A.SINGH, J. LACSINA, T.HANNANIA
Spinal cord injury (SCI) is a two-phase process, encompassing both primary and secondary injuries. While the term “primary injury” refers to structural damage caused by a mechanical trauma, the term “secondary injury” is used to describe a complex interaction of patho physiological and biochemical mechanisms initiated by the primary injury (Sekhon and Fehlings, 2001). One of the key processes involved in secondary damage is iNOS (Nitric oxide synthase)-mediated cell damage, through the generation of reactive nitrogen species peroxinitrates. Peroxynitrates results in lipid peroxidation of membranes and cause disturbances in tissue homeostasis that is severe enough to cause cellular damage and eventually cell death (Beattie et al., 2000). Hence, suppression of peroxynitrate formation should decrease lipid peroxidation thereby decreasing damage created by secondary injury within the context of CNS injury. One way to decrease the peroxynitrate formation in the injured spinal cord includes inhibition of iNOS with selective and non-selective antagonists such as Aminoguanidine, and Curcumin, respectively.
Here we investigated the possible neuroprotective effects of these iNOS inhibitors in an established animal model contusive (SCI), and whether they can contribute to functional recovery.. Female Sprague Dawley rats were injured and subjected to following behavioral tests: Basso Beattie and Bresnahan (BBB),foot print analysis and grid walk error test. Compared to vehicle-treated controls, rats treated with aminoguanidine (150 mg/kg; i.p) displayed a significantly faster recovery of function in the open-field test during the first 4 weeks of the 6-week study. On the other hand curcumin administered rats displayed a slow recovery of function, and were only significant at the end of the study i.e 4 weeks after injury. At the endpoint of the experiment (6 weeks after injury), foot print analysis revealed a significantly improved stride length and foot placement in aminoguanidine treated groups only. In grid walk error test there was a decrease in the foot fall errors with the administration of both compounds. Together, these results suggest an early significant neuroprotective effect of aminoguanidine versus late effects in functional recovery with curcumin after SCI in rats. Aminoguanidine revealed better effects in terms of walking stability, body support as compared to Curcumin treated rats.