Focal Stroke in the Developing Rat Motor Cortex Induces Age- and Experience-Dependent Maladaptive Plasticity of Corticospinal System

Overview

Journal Front Neural Circuits

Date 2017 Jul 15

PMID 28706475

Citations 10

Authors

Mariangela Gennaro

Alessandro Mattiello

Raffaele Mazziotti

Camilla Antonelli

Lisa Gherardini

Andrea Guzzetta

Nicoletta Berardi

Giovanni Cioni

Tommaso Pizzorusso

Affiliations

Soon will be listed here.

Abstract

Motor system development is characterized by an activity-dependent competition between ipsilateral and contralateral corticospinal tracts (CST). Clinical evidence suggests that age is crucial for developmental stroke outcome, with early lesions inducing a "maladaptive" strengthening of ipsilateral projections from the healthy hemisphere and worse motor impairment. Here, we investigated in developing rats the relation between lesion timing, motor outcome and CST remodeling pattern. We induced a focal ischemia into forelimb motor cortex (fM1) at two distinct pre-weaning ages: P14 and P21. We compared long-term motor outcome with changes in axonal sprouting of contralesional CST at red nucleus and spinal cord level using anterograde tracing. We found that P14 stroke caused a more severe long-term motor impairment than at P21, and induced a strong and aberrant contralesional CST sprouting onto denervated spinal cord and red nucleus. The mistargeted sprouting of CST, and the worse motor outcome of the P14 stroke rats were reversed by an early skilled motor training, underscoring the potential of early activity-dependent plasticity in modulating lesion outcome. Thus, changes in the mechanisms controlling CST plasticity occurring during the third postnatal week are associated with age-dependent regulation of the motor outcome after stroke.

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References

Graziadio S, Tomasevic L, Assenza G, Tecchio F, Eyre J . The myth of the 'unaffected' side after unilateral stroke: is reorganisation of the non-infarcted corticospinal system to re-establish balance the price for recovery?. Exp Neurol. 2012; 238(2):168-75. PMC: 3508413. DOI: 10.1016/j.expneurol.2012.08.031. View

Kirton A, deVeber G . Paediatric stroke: pressing issues and promising directions. Lancet Neurol. 2014; 14(1):92-102. DOI: 10.1016/S1474-4422(14)70227-3. View

Kubin L, Volgin D . Developmental profiles of neurotransmitter receptors in respiratory motor nuclei. Respir Physiol Neurobiol. 2008; 164(1-2):64-71. PMC: 2642898. DOI: 10.1016/j.resp.2008.04.012. View

Eyre J, Taylor J, Villagra F, Smith M, Miller S . Evidence of activity-dependent withdrawal of corticospinal projections during human development. Neurology. 2001; 57(9):1543-54. DOI: 10.1212/wnl.57.9.1543. View

Jones T, Allred R, Jefferson S, Kerr A, Woodie D, Cheng S . Motor system plasticity in stroke models: intrinsically use-dependent, unreliably useful. Stroke. 2013; 44(6 Suppl 1):S104-6. PMC: 3727618. DOI: 10.1161/STROKEAHA.111.000037. View

Canty A, Murphy M . Molecular mechanisms of axon guidance in the developing corticospinal tract. Prog Neurobiol. 2008; 85(2):214-35. DOI: 10.1016/j.pneurobio.2008.02.001. View

Hutson T, Verhaagen J, Yanez-Munoz R, Moon L . Corticospinal tract transduction: a comparison of seven adeno-associated viral vector serotypes and a non-integrating lentiviral vector. Gene Ther. 2011; 19(1):49-60. PMC: 3160493. DOI: 10.1038/gt.2011.71. View

Raffin E, Dyrby T . Diagnostic approach to functional recovery: diffusion-weighted imaging and tractography. Front Neurol Neurosci. 2013; 32:26-35. DOI: 10.1159/000348818. View

Goulding M . Circuits controlling vertebrate locomotion: moving in a new direction. Nat Rev Neurosci. 2009; 10(7):507-18. PMC: 2847453. DOI: 10.1038/nrn2608. View

10.

Joosten E, Bar D . Axon guidance of outgrowing corticospinal fibres in the rat. J Anat. 1999; 194 ( Pt 1):15-32. PMC: 1467890. DOI: 10.1046/j.1469-7580.1999.19410015.x. View

11.

Friel K, Chakrabarty S, Kuo H, Martin J . Using motor behavior during an early critical period to restore skilled limb movement after damage to the corticospinal system during development. J Neurosci. 2012; 32(27):9265-76. PMC: 3422625. DOI: 10.1523/JNEUROSCI.1198-12.2012. View

12.

Reitmeir R, Kilic E, Kilic U, Bacigaluppi M, ElAli A, Salani G . Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity. Brain. 2010; 134(Pt 1):84-99. DOI: 10.1093/brain/awq344. View

13.

Kuo H, Ferre C, Carmel J, Gowatsky J, Stanford A, Rowny S . Using diffusion tensor imaging to identify corticospinal tract projection patterns in children with unilateral spastic cerebral palsy. Dev Med Child Neurol. 2016; 59(1):65-71. PMC: 5215687. DOI: 10.1111/dmcn.13192. View

14.

Arlotta P, Molyneaux B, Chen J, Inoue J, Kominami R, Macklis J . Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron. 2005; 45(2):207-21. DOI: 10.1016/j.neuron.2004.12.036. View

15.

Lee K, Kim J, Choi D, Lee J . Effect of task-specific training on functional recovery and corticospinal tract plasticity after stroke. Restor Neurol Neurosci. 2013; 31(6):773-85. DOI: 10.3233/RNN-130336. View

16.

Chakrabarty S, Friel K, Martin J . Activity-dependent plasticity improves M1 motor representation and corticospinal tract connectivity. J Neurophysiol. 2008; 101(3):1283-93. PMC: 2666405. DOI: 10.1152/jn.91026.2008. View

17.

de Medinaceli L, Freed W, Wyatt R . An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Exp Neurol. 1982; 77(3):634-43. DOI: 10.1016/0014-4886(82)90234-5. View

18.

Murphy T, Corbett D . Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci. 2009; 10(12):861-72. DOI: 10.1038/nrn2735. View

19.

Lodato S, Molyneaux B, Zuccaro E, Goff L, Chen H, Yuan W . Gene co-regulation by Fezf2 selects neurotransmitter identity and connectivity of corticospinal neurons. Nat Neurosci. 2014; 17(8):1046-54. PMC: 4188416. DOI: 10.1038/nn.3757. View

20.

Wahl A, Schwab M . Finding an optimal rehabilitation paradigm after stroke: enhancing fiber growth and training of the brain at the right moment. Front Hum Neurosci. 2014; 8:381. PMC: 4072965. DOI: 10.3389/fnhum.2014.00381. View