Induction of neuronal and inducible nitric oxide synthase in the motoneurons of spinal cord following transient abdominal aorta occlusion in rats.

BACKGROUND

Motoneurons in the spinal cord are especially vulnerable to ischemic injury and selectively destroyed after transient ischemia. Nitric oxide (NO) has been implicated in both neurodegneration and neuroprotection to ischemic insult. To evaluate the role of NO in pathophysiology to spinal cord ischemia, the expression of neuronal and inducible nitric oxide synthase (n-NOS and i-NOS) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the motoneurons of the lumbosacral spinal cord was examined in a rat model with transient abdominal aorta (TAA) occlusion.

MATERIALS AND METHODS

Male Sprague-Dawley rats were divided into sham-operated (n = 12) and TAA occlusion (n = 24) groups. TAA occlusion was induced by placement of a microvascular clamp around the abdominal aorta for 20 min. Three sham-operated and six TAA occlusion animals were sacrificed at each time interval at 4, 24, and 48 h and 7 days after operation. Tissue sections obtained from the lumbosacral spinal cord were processed for n-NOS, i-NOS, NADPH-d, and hematoxylin-eosin (HE) staining. Histological changes of motoneurons in ventral horn were assessed by HE staining.

RESULTS

In sham-operated control animals, n-NOS-, i-NOS-, and NADPH-d-positive neurons were barely detectable in the ventral horn of the spinal cord. At 4 h after TTA occlusion, n-NOS and NADPH-d expression became evident in the motoneurons and was markedly enhanced at 24 and 48 h. i-NOS expression was also induced in the ventral horn motoneurons of the lumbosacral spinal cord at the same time points. Enzymatic expression in the motoneurons was diminished 7 days after operation. Hyperchromatic neurons indicative of cell death were observed in HE-stained specimens 7 days following TAA occlusion.

CONCLUSIONS

The rapid induction of n-NOS, i-NOS, and NADPH-d in the motoneurons of ventral horn suggests that NO may be involved in the selective and delayed neuronal death in the spinal cord to the ischemic insult.