The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
AMPA Receptor-Induced Local Brain-Derived Neurotrophic Factor Signaling Mediates Motor Recovery after Stroke
Open accessAbstract
Stroke is the leading cause of adult disability. Recovery after stroke shares similar molecular and cellular properties with learning and memory. A main component of learning-induced plasticity involves signaling through AMPA receptors (AMPARs). We systematically tested the role of AMPAR function in motor recovery in a mouse model of focal stroke. AMPAR function controls functional recovery beginning 5 d after the stroke. Positive allosteric modulators of AMPARs enhance recovery of limb control when administered after a delay from the stroke. Conversely, AMPAR antagonists impair motor recovery. The contributions of AMPARs to recovery are mediated by release of brain-derived neurotrophic factor (BDNF) in periinfarct cortex, as blocking local BDNF function in periinfarct cortex blocks AMPAR-mediated recovery and prevents the normal pattern of motor recovery. In contrast to a delayed AMPAR role in motor recovery, early administration of AMPAR agonists after stroke increases stroke damage. These findings indicate that the role of glutamate signaling through the AMPAR changes over time in stroke: early potentiation of AMPAR signaling worsens stroke damage, whereas later potentiation of the same signaling system improves functional recovery.
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“As reported previously3,4,28,29, stroke alone modestly but significantly induces axonal sprouting in the motor cortex adjacent to the stroke site compared to normal motor system connections (Supplementary Fig. 6b).”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [29]
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In the citing paper
“Stroke normally produces a limited pattern of axonal sprouting from motor or somatosensory cortex posteriorly to areas adjacent to or caudal to the stroke2–4,28,29.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [29]
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“Animal number in in vivo quantitative cortical mapping studies utilizes spatial correlation statistics, so sample size was estimated from previous publications with similar mechanistic studies3,4,28,29.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [29]
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“This biopolymer hydrogel releases both small and large molecules over a 3 week period from the infarct core3,4,29.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [29]
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“This experimental design has been validated by other groups conducting similar behavioral4 or tissue outcomes experiments3,4,28,29.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [29]
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“AMPA receptor antagonists impair neurological outcome, as does blockade of BDNF by TrkB-Fc-impregnated hydrogel.75”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [75]
In the citing paper
“Subsequent to ischaemic stroke, AMPA receptor activation by pharmacological allosteric modulators evokes the release of BDNF in the peri-infarct cortex, thus enhancing motor recovery.75”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [75]
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Citations
Cites
A synaptic model of memory: long-term potentiation in the hippocampus
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Lipton, P. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.4.1431 · Cited by 3,043
Motor learning: its relevance to stroke recovery and neurorehabilitation
Krakauer, J. W. (2006) · Current Opinion in Neurology · doi:10.1097/01.wco.0000200544.29915.cc · Cited by 1,282
A Neurovascular Niche for Neurogenesis after Stroke
Ohab, J. J., Fleming, S., Blesch, A., & Carmichael, S. T. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4323-06.2006 · Cited by 878 · cited 5×
“AMPAR activation also induces brainderived neurotrophic factor (BDNF) (Jourdi et al., 2009), a neurotrophin that is essential for neuronal remodeling and LTP (Bramham, 2008).”
BackgroundMethodInfluentialSelf-citationReducing 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
Self-citationNon-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke?
Hummel, F., & Cohen, L. (2006) · Lancet Neurology · doi:10.1016/s1474-4422(06)70525-7 · Cited by 858
Cheeran, B., Talelli, P., Mori, F., Koch, G., Suppa, A., Edwards, M. J., Houlden, H., Bhatia, K. P., Greenwood, R., & Rothwell, J. C. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159905 · Cited by 746
Strategies for stroke rehabilitation
Dobkin, B. H. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00851-8 · Cited by 732
Regulatory mechanisms of AMPA receptors in synaptic plasticity
Derkach, V. A., Oh, M. C., Guire, E. S., & Soderling, T. R. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2055 · Cited by 708
Extensive Cortical Rewiring after Brain Injury
Dancause, N., Barbay, S., Frost, S. B., Plautz, E. J., Chen, D., Zoubina, E. V., Stowe, A. M., & Nudo, R. J. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3256-05.2005 · Cited by 704
Cited by
Sorted by citations
Neuroplasticity Subserving Motor Skill Learning
Dayan, E., & Cohen, L. G. (2011) · Neuron · doi:10.1016/j.neuron.2011.10.008 · Cited by 1,408
Bernhardt, J. A., Hayward, K. S., Kwakkel, G., Ward, N., Wolf, S. L., Borschmann, K., Krakauer, J. W., Boyd, L. A., Carmichael, S. T., Corbett, D., et al. (2017) · International Journal of Stroke · doi:10.1177/1747493017711816 · Cited by 1,242
Self-citationGetting Neurorehabilitation Right: What Can Be Learned From Animal Models?
Krakauer, J. W., Carmichael, S. T., Corbett, D., & Wittenberg, G. F. (2012) · Neurorehabilitation and Neural Repair · doi:10.1177/1545968312440745 · Cited by 591
Self-citationNovel Stroke Therapeutics: Unraveling Stroke Pathophysiology and Its Impact on Clinical Treatments
George, P. M., & Steinberg, G. K. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.041 · Cited by 404
CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury
Joy, M. T., Ben Assayag, E., Shabashov-Stone, D., Liraz-Zaltsman, S., Mazzitelli, J., Arenas, M., Abduljawad, N., Kliper, E., Korczyn, A. D., Thareja, N. S., et al. (2019) · Cell · doi:10.1016/j.cell.2019.01.044 · Cited by 389
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Metadata
- Authors
- Clarkson, A. N., Overman, J. J., Zhong, S., Mueller, R., Lynch, G., & Carmichael, S. T.
- Affiliations
- University of California, Los Angeles (US)
- Cortex Pharmaceuticals (United States) (US)
- University of California, Irvine (US)
- Corresponding author
- Carmichael, S. Thomas
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-09
- Volume
- 31
- Issue
- 10
- Pages
- 3766-3775
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4698878
- OpenAlex
- W2096236127
- Cited by
- 276
- References
- 43
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 20 · 2023: 19 · 2022: 14 · 2021: 19 · 2020: 24 · 2019: 15 · 2018: 22 · 2017: 21 · 2016: 16 · 2015: 17 · 2014: 24 · 2013: 21 · 2012: 13
- FWCI
- 20.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Heart Association
- Larry L. Hillblom Foundation
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Health Research Council of New Zealand
- National Institute of Neurological Disorders and Stroke (R01NS045729, R01NS085019)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Keywords
- AMPA receptors, brain-derived neurotrophic factor, motor recovery, stroke, focal ischemic stroke, glutamate signaling, positive allosteric modulators, limb function
- MeSH terms
- Analysis of Variance, Animals, Cerebral Cortex, Electrophysiology, Enzyme-Linked Immunosorbent Assay, Male, Mice, Inbred C57BL, Motor Skills, Blotting, Western, Signal Transduction, Receptors, AMPA, Excitatory Amino Acid Agonists, Brain-Derived Neurotrophic Factor, Recovery of Function, Rats, Long-Evans, Stroke, Mice, Rats
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