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Abstract

Background and Objectives: Compression spinal cord injury is a highly heterogeneous lesion, and tools to delineate pathophysiological recovery needed. Our objective was to profile the protective or reversal effects of RKI-1447 on neuron regeneration and its correlation with the degree of tissue damage in the rats with induced compression injury at the T7 level. Methodology: Albino rats of Sprague Dawley strain, 08 weeks of age, weighing 250 +10gm (n= 64) were used in this study. The animals were procured from the Animal House of Khyber Medical University, IBMS campus. Every experiment was carried out following a protocol that the Institutional Animal Ethics Committee authorized in 09.09.2020 under the (DIR / (KMU AS & RB/BD/001187) under the 89th meeting. The study duration was for 03 years, in which the histological studies took 06 months. Two groups of animals were formed. The experimental group and the control group (A). The experimental groups were further divided into four subgroups i.e. B, C and D. Group A was a sham group, in which rats were incised at level T7 only. Spinal cord compression injury at T7 level was performed in groups B, C and D. Group B was treated only with placebo while the group C and D, were treated with RKI-1447, with a dose of 0.3 and 0.6 µg/kg/b.w. respectively. For histological analysis, the animals were sacrificed 7, 14 and 28 days after the completion of behavioral studies. The staining pattern of glial fibrillary acidic protein (GFAP) for Astrocytosis/Reactive astrocytes, GAP-43, for Axonal growth/sprouting and Neu N for neuronal number for viability of neurons were observed. Results: All the group animals were evaluated daily after surgery. Consequently, our research showed that rats in group A healed quickly with just the Laminectomy procedure. In experimental rats, both groups C and D showed improved behavioral and histological results. In contrast, group B demonstrated sluggish and inadequate recovery. Additionally, group D rats showed superior performance in behavioral assessments, and their histological scores significantly surpassed those of group C. Group "D" excelled over group "C," probably because of the high dosage of RKI-1447 (0.6 µg/kg) administered to group D. Regarding the time-related effects of RKI-1447, the 28-day survival treatment yielded promising outcomes compared to the 14-days treatment. Conclusion: The current research presents evidence suggesting that both functional and morphological outcomes following spinal cord compression injury can progress in a discontinuous, non-linear fashion, despite the injury levels being graded in a linear manner. Serum levels of GFAP, GAP-43 and NeuN, may serve as potential biomarkers for assessing the severity of traumatic conditions and traumatic limb injuries. However, further animal studies are necessary to translate these findings into clinical applications.