ABSTRACT
Acute spinal cord injury (SCI) is two-step process that first involves the primary mechanical injury and then the secondary injury is induced by various biochemical reactions. Apoptosis is one of secondary SCI mechanisms and it is thought to play an important role for the delayed neuronal injury. The enhanced formation of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of apoptosis in SCI. The level of .iNOS mRNA peaked at 6 hr after SCI and it declined until 72 hr after SCI in a rat model. Double-immunofluorescence staining revealed that iNOS positive cells were stained for ED-1, synaptophysin, GFAP, and oligodendrocyte marker. The terminal deoxynucleotidyl-transferase-mediated dUDP-biotin nick end-labeling (TUNEL) positive cell count was higher for the 72 hr post-SCI group than for the 24 hr post-SCI group. This cell count was also higher going in the caudal direction than in the rostral direction from the epicenter, and especially for the 72 hr group. Treatment with a selective iNOS inhibitor resulted in the reduction of TUNEL-positive cells at the lesion site. These findings suggest that nitric oxide generated by the iNOS of macrophages, neurons, oligodentrocytes, and astrocytes plays an important role for the acute secondary SCI that results from apoptotic cell death.
Subject(s)
Animals , Rats , Analysis of Variance , Apoptosis , Comparative Study , Glial Fibrillary Acidic Protein/analysis , In Situ Nick-End Labeling , Microscopy, Fluorescence , RNA, Messenger/genetics , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spinal Cord/chemistry , Spinal Cord Injuries/enzymology , Time FactorsABSTRACT
Injury to spinal cord was produced in rats by the clip compression technique by placing the aneurysm clip extradurally for 30 seconds. The traumatised spinal segment and the adjoining upper segment were used for biochemical estimations. Motor function of the injured rats was evaluated using the inclined plane. Phospholipid phosphorus values were significantly decreased in the injured spinal segment at 24 hrs. AchE activity was also decreased in the traumatised segment one week after injury. Dexamethasone and verapamil reversed the changes in AchE activity at the end of one week. At the one week assessment period, aneurysm clipped rats showed a decrease in the maximum angle in the inclined plane. Dexamethasone and verapamil treated rats showed improvement in the neurologic function, neurologic recovery was better in the dexamethasone treated group.