Regulated gene activity is crucial to the formation and function of the nervous system. It is well known that gene regulation can occur at the transcriptional, post-transcriptional, translational, and post-translational levels. In this review our focus has been on the post-transcriptional regulation in neurons and on neural-specific RNA binding proteins that may be involved in post-transcriptional modulation of gene activity. We have taken advantage of this opportunity to review our work on the elav gene of Drosophila melanogaster which encodes a neural-specific RNA binding protein and relate it to other members of this elav-like gene family. We report new data that suggests that elav is post-transcriptionally regulated and we demonstrate that below-threshold levels of ELAV protein severely affects neuronal differentiation.

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Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Study design: Multi-center, prospective, cohort study. Objectives: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). Setting: Inpatient rehabilitation hospitals in the United States (US). Methods: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. Results: Total agreement between raters was above 70% on most SCIM III tasks and all k-coefficients were statistically significant (Po0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-a was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (Po0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (Po0.0001). Conclusion: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

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