ABSTRACT All attempts at treating strokes by pharmacologically reducing the human brain’s vulnerability to ischaemia have failed, leaving stroke as a leading cause of death, disability and

massive socioeconomic loss worldwide1. Over decades, research has failed to translate over 1,000 experimental treatments from discovery in cells and rodents to use in humans2,3,4, a

scientific crisis that gave rise to the prevailing belief that pharmacological neuroprotection is not feasible or practicable in higher-order brains. To provide a strategy for advancing

stroke therapy, we used higher-order gyrencephalic non-human primates, which bear genetic, anatomical and behavioural similarities to humans5,6 and tested neuroprotection by PSD-95

histology, preserved the capacity of ischaemic cells to maintain gene transcription in genome-wide screens of ischaemic brain tissue, and significantly preserved neurological function in

neurobehavioural assays. The degree of tissue neuroprotection by magnetic resonance imaging corresponded strongly to the preservation of neurological function, supporting the intuitive but

unproven dictum that integrity of brain tissue can reflect functional outcome. Our findings establish that tissue neuroprotection and improved functional outcome after stroke is

unequivocally achievable in gyrencephalic non-human primates treated with PSD-95 inhibitors. Efforts must ensue to translate these findings to humans. Access through your institution Buy or

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A CLINICALLY RELEVANT MODEL OF FOCAL EMBOLIC CEREBRAL ISCHEMIA BY THROMBUS AND THROMBOLYSIS IN RHESUS MONKEYS Article 27 June 2022 THE NEUROPROTECTIVE MECHANISM OF LITHIUM AFTER ISCHAEMIC

STROKE Article Open access 03 February 2022 ABERRANT NEURONAL EXCITATION PROMOTES NEUROINFLAMMATION IN THE PRIMARY MOTOR CORTEX OF ISCHEMIC STROKE MICE Article 12 March 2025 ACCESSION CODES

PRIMARY ACCESSIONS GENE EXPRESSION OMNIBUS * GSE35589 DATA DEPOSITS Microarray data are deposited in National Center for Biotechnology Information (NCBI) Gene Expression Omnibus under

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species. _Neurodegeneration_ 5, 275–286 (1996) Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS This work was supported by grants to M.T. from the Canadian Stroke Network

and the Heart and Stroke Foundation of Ontario, grant NA 6988. D.J.C. is a recipient of a Canadian Stroke Network postdoctoral research fellowship. M.T. is a Canada Research Chair (Tier 1)

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AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Toronto Western Hospital Research Institute, Toronto, Ontario, 2S8, M5T, Canada Douglas J. Cook, Lucy Teves & Michael Tymianski * Department

of Physiology, University of Toronto, Toronto, Ontario, M5S 1A8, Canada, Michael Tymianski * Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada, Michael

Tymianski * Department of Surgery, University of Toronto, Toronto, Ontario, M5S 1A8, Canada, Michael Tymianski Authors * Douglas J. Cook View author publications You can also search for this

author inPubMed Google Scholar * Lucy Teves View author publications You can also search for this author inPubMed Google Scholar * Michael Tymianski View author publications You can also

search for this author inPubMed Google Scholar CONTRIBUTIONS D.C. and M.T. performed the experimental procedures, collected and analysed the data and drafted the manuscript. L.T. performed

experimental procedures and data collection. CORRESPONDING AUTHOR Correspondence to Michael Tymianski. ETHICS DECLARATIONS COMPETING INTERESTS M.T. is president of NoNO Inc., a biotechnology

company founded to develop PSD-95 inhibitors discovered in his research laboratory. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary Figures 1-6 with

legends, Supplementary Methods, a Supplementary Discussion, Supplementary Tables 1-4 and Supplementary References. (PDF 5966 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT

SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Cook, D., Teves, L. &

Tymianski, M. Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. _Nature_ 483, 213–217 (2012). https://doi.org/10.1038/nature10841 Download citation * Received:

21 November 2011 * Accepted: 11 January 2012 * Published: 29 February 2012 * Issue Date: 08 March 2012 * DOI: https://doi.org/10.1038/nature10841 SHARE THIS ARTICLE Anyone you share the

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