the data they should review to reassure themselves that a particular neuroprotective drug has a reasonable chance to succeed in an appropriately designed clinical trial. Without rigorous, robust, and detailed preclinical evaluation, it is unlikely that novel neuroprotective drugs will prove to be effective when tested in large, time-consuming, and expensive clinical trials. Additionally, similar recommendations are provided for drugs with the potential to enhance recovery after acute ischemic stroke, a burgeoning new field with great potential but little currently available data. The suggestions contained in this document are meant to serve as overall guidelines that must be adapted to the individual characteristics related to particular drugs and their preclinical and clinical development needs.
Overview
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
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Tissue Plasminogen Activator for Acute Ischemic Stroke
(1995) · New England Journal of Medicine · doi:10.1056/nejm199512143332401 · Cited by 11,654
Nudo, R. J., Wise, B. M., SiFuentes, F., & Milliken, G. W. (1996) · Science · doi:10.1126/science.272.5269.1791 · Cited by 1,911
Cited by
Zeng, X., Zhang, Y., Kwong, J. S. W., Zhang, C., Li, S., Sun, F., Niu, Y., & Du, L. (2015) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12141 · Cited by 2,082
Ma, L.-L., Wang, Y.-Y., Yang, Z.-H., Huang, D., Weng, H., & Zeng, X.-T. (2020) · Military Medical Research · doi:10.1186/s40779-020-00238-8 · Cited by 1,648
Can Animal Models of Disease Reliably Inform Human Studies?
van der Worp, H. B., Howells, D. W., Sena, E. S., Porritt, M. J., Rewell, S., O'Collins, V., & Macleod, M. R. (2010) · PLoS Medicine · doi:10.1371/journal.pmed.1000245 · Cited by 1,354
Update of the Stroke Therapy Academic Industry Roundtable Preclinical Recommendations
Fisher, M., Feuerstein, G., Howells, D. W., Hurn, P. D., Kent, T. A., Savitz, S. I., & Lo, E. H. (2009) · Stroke · doi:10.1161/strokeaha.108.541128 · Cited by 1,352
A call for transparent reporting to optimize the predictive value of preclinical research
Landis, S. C., Amara, S. G., Asadullah, K., Austin, C. P., Blumenstein, R., Bradley, E. W., Crystal, R. G., Darnell, R. B., Ferrante, R. J., Fillit, H., et al. (2012) · Nature · doi:10.1038/nature11556 · Cited by 1,196
Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke
Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., & Carmichael, S. T. (2010) · Nature · doi:10.1038/nature09511 · Cited by 869
Translation of Research Evidence From Animals to Humans
Hackam, D. G., & Redelmeier, D. A. (2006) · JAMA · doi:10.1001/jama.296.14.1731 · Cited by 733
Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention
Kumar, A., & Loane, D. J. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.06.008 · Cited by 710
NXY-059 for Acute Ischemic Stroke
Lees, K. R., Zivin, J. A., Ashwood, T., Davalos, A., Davis, S. M., Diener, H.-C., Grotta, J., Lyden, P., Shuaib, A., Hårdemark, H.-G., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa052980 · Cited by 660
Ischemic stroke: experimental models and reality
Sommer, C. J. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1667-0 · Cited by 599
Loane, D. J., & Faden, A. I. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.005 · Cited by 574
Animal models of focal and global cerebral ischemia
Traystman, R. J. (2003) · ILAR Journal · doi:10.1093/ilar.44.2.85 · Cited by 413
Risk of bias in reports of in vivo research: a focus for improvement
Macleod, M. R., Lawson McLean, A., Kyriakopoulou, A., Serghiou, S., de Wilde, A., Sherratt, N., Hirst, T., Hemblade, R., Bahor, Z., Nunes-Fonseca, C., et al. (2015) · PLOS Biology · doi:10.1371/journal.pbio.1002273 · Cited by 358
Good Laboratory Practice: Preventing Introduction of Bias at the Bench
Macleod, M. R., Fisher, M., O'Collins, V., Sena, E. S., Dirnagl, U., Bath, P. M. W., Buchan, A., van der Worp, H. B., Traystman, R., Minematsu, K., et al. (2009) · Stroke · doi:10.1161/strokeaha.108.525386 · Cited by 331
Asynchronous therapy restores motor control by rewiring of the rat corticospinal tract after stroke
Wahl, A. S., Omlor, W., Rubio, J. C., Chen, J. L., Zheng, H., Schröter, A., Gullo, M., Weinmann, O., Kobayashi, K., Helmchen, F., et al. (2014) · Science · doi:10.1126/science.1253050 · Cited by 322
Macleod, M. R., van der Worp, H. B., Sena, E. S., Howells, D. W., Dirnagl, U., & Donnan, G. A. (2008) · Stroke · doi:10.1161/strokeaha.108.515957 · Cited by 319
Howells, D. W., Porritt, M. J., Rewell, S. S., O'Collins, V., Sena, E. S., van der Worp, H. B., Traystman, R. J., & Macleod, M. R. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.66 · Cited by 309
Evaluation of excess significance bias in animal studies of neurological diseases
Tsilidis, K. K., Panagiotou, O. A., Sena, E. S., Aretouli, E., Evangelou, E., Howells, D. W., Salman, R. A.-S., Macleod, M. R., & Ioannidis, J. P. A. (2013) · PLoS Biology · doi:10.1371/journal.pbio.1001609 · Cited by 295
Macrae, I. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01398.x · Cited by 274
Future of neuroprotection for acute stroke: In the aftermath of the SAINT trials
Savitz, S. I., & Fisher, M. (2007) · Annals of Neurology · doi:10.1002/ana.21127 · Cited by 267
Neuroprotection for Ischaemic Stroke: Translation from the Bench to the Bedside
Sutherland, B. A., Minnerup, J., Balami, J. S., Arba, F., Buchan, A. M., & Kleinschnitz, C. (2012) · International Journal of Stroke · doi:10.1111/j.1747-4949.2012.00770.x · Cited by 259
Meta-analysis of preclinical studies of mesenchymal stromal cells for ischemic stroke
Vu, Q., Xie, K., Eckert, M., Zhao, W., & Cramer, S. C. (2014) · Neurology · doi:10.1212/wnl.0000000000000278 · Cited by 235
Replication and reproducibility in spinal cord injury research
Steward, O., Popovich, P. G., Dietrich, W. D., & Kleitman, N. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2011.06.017 · Cited by 186
Fisher, M. (2005) · Stroke · doi:10.1161/01.str.0000173403.60553.27 · Cited by 156
ElAli, A., Doeppner, T. R., Zechariah, A., & Hermann, D. M. (2011) · Stroke · doi:10.1161/strokeaha.111.615559 · Cited by 150
Kilic, E., Kilic, Ü., Bacigaluppi, M., Guo, Z., Abdallah, N. B., Wolfer, D. P., Reiter, R. J., Hermann, D. M., & Bassetti, C. L. (2008) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00568.x · Cited by 140
Ramirez, F. D., Motazedian, P., Jung, R. G., Di Santo, P., MacDonald, Z. D., Moreland, R., Simard, T., Clancy, A. A., Russo, J. J., Welch, V. A., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.310628 · Cited by 138
Bringing rigour to translational medicine
Howells, D. W., Sena, E. S., & Macleod, M. R. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.232 · Cited by 130
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
Decoding the Transcriptional Response to Ischemic Stroke in Young and Aged Mouse Brain
Androvic, P., Kirdajova, D., Tureckova, J., Zucha, D., Rohlova, E., Abaffy, P., Kriska, J., Valny, M., Anderova, M., Kubista, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107777 · Cited by 118
Systematic reviews of animal experiments demonstrate poor human clinical and toxicological utility
Knight, A. (2007) · Alternatives to Laboratory Animals · doi:10.1177/026119290703500610 · Cited by 105
A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol
Sultan, S. R., Millar, S. A., England, T. J., & O'Sullivan, S. E. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00081 · Cited by 95
Preclinical efficacy studies in investigator brochures: do they enable risk–benefit assessment?
Wieschowski, S., Chin, W. W. L., Federico, C., Sievers, S., Kimmelman, J., & Strech, D. (2018) · PLOS Biology · doi:10.1371/journal.pbio.2004879 · Cited by 70
Weaver, C. S., Leonardi-Bee, J., Bath-Hextall, F. J., & Bath, P. M. W. (2004) · Stroke · doi:10.1161/01.str.0000125010.70652.93 · Cited by 67
Pérez-Mato, M., Ramos-Cabrer, P., Sobrino, T., Blanco, M., Ruban, A., Mirelman, D., Menendez, P., Castillo, J., & Campos, F. (2014) · Cell Death & Disease · doi:10.1038/cddis.2013.507 · Cited by 66
Nitzsche, B., Frey, S., Collins, L. D., Seeger, J., Lobsien, D., Dreyer, A., Kirsten, H., Stoffel, M. H., Fonov, V. S., & Boltze, J. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00069 · Cited by 61
Balestrino, M., Sarocchi, M., Adriano, E., & Spallarossa, P. (2016) · Amino Acids · doi:10.1007/s00726-016-2173-8 · Cited by 60
Strategies to optimize the validity of disease models in the drug discovery process
Sams-Dodd, F. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.02.005 · Cited by 60
Cognitive recovery in the aged rat after stroke and anti-Nogo-A immunotherapy
Gillani, R. L., Tsai, S.-Y., Wallace, D. G., O’Brien, T. E., Arhebamen, E., Tole, M., Schwab, M. E., & Kartje, G. L. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.015 · Cited by 59
Rewell, S. S. J., Churilov, L., Sidon, T. K., Aleksoska, E., Cox, S. F., Macleod, M. R., & Howells, D. W. (2017) · PLOS ONE · doi:10.1371/journal.pone.0171688 · Cited by 54
Härtig, W., Mages, B., Aleithe, S., Nitzsche, B., Altmann, S., Barthel, H., Krueger, M., & Michalski, D. (2017) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2017.00015 · Cited by 53
Samsa, G. P., & Matchar, D. B. (2001) · Stroke · doi:10.1161/01.str.32.3.669 · Cited by 51
Warkentin, L. M., Auriat, A. M., Wowk, S., & Colbourne, F. (2010) · Brain Research · doi:10.1016/j.brainres.2009.10.058 · Cited by 50
Increasing value and reducing waste in stroke research
Berge, E., Salman, R. A.-S., van der Worp, H. B., Stapf, C., Sandercock, P., Sprigg, N., Macleod, M. R., Kelly, P. J., Nederkoorn, P. J., Ford, G. A., et al. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30078-9 · Cited by 41
Mendonça, B. P., Cardoso, J. D. S., Michels, M., Vieira, A. C., Wendhausen, D., Manfredini, A., Singer, M., Dal-Pizzol, F., & Dyson, A. (2020) · Intensive Care Medicine Experimental · doi:10.1186/s40635-020-00300-8 · Cited by 21
Hermann, D. M., Bacigaluppi, M., Bassetti, C. L., Bassotti, G., Boltze, J., Chan, A., Dalkara, T., Denes, A., Diez-Tejedor, E., Dodel, R., et al. (2025) · Exploration of Neuroscience · doi:10.37349/en.2025.1006106 · Cited by 13
Zhang, Y., Tan, J., Yang, K., Fan, W., Yu, B., & Shi, W. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02831-9 · Cited by 7
Modeling Risk Factors and Confounding Effects in Stroke
McColl, B., Howells, D., Rothwell, N., & Denes, A. (2010) · Neuromethods · doi:10.1007/978-1-60761-750-1_9 · Cited by 3
Martos, D., Lőrinczi, B., Szatmári, I., Vécsei, L., & Tanaka, M. (2025) · doi:10.20944/preprints202504.1511.v2 · Cited by 13
Metadata
- Venue
- Stroke
- Published
- 1999-12
- Volume
- 30
- Issue
- 12
- Pages
- 2752-2758
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2112646710
- Cited by
- 1,251
- References
- 2
- FWCI
- 14.54
- Type
- journal article
- Language
- en
- Open access
- bronze
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.