Neuronal Loss and Expression of Neurotrophic Factors in a Model of Rat Chronic Compressive Spinal Cord Injury

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Abstract

Study Design.

An experimental animal study about neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords.

Objectives.

To investigate neuronal loss and the expression of neurotrophic factors in the chronic compressive spinal cords of rats, and to evaluate effects of decompressive procedures for the neuronal loss.

Summary of Background Data.

Chronic compression of spinal cords induces the loss of motor neurons in the anterior horn. However, the precise mechanism of this neuronal loss is not still understood completely. Furthermore, it is uncertain whether decompressive procedures prevent this neuronal loss or not.

Methods.

A thin expanding polymer sheet was implanted microsurgically underneath T7 laminae of rats. After 6, 9, 12, and 15 weeks, the thoracic spinal cord was harvested and examined histopathologically. The expression of neurotrophic factors, including NGF, BDNF, NT-3, GDNF, CNTF, and VEGF, was analyzed using semiquantitative RT-PCR, enzyme immunoassay, and immunohistochemistry. Decompressive surgery was performed through the removal of T7 laminae and the compression materials 6, 9, and 12 weeks after starting compression. Three weeks later, respectively, the neuronal loss in the anterior horn was estimated.

Results.

The spinal cords were progressively flattened by the expanding of the implanted polymer sheet, and the number of motor neurons in the anterior horn decreased, especially from 6 to 9 weeks after starting compression. Semiquantitative RT-PCR analysis showed that the expression of NGF and BDNF mRNAs was decreased significantly in the spinal cords of 12-week compression group compared with the 6-week compression group and that NGF mRNA expression was up-regulated significantly in the 6-week compression group relative to the 6-week control group. Any changes of expression of other neurotrophic factors were not significant. Since BDNF, not NGF, has been known to be one of the powerful survival factors for spinal motoneurons, we investigated the levels of BDNF protein in the compressive spinal cords using enzyme immunoassay and immunohistochemistry. We demonstrated the level of BDNF protein in the compressive spinal cords was increased 6 weeks after compression but declined after 12 weeks. The decompressive procedure inthe 6 weeks after compression prevented neuronal loss, but the same procedure in the 9 or 12 weeks was ineffective.

Conclusions.

From the point of view of neuronal loss, decompressive surgery at an earlier stage, when compensatory mechanisms including the up-regulation of BDNF might be still effective, could provide better therapeutic results against chronic mechanical compressive spinal cord lesions.

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