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At least 973 records · Page 54Linked to original sources
PubMed2002

DNA microarray analysis of the contused spinal cord: effect of NMDA receptor inhibition.

Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate [MK-801]) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome.

Animals↗
PubMed1996

Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection.

Injury reproducibility is an important characteristic of experimental models of spinal cord injuries (SCI) because it limits the variability in locomotor and anatomical outcome measures. Recently, a more sensitive locomotor rating scale, the Basso, Beattie, and Bresnahan scale (BBB), was developed but had not been tested on rats with severe SCI complete transection. Rats had a 10-g rod dropped from heights of 6.25, 12.5, 25, and 50 mm onto the exposed cord at Tl 0 using the NYU device. A subset of rats with 25 and 50 mm SCI had subsequent spinal cord transection (SCI + TX) and were compared to rats with transection only (TX) in order to ascertain the dependence of recovery on descending systems. After 7-9 weeks of locomotor testing, the percentage of white matter measured from myelin-stained cross sections through the lesion center was significantly different between all the groups with the exception of 12.5 vs 25 mm and 25 vs 50 mm groups. Locomotor recovery was greatest for the 6.25-mm group and least for the 50-mm group and was correlated positively to the amount of tissue sparing at the lesion center (p < 0.0001). BBB scale sensitivity was sufficient to discriminate significant locomotor differences between the most severe SCI (50 mm) and complete TX (p < 0.01). Transection following SCI resulted in a drop in locomotor scores and rats were unable to step or support weight with their hindlimbs (p < 0.01), suggesting that locomotor recovery depends on spared descending systems. The SCI + TX group had a significantly greater frequency of HL movements during open field testing than the TX group (p < 0.005). There was also a trend for the SCI + TX group to have higher locomotor scores than the TX group (p > 0.05). Thus, spared descending systems appear to modify segmental systems which produce greater behavioral improvements than isolated cord systems.

Animals↗
PubMed1977

Serotonin in contused spinal cord.

An intensive experimental spinal cord impact trauma in rabbits led, after 90 minutes, to a significant increase of serotonin content in the segments of spinal cord at the injury epicentres. Adjacent segments showed normal values. It is suggested that the existing contradictory published data concerning the serotonin concentration in a traumatized spinal cord are accounted for by differences between animal species, the method of analysis used, and the technique employed in causing the injury. Potential involvement of serotonin in the autodestructive process is discussed.

Animals↗