Contralesional axonal remodeling of the corticospinal system in adult rats after stroke and bone marrow stromal cell treatment
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Background and Purpose— Motor recovery after stroke is associated with neuronal reorganization in bilateral hemispheres. We investigated contralesional corticospinal tract remodeling in the brain and spinal cord in rats after stroke and treatment of bone marrow stromal cells. Methods— Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion. Phosphate-buffered saline or bone marrow stromal cells were injected into a tail vein 1 day postischemia. An adhesive removal test was performed weekly to monitor functional recovery. Threshold currents of intracortical microstimulation on the left motor cortex for evoking bilateral forelimb movements were measured 6 weeks after stroke. When intracortical microstimulation was completed, biotinylated dextran amine was injected into the left motor cortex to anterogradely label the corticospinal tract. At 4 days before euthanization, pseudorabies virus-152-EGFP and 614-mRFP were injected into left or right forelimb extensor muscles, respectively. All animals were euthanized 8 weeks after stroke. Results— In normal rats (n=5), the corticospinal tract showed a unilateral innervation pattern. In middle cerebral artery occlusion rats (n=8), our data demonstrated that: 1) stroke reduced the stimulation threshold evoking ipsilateral forelimb movement; 2) EGFP-positive pyramidal neurons were increased in the left intact cortex, which were labeled from the left stroke-impaired forelimb; and 3) biotinylated dextran amine-labeled contralesional axons sprouted into the denervated spinal cord. Bone marrow stromal cells significantly enhanced all 3 responses (n=8, P <0.05). Conclusions— Our data demonstrated that corticospinal tract fibers originating from the contralesional motor cortex sprout into the denervated spinal cord after stroke and bone marrow stromal cells treatment, which may contribute to functional recovery.
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Treatments promoting neurological recovery by remodelling brain tissue can be instituted during the stroke recovery phase, unlike neuroprotection which requires acute intervention.
“By contrast with neuroprotection, which requires an acute intervention, treatments promoting neurological recovery by remodelling of brain tissue can be instituted during the stroke recovery phase.10–15”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
Post-ischaemic endogenous plasticity partly compensates for loss of axons in target structures of damaged fibre bundles at various brain levels and spinal cord.
“Post-ischaemic endogenous plasticity partly compensates for the loss of axons in target structures of damaged fibre bundles at various levels of the brain (eg, red nucleus and facial nucleus) and spinal cord.12,19,24”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
The efficacy of neurorestorative therapies does not depend on successful reperfusion of ischaemic brain tissue, unlike neuroprotection.
“By sharp contrast with neuroprotection, the efficacy of neuro restorative therapies does not depend on the successful reperfusion of ischaemic brain tissue.11,12,15,17,21”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
Terminal axonal sprouting is enhanced in both ipsilesional and contralesional pyramidal tract systems.
“Terminal axonal sprouting is enhanced in both the ipsilesional19,24 and the contra lesional12,19 pyramidal tract system.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
This lesion-remote plasticity involves midline crossing of fibres from contralesional to ipsilesional hemisphere at the red nucleus and re-entry into contralesional hemicord at cervical spinal cord.
“This lesion-remote plasticity involves the midline crossing of fibres from the contralesional to the ipsilesional hemisphere at the level of the red nucleus10,17,19,24 and the re-entry of fibres into the contralesional hemicord at the level of the cervical spinal cord (figure 1).11,12,15”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
Homologous fibres from the contralesional motor cortex grow across the midline to reach denervated neurons in target structures of the lesioned pyramidal tract.
“Instead, homologous fibres originating from the contralesional motor cortex grow out across the midline to reach denervated neurons in target structures of the lesioned pyramidal tract (figure 1).10–12,15,17,19,24”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
Contralesional plasticity as a basis for neurological recovery occurs in several species, including rats, mice, and macaques.
“Contralesional plasticity as a basis for neurological recovery occurs in several species (eg, in rats,11,15,17 mice,12,19,24 and macaques32).”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [12]
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- Authors
- Liu, Z., Li, Y., Zhang, X., Savant-Bhonsale, S., & Chopp, M.
- Affiliations
- Oakland University (US)
- From the Department of Neurology (Z.L., Y.L., X.Z., M.C.), Henry Ford Hospital, Detroit, Mich; the Department of Physics (M.C.), Oakland University, Rochester, Mich; and Theradigm, Inc (S.S.-B.), Baltimore, Md.
- ORCID
- Venue
- Stroke
- Published
- 2008-09
- Volume
- 39
- Issue
- 9
- Pages
- 2571-2577
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- PMC
- PMC2593106
- OpenAlex
- W2136193279
- Cited by
- 115
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 8 · 2018: 4 · 2017: 9 · 2016: 10 · 2015: 5 · 2014: 14 · 2013: 9 · 2012: 13
- FWCI
- 7.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Princeton University
- National Institute of Neurological Disorders and Stroke (P01NS42345, P01NS042345)
- Topics
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- corticospinal tract, mesenchymal stem cells, motor recovery, middle cerebral artery occlusion, intracortical microstimulation, pseudorabies virus tracing, axonal remodeling
- MeSH terms
- Animals, Axonal Transport, Biotin, Brain Mapping, Dextrans, Disease Models, Animal, Electric Stimulation, Fluorescent Antibody Technique, Functional Laterality, Male, Motor Cortex, Nerve Regeneration, Neuronal Plasticity, Herpesvirus 1, Suid, Pyramidal Tracts, Bone Marrow Transplantation, Stromal Cells, Rats, Wistar, Muscle, Skeletal, Recovery of Function, Infarction, Middle Cerebral Artery, Brain Infarction, Stroke, Rats
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