Changes in Nitric Oxide and Expression of Nitric Oxide Synthase in Spinal Cord after Acute Traumatic Injury in Rats

Abstract

The aim of this study was to observe the time course of NO production and NOS expression in the spinal cord following acute traumatic injury. Rat spinal cord was injured by extradural static weight-compression, which resulted in an incomplete transverse spinal cord lesion with paralysis of the lower extremities. Using this model, measurement of NO by microdialysis and Griess reaction and histological and immunohistochemical examinations using polyclonal antibodies to nNOS and iNOS were performed from immediately to 14 days after injury. In injured cord, the amount of NO markedly increased immediately after injury and gradually decreased between 1 and 12 h after injury. A second wave of increase in NO level was observed at 24 h and 3 days after injury. Histologically, hematomas and necrotic changes were observed after injury and demyelination of nerve fibers increased with time in the compressed segment. Immunohistochemically, the number of cells with expression of nNOS was increased immediately to 12 h after injury. Expression of iNOS was observed from 12 h to 3 days after injury. These findings suggested that the initial maximal increase of NO production might be caused mainly by nNOS and that the second wave of increase in NO might be due mainly to iNOS.

Significant correlation between cerebrospinal fluid nitric oxide concentrations and neurologic prognosis in incomplete cervical cord injury

“…Xu and co-workers reported a progressive increase in iNOS expression in the injured spinal cord with maximal expression on day 7, and that the high levels of iNOS expression persist for 2 weeks after SCI [33]. Nakahara reported that NO increases with biphasic changes, such as 1-12 and 24 h to 3 days after injury [28]. These animal studies support the finding that NO metabolites in the CSF increase from 1 day to 2 weeks after SCI, even in human.…”

“…In animal experiments of SCI, inducible NO synthase (iNOS) is expressed in the spinal cord immediately after SCI, reaches a maximal value at 12 h, and is maintained at this level of expression for 1 week [13,28,33]. Excessive NO production derived from iNOS has cytotoxic effects [5] and induces neuronal apoptosis, causing neural degeneration and neurodysfunction [1,9].…”

Post-traumatic inflammation following spinal cord injury

“…54 Immediately following contusion SCI, concentrations of NO markedly increase and then gradually decrease between 1 and 12 days after injury. 55 ONOO À itself causes significant neuronal loss and locomotor dysfunction when generated in the rat spinal cord in vivo. 56 The endogenous free radical scavenger, superoxide dismutase (SOD) can moderate this reaction.…”

Sildenafil Improves Epicenter Vascular Perfusion but not Hindlimb Functional Recovery after Contusive Spinal Cord Injury in Mice

“…Following spinal cord injury, NO levels exhibit a biphasic increase (Nakahara et al, 2002), with an immediate response within 30 min post-injury, and a second, delayed wave of increase, presumably due to inducible nitric oxide synthase (iNOS) activation and the post-traumatic inflammatory response (Conti et al, 2007). Although sildenafil treatment decreases microglial activation/macrophage infiltration in a murine model of multiple sclerosis (Pifarre et al, 2011), sildenafil treatment had no effect on microglial/macrophage staining following contusive SCI.…”