Multimodal Examination of Structural and Functional Remapping in the Mouse Photothrombotic Stroke Model
Open accessAbstract
Recent studies show a limited capacity for neural repair after stroke, which includes remapping of sensorimotor functions and sprouting of new connections. However, physiologic and connectional plasticity of sensory maps during long-term functional recovery in the mouse have not been determined. Using a photothrombotic stroke model, we targeted the motor cortex, which we show results in lasting behavioral deficits on the grid-walking and in the cylinder tasks out to 8 weeks after stroke. Mice recovered performance in a skilled reaching task, showing no deficit from week 2 after stroke. Long-term optical intrinsic signal imaging revealed functional reorganization of sensory cortical maps for both forelimb and hindlimb, with more diffuse sensory physiologic maps. There was a small but significant increase in motor neuron projections within the areas of functional cortical reorganization as assessed using the neuroanatomic tracer biotinylated dextran amine. These findings show that the sensorimotor cortex undergoes remapping of cortical functions and axonal sprouting within the same regions during recovery after stroke. This suggests a linked structural and physiologic plasticity underlying recovery. Combined long-term structural and functional mapping after stroke in the mouse is practical and provides a rich data set for mechanistic analysis of stroke recovery.
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Stroke normally produces a limited pattern of axonal sprouting from motor or somatosensory cortex posteriorly to areas adjacent to or caudal to the stroke.
“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 [28]
The Results report post-stroke sprouting in motor-to-premotor and motor-to-somatosensory connections, including a region of posterior motor and rostral somatosensory cortex (page not available). But they describe the sprouting as circumferential around motor cortex, not a normally limited pattern directed posteriorly to areas adjacent to or caudal to the stroke. (LLM, conf=0.86)
Experimental — accuracy not yet measuredStroke alone modestly but significantly induces axonal sprouting in the motor cortex adjacent to the stroke site compared to normal motor system connections.
“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 [28]
This experimental design has been validated by other groups conducting similar behavioral or tissue outcomes experiments.
“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 [28]
GDF10 gain and loss of function was produced directly from the stroke through sustained release via biopolymer hydrogel, which produces release over 2-3 weeks from the stroke site without altering local inflammation, gliosis, neuronal or vascular structure.
“To test this hypothesis, GDF10 gain and loss of function was produced directly from the stroke through sustained release via biopolymer hydrogel, which produces release over 2–3 weeks from the stroke site3,4,28 without altering local inflammation, gliosis, neuronal or vascular structure4.”
From GDF10 is a signal for axonal sprouting and functional recovery after stroke (2015) · cites this paper as [28]
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Experimental — accuracy not yet measuredSample size for in vivo quantitative cortical mapping studies was estimated from previous publications with similar mechanistic studies.
“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 [28]
Materials and Methods (Registration of Maps and Optical Intrinsic Signaling Imaging; page unavailable) reports five animals per group for cortical mapping. The Statistics section lists the analyses used, but neither it nor the mapping methods says that sample size was estimated from previous publications. Searched for sample-size estimation and spatial-correlation statistics. (LLM, conf=0.72)
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References 28 · Cited by 103
Research works printed but not linked: 1
- Paxinos G, Franklin KBJ. The mouse brain in stereotaxic coordinates. Elsevier Academic Press; 2004. [Google Scholar]
- Authors
- Clarkson, A. N., López-Valdés, H. E., Overman, J. J., Charles, A. C., Brennan, K., & Carmichael, S. T.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Carmichael, S Thomas
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2013-02-06
- Volume
- 33
- Issue
- 5
- Pages
- 716-723
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- PMC
- PMC3652691
- OpenAlex
- W2009779748
- Cited by
- 103
- References
- 28
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 1 · 2023: 7 · 2022: 8 · 2021: 13 · 2020: 7 · 2019: 11 · 2018: 4 · 2017: 8 · 2016: 6 · 2015: 14 · 2014: 8 · 2013: 5
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-08-08)
- Open access
- green
- europepmc.org
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (K08NS059072, R21NS070084)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Cognitive Neuroscience › Tactile and Sensory Interactions
- Keywords
- stroke recovery, sensorimotor cortex, cortical reorganization, functional reorganization, axonal sprouting, intrinsic signal imaging, motor cortex, sensory maps, mouse stroke model, neuroplasticity
- MeSH terms
- Animals, Brain, Disease Models, Animal, Male, Mice, Inbred C57BL, Motor Activity, Motor Cortex, Thrombosis, Walking, Stroke, Mice
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