Abstract
Spinal cord injury (SCI) is a serious condition that results in disability and has a high morbidity rate; its treatment is very difficult. Although troxerutin and cerebroprotein hydrolysate (TCH) injections have been extensively used in clinics in China for the treatment of traumatic brain injury (TBI) and cerebral stroke, the potential efficacy of TCH injection in the treatment of SCI has never been revealed. In this study, the effects of administering TCH injections on neurological recovery in post-SCI rats were first tested with regard to the behavior and histology; subsequently, the specific expression profile of mRNAs and long noncoding RNAs (LncRNAs) in their spinal cords were conducted using RNA sequencing (RNA-seq). The LncRNA-mRNA networks were also elucidated. After SCI, we found that TCH injection with the right dose is effective for the recovery of locomotion function and repairing of the damaged tissue in the spinal cord; TCH injection is also discovered to have a role in the regulation of 443 differentially expressed genes (DEGs) and 27 differentially expressed LncRNAs (DELs) that are identified to have multiple functions, including locomotion, blood vessel morphogenesis, thiamine metabolism, Hippo signaling pathway, and axon guidance, by applying the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis. In addition, it is revealed that, after SCI, the highly expressed LncRNA AABR07071383.1 in the post-SCI cis/trans-regulates the expression of mRNA Acpp mRNA that encodes a key enzyme involved in the metabolic process of thiamine in the abirritation of the dorsal root ganglion (DRG), which implies that TCH injection may be more effective when administered with benfotiamine (a common treatment drug).
Highlights
Spinal cord injury (SCI) mostly occurs due to a traumatic event that causes severe damage to the central nervous system (CNS)
Raw data obtained from Illumina sequencing were primarily transformed into FASTQ format, in which the base and its mass fraction of reads could be recorded. e results of each sample are shown in Table 1; it was observed that the error rate of the base was below the upper limit for subsequent analyses, the content of GC-content percentage was normal, and the data size was permissible for long noncoding RNAs (LncRNAs) recognition and analysis. e quality of reads was assessed by base mass distribution analysis and represented by quality value (Q) as shown in Figure S1; Q declined as the process of sequencing progressed since the enzyme activity and sensitivity of the reactants reduced; all our samples were qualified for subsequent analyses
Troxerutin is a derivative of bioflavonoid rutin that is widely distributed in fruits, vegetables, and grains [17]. ere is mounting clinical evidence to show that troxerutin possesses pharmacological effects in the treatment of multiple diseases
Summary
Spinal cord injury (SCI) mostly occurs due to a traumatic event that causes severe damage to the central nervous system (CNS). It results in various degrees of motor and sensory dysfunction [1, 2], high mortality, and multiple complications such as neuropathic pain, syringomyelia, and spasticity, thereby inflicting suffering to more than 40 thousand people worldwide each year [3, 4]. It has been known to regulate the metabolism and development functions of neurons to protect against acute ischemic stroke and traumatic brain injury (TBI) [10, 11]. Troxerutin and cerebroprotein hydrolysate (TCH) injection contains 40 mg/ml troxerutin and cerebroprotein hydrolysate with a total nitrogen content of 0.5 mg/ml has been approved and is widely used in the clinical treatment of TBI
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