Quantitative study of neurofilament-positive fiber length in rat spinal cord lesions using isotropic virtual planes

Euler, Mia von; Larsen, Jacob Norvig; Janson, Ann Marie

doi:10.1002/(sici)1096-9861(19981102)400:4<441::aid-cne1>3.0.co;2-a

Cited by 10 publications

(2 citation statements)

References 33 publications

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“…Serotonergic fiber length was quantified using the Isotropic Virtual Planes (IVP) probe of StereoInvestigator [33]. A 500 µm long contour was drawn from the caudal edge of the lesion epicenter.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery

et al. 2009

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BackgroundHuman central nervous system-stem cells grown as neurospheres (hCNS-SCns) self-renew, are multipotent, and have potential therapeutic applications following trauma to the spinal cord. We have previously shown locomotor recovery in immunodeficient mice that received a moderate contusion spinal cord injury (SCI) and hCNS-SCns transplantation 9 days post-injury (dpi). Engrafted hCNS-SCns exhibited terminal differentiation to myelinating oligodendrocytes and synapse-forming neurons. Further, selective ablation of human cells using Diphtheria toxin (DT) abolished locomotor recovery in this paradigm, suggesting integration of human cells within the mouse host as a possible mechanism for the locomotor improvement. However, the hypothesis that hCNS-SCns could alter the host microenvironment as an additional or alternative mechanism of recovery remained unexplored; we tested that hypothesis in the present study.Methods and FindingsStereological quantification of human cells using a human-specific cytoplasmic marker demonstrated successful cell engraftment, survival, migration and limited proliferation in all hCNS-SCns transplanted animals. DT administration at 16 weeks post-transplant ablated 80.5% of hCNS-SCns. Stereological quantification for lesion volume, tissue sparing, descending serotonergic host fiber sprouting, chondroitin sulfate proteoglycan deposition, glial scarring, and angiogenesis demonstrated no evidence of host modification within the mouse spinal cord as a result of hCNS-SCns transplantation. Biochemical analyses supplemented stereological data supporting the absence of neural stem-cell mediated host repair. However, linear regression analysis of the number of engrafted hCNS-SCns vs. the number of errors on a horizontal ladder beam task revealed a strong correlation between these variables (r = −0.78, p<0.05), suggesting that survival and engraftment were directly related to a quantitative measure of recovery.ConclusionsAltogether, the data suggest that the locomotor improvements associated with hCNS-SCns transplantation were not due to modifications within the host microenvironment, supporting the hypothesis that human cell integration within the host circuitry mediates functional recovery following a 9 day delayed transplant.

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Section: Methodsmentioning

confidence: 99%

Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery

et al. 2009

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“…Serotonin fibers were quantified using Isotropic Virtual Planes in Stereoinvestigator (Microbrightfield, Williston, VT, USA; von Euler et al ., 1998). The counting area was determined by drawing a line across the tissue at the caudal end of the injury epicenter and drawing a second line 500 µm caudal to the first.…”

Section: Methodsmentioning

confidence: 99%

Wheel running following spinal cord injury improves locomotor recovery and stimulates serotonergic fiber growth

Engesser-Cesar

Ichiyama

Nefas

et al. 2007

Eur J of Neuroscience

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Exercise, through manual step training, robotic step training or voluntary wheel running, is emerging as a promising therapy after spinal cord injury (SCI). Animal models provide a tool to investigate the mechanisms by which physical activity influences recovery from SCI. In the present study, we extend previous experiments showing improved recovery after SCI with both pre- and post-injury running in a flat-surface running wheel and investigate mechanisms of recovery. We tested a clinically relevant model using post-injury wheel running, in which we provided mice with access to wheels either 3 days or 7 days/week. Open field behavior, observed for 15 weeks following moderate T9 contusion injury, showed a significant linear increase in locomotor improvements across groups, sedentary, 3-day runners and 7-day runners. Kinematic analysis of treadmill walking revealed that both wheel-running groups, 3 and 7 days/week, improved stepping ability compared with sedentary controls. Stereological quantification of neuron number in the injured segment of the spinal cord revealed no differences between the groups. However, stereological quantification of serotonin immunostaining using isotropic virtual planes showed increases in serotonin fiber length caudal to the lesion in the running groups. These observations suggest that improvement in function may be related to changes in serotonin fibers immediately caudal to the injury epicenter.

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Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression‐injury in adult rats

Poirrier

Nyssen

Scholtes

et al. 2003

J of Neuroscience Research

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Electromagnetic fields are able to promote axonal regeneration in vitro and in vivo. Repetitive transcranial magnetic stimulation (rTMS) is used routinely in neuropsychiatric conditions and as an atraumatic method to activate descending motor pathways. After spinal cord injury, these pathways are disconnected from the spinal locomotor generator, resulting in most of the functional deficit. We have applied daily 10 Hz rTMS for 8 weeks immediately after an incomplete high (T4-5; n = 5) or low (T10-11; n = 6) thoracic closed spinal cord compression-injury in adult rats, using 6 high- and 6 low-lesioned non-stimulated animals as controls. Functional recovery of hindlimbs was assessed using the BBB locomotor rating scale. In the control group, the BBB score was significantly better from the 7th week post-injury in animals lesioned at T4-5 compared to those lesioned at T10-11. rTMS significantly improved locomotor recovery in T10-11-injured rats, but not in rats with a high thoracic injury. In rTMS-treated rats, there was significant positive correlation between final BBB score and grey matter density of serotonergic fibres in the spinal segment just caudal to the lesion. We propose that low thoracic lesions produce a greater functional deficit because they interfere with the locomotor centre and that rTMS is beneficial in such lesions because it activates this central pattern generator, presumably via descending serotonin pathways. The benefits of rTMS shown here suggest strongly that this non-invasive intervention strategy merits consideration for clinical trials in human paraplegics with low spinal cord lesions.

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Quantitative study of neurofilament-positive fiber length in rat spinal cord lesions using isotropic virtual planes

Cited by 10 publications

References 33 publications

Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery

Analysis of Host-Mediated Repair Mechanisms after Human CNS-Stem Cell Transplantation for Spinal Cord Injury: Correlation of Engraftment with Recovery

Wheel running following spinal cord injury improves locomotor recovery and stimulates serotonergic fiber growth

Repetitive transcranial magnetic stimulation improves open field locomotor recovery after low but not high thoracic spinal cord compression‐injury in adult rats

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