Anatomical Correlates of Locomotor Recovery Following Dorsal and Ventral Lesions of the Rat Spinal Cord

Schucht, P.; Raineteau, Olivier; Schwab, Martin E.; Fouad, Karim

doi:10.1006/exnr.2002.7909

Cited by 280 publications

(239 citation statements)

References 44 publications

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“…Further investigations reported that spared white matter volume is the parameter correlating with functional outcome the most (McEwen and Springer, 2006;Schucht et al, 2002;You et al, 2003). This also holds true for mice of different genetic backgrounds (Hashimoto et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

Kim

Loy

Wang

et al. 2010

Journal of Neurotrauma

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Accurate diagnosis of spinal cord injury (SCI) severity must be achieved before highly aggressive experimental therapies can be tested responsibly in the early phases after trauma. These studies demonstrate for the first time that axial diffusivity (ljj), derived from diffusion tensor imaging (DTI) within 3 h after SCI, accurately predicts long-term locomotor behavioral recovery in mice. Female C57BL=6 mice underwent sham laminectomy or graded contusive spinal cord injuries at the T9 vertebral level (5 groups, n ¼ 8 for each group). In-vivo DTI examinations were performed immediately after SCI. Longitudinal measurements of hindlimb locomotor recovery were obtained using the Basso mouse scale (BMS). Injured and spared regions of ventrolateral white matter (VLWM) were reliably separated in the hyperacute phase by threshold segmentation. Measurements of ljj were compared with histology in the hyperacute phase and 14 days after injury. The spared normal VLWM determined by hyperacute ljj and 14-day histology correlated well (r ¼ 0.95). A strong correlation between hindlimb locomotor function recovery and ljj-determined spared normal VLWM was also observed. The odds of significant locomotor recovery increased by 18% with each 1% increase in normal VLWM measured in the hyperacute phase (odds ratio ¼ 1.18, p ¼ 0.037). The capability of measuring subclinical changes in spinal cord physiology and murine genetic advantages offer an early window into the basic mechanisms of SCI that was not previously possible. Although significant obstacles must still be overcome to derive similar data in human patients, the path to clinical translation is foreseeable and achievable.

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Section: Discussionmentioning

confidence: 99%

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

Kim

Loy

Wang

et al. 2010

Journal of Neurotrauma

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“…LWM axons including those in the reticulospinal tract play an important part in the control of hindlimb locomotion (Schucht et al, 2002), and we therefore focused on recovery of hindlimb motor function. Lateral hemisection of the thoracic spinal cord leads to transient severe impairment of hindlimb function ipsilateral to the injury (Hains et al, 2001;Ballermann and Fouad, 2006;Arvanian et al, 2009) with milder effects on the contralateral hindlimb.…”

Section: Effects On Behaviormentioning

confidence: 99%

“…These connections from LWM, including ventrolateral funiculus (VLF), are of particular interest because of their role in the control of locomotion (Schucht et al, 2002;Alstermark et al, 2004;Reed et al, 2008). Previous studies in newborn animals have shown that the strength of the excitatory synaptic connection from VLF axons to lumbar motoneurons can be enhanced by NT3 (Arvanian et al, 2003), but novel polysynaptic connections required to provide detours around lesions are not .…”

Section: Introductionmentioning

confidence: 99%

Chondroitinase ABC Combined with Neurotrophin NT-3 Secretion and NR2D Expression Promotes Axonal Plasticity and Functional Recovery in Rats with Lateral Hemisection of the Spinal Cord

García-Alías¹,

Petrosyan²,

Schnell³

et al. 2011

J. Neurosci.

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Elevating spinal levels of neurotrophin NT-3 (NT3) while increasing expression of the NR2D subunit of the NMDA receptor using a HSV viral construct promotes formation of novel multisynaptic projections from lateral white matter (LWM) axons to motoneurons in neonates. However, this treatment is ineffective after postnatal day 10. Because chondroitinase ABC (ChABC) treatment restores plasticity in the adult CNS, we have added ChABC to this treatment and applied the combination to adult rats receiving a left lateral hemisection (Hx) at T8. All hemisected animals initially dragged the ipsilateral hindpaw and displayed abnormal gait. Rats treated with ChABC or NT3/HSV-NR2D recovered partial hindlimb locomotor function, but animals receiving combined therapy displayed the most improved body stability and interlimb coordination [Basso-Beattie-Bresnahan (BBB) locomotor scale and gait analysis]. Electrical stimulation of the left LWM at T6 did not evoke any synaptic response in ipsilateral L5 motoneurons of control hemisected animals, indicating interruption of the white matter. Only animals with the full combination treatment recovered consistent multisynaptic responses in these motoneurons indicating formation of a detour pathway around the Hx. These physiological findings were supported by the observation of increased branching of both cut and intact LWM axons into the gray matter near the injury. ChABC-treated animals displayed more sprouting than control animals and those receiving NT3/HSV-NR2D; animals receiving the combination of all three treatments showed the most sprouting. Our results indicate that therapies aimed at increasing plasticity, promoting axon growth and modulating synaptic function have synergistic effects and promote better functional recovery than if applied individually.

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“…This localization is important because the descending tracts involved in locomotor recovery follow a precise distribution mainly in the anterior and lateral funiculi. 9,10 In addition, MRI-based measurements of lesion size, cord atrophy and spared matter may be more accurate than histological microscopy, despite the lower resolution of MRI, because of the absence of tissue deformation. This is underlined in this investigation by the observed variable ratios of histological to MRI measurements, indicating that the spinal cord undergoes changes during the preparation for histology, including retraction during the freezing process.…”

Section: Discussionmentioning

confidence: 99%

Post-mortem assessment of rat spinal cord injury and white matter sparing using inversion recovery-supported proton density magnetic resonance imaging

et al. 2010

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Study design:This was an experimental study. Objectives: White matter sparing influences locomotor recovery after traumatic spinal cord injury (SCI). The objective of the present post-mortem magnetic resonance imaging (MRI) investigation was to assess the potential of a simple inversion recovery (IR) sequence in combination with high-resolution proton density (PD) images to selectively depict spared white matter after experimental SCI in the rat. Setting: This study was conducted at University of Liège and Centre Hospitalier Universitaire, Liège, Belgium and Hasselt University, Diepenbeek, Belgium. Methods: Post-mortem 9.4 tesla (T) MRI was obtained from five excised rat spines 2 months after compressive SCI. The locomotor recovery had been followed weekly using the standardized Basso-Beattie-Bresnahan scale. IR MRI was used to depict normal white matter as very hypo-intense. Preserved white matter, cord atrophy and lesion volume were assessed, and histology was used to confirm MRI data. Results: MRI showed lesion severity and white matter sparing in accordance with the degree of locomotor recovery. IR MRI enhanced detection of spared and injured white matter by selectively altering the signal of spared white matter. Even subtle white matter changes could be detected, increasing diagnostic accuracy as compared to PD alone. MRI accuracy was confirmed by histology. Conclusion: High-resolution IR-supported PD MRI provides useful micro-anatomical information about white matter damage and sparing in the post-mortem assessment of chronic rat SCI.

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Anatomical Correlates of Locomotor Recovery Following Dorsal and Ventral Lesions of the Rat Spinal Cord

Cited by 280 publications

References 44 publications

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

Chondroitinase ABC Combined with Neurotrophin NT-3 Secretion and NR2D Expression Promotes Axonal Plasticity and Functional Recovery in Rats with Lateral Hemisection of the Spinal Cord

Post-mortem assessment of rat spinal cord injury and white matter sparing using inversion recovery-supported proton density magnetic resonance imaging

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