Protective and Therapeutic Effects of Bovine Amniotic Fluids Collected in Different Trimesters on the Epidural Fibrosis After Experimental Laminectomy in Rats.

BACKGROUND: The aim of this study was to investigate the protective and therapeutic effects of bovine amniotic fluid (BAF) on the inhibition of epidural fibrosis (EF) after experimental laminectomy. METHODS: Forty female Sprague Dawley rats were used. The amniotic fluids were collected from each trimester of a pregnant cow. The rats were divided into 5 groups. Whereas no laminectomy was applied to the control group, animals in the sham group underwent laminectomy. Laminectomy was performed in the animals in other groups and the operation area was closed by dripping 1 mL of BAF collected in 3 trimesters of pregnancy. Animals were killed 28 days after the operation. RESULTS: Compared with control, VEGF gene expression levels were downregulated approximately 5-fold in BAF-2. Whereas IL-6 was upregulated approximately 8-fold in the sham, it was downregulated 5-fold and 3-fold in BAF-1 and BAF-2, respectively. There was downregulation in BAF-2 and BAF-3 in terms of CD105 gene expression levels. TGFß1 was upregulated approximately 2-fold in the sham group and downregulated in BAF-1 and BAF-2. Although histopathologic alterations including EF grade and fibroblast cell density were found to increase in the sham group, all BAF treatment decreased those of alterations. The highest CD105 immunoreactivity was detected in the sham group. All BAF treatment markedly aggravated fibrosis via decreasing CD105 immunoreactivity. In terms of grading parameters, almost the closest grades to the control were determined in the BAF-2. BAF collected in the second trimester is most effective in healing of scar tissue and preventing fibrosis via decreasing microvessel and fibroblast densities. CONCLUSIONS: The results indicate that BAF may be used as a potential protective agent to prevent EF.

The Matrix Metalloproteinase Inhibitor Batimastat Reduces Epidural Fibrosis After Laminectomy in Rats.

AIM: To investigate the efficacy of locally applied batimastat after laminectomy in preventing postoperative epidural fibrosis. MATERIAL AND METHODS: Thirty-two Wistar albino male rats weighing 200?250 g were used. The rats were assigned to four different groups (I-Control group, II-sham group, III-Laminectomy+Batimastat group, and IV-Laminectomy+SpongostanTM group). The rats were euthanized 28 days after surgery before TNF-?, IL6, IL-1?, IL10, TGF-?1, and MMP9 gene expression levels of tissue in the surgical area were determined with qPCR. TNF-?, IL6, and IL10 protein levels were also measured in both tissue and plasma. In addition, the surgical area was evaluated by histopathological and immunohistochemical methods. RESULTS: TNF-?, IL6, and IL-1? gene expression levels were higher in the batimastat group than in the control group. Whereas IL10 gene expression levels increased about two-fold in the sham and SpongostanTM groups, in the batimastat group, it was similar to that in the control group. TGF-?1 gene expression was three-fold higher in the sham group but was similar to that in the control group in both batimastat and SpongostanTM groups. MMP9 gene expression levels significantly decreased only in the batimastat group. In addition, fibrosis score, fibroblast cell count, inflammatory cell count, and CD105 expression decreased in the batimastat group relative to the control. CONCLUSION: Molecular and pathological examination results suggested that batimastat is an effective agent in reducing the occurrence of epidural fibrosis after laminectomy.

Ebselen, an Active Seleno-Organic Compound, Alleviates Articular Cartilage Degeneration in a Rat Model of Knee Osteoarthritis.

Osteoarthritis (OA) is a prevalent articular disease mainly characterized by extracellular matrix degradation, apoptosis, and inflammation, which lead to cartilage destruction and abnormal bone metabolism. With undesirable side effects, current limited symptomatic treatments are aimed at relieving pain and improving joint mobility in patients with OA. Intra-articular (IA) hyaluronic acid (HA) injection, as a nonsurgical therapy, is commonly used in the clinical management of knee OA, but the efficacy of this therapeutic option remains controversial. Ebselen has tremendous pharmacological importance for some diseases due to its antioxidant, antiapoptotic, and anti-inflammatory features. However, there is no research examining the therapeutic effect of Ebselen in OA using the rat OA model. Therefore, we aimed to investigate the therapeutic effect of Ebselen on cartilage degeneration and its role in bone morphogenetic protein 2 (BMP2) and nuclear factor kappa B (NF-κB) signaling in the molecular pathogenesis of OA. We induced a knee OA model in rats with an IA injection of monosodium-iodoacetate (MIA). After the treatment of Ebselen, we evaluated its chondroprotective effects by morphological, histopathological, and immunohistochemical methods and an enzyme-linked immunosorbent assay. We report for the first time that Ebselen treatment alleviated articular cartilage degeneration in the rat knee OA model and reduced MIA-induced BMP2 and NF-κB expressions. In addition, our results unveiled that Ebselen decreased IL-ß and IL-6 levels but did not affect COMP levels in the rat serum. Ebselen could be a promising therapeutic drug for the prevention and treatment of OA by alleviating cartilage degeneration and regulating BMP2 and NF-κB expressions.

Investigation of Neuroprotective and Therapeutic Effects of Hesperidin in Experimental Spinal Cord Injury.

AIM: To investigate the neuroprotective and therapeutic efficacy of hesperidin against secondary damage following traumatic spinal cord injury. MATERIAL AND METHODS: A total of 32 male Wistar albino rats weighing 250?300 g were randomly divided into four groups (n=4): group I, control group; group II, sham group; group III, preconditioning group, and group IV, treatment group. A rat model of spinal cord injury was established by dropping a weight of 100 g/cm on the spinal cord exposed at T7?T10 with dorsal laminectomy. In neurological examination after the trial period, inclined planed test, modified Tarlov scale, and finger extension test were performed. Furthermore, the bioefficacy of hesperidin was investigated histopathologically, biochemically, and immunohistochemically using blood and tissue samples obtained from the experimental animals. RESULTS: Neurological examination following spinal cord injury revealed that hesperidin significantly contributed to improvement in the 24-hour period. Biochemical analyses revealed that hesperidin showed anti-inflammatory effects by decreasing IL-1? and TNF-? levels at the 24th hour as well as strong antioxidant activity by increasing TAS levels in groups III and IV. Histopathologically, hesperidin reduced hemorrhage, laceration, axonal and neuronal degeneration, necrosis, inflammatory reaction, and edema in groups III and IV. Immunohistochemically, hesperidin reduced the number of caspase 3-positive apoptotic cells in groups III and IV. CONCLUSION: Hesperidin showed antioxidant, anti-inflammatory, and anti-apoptotic effects during the acute period following spinal cord injury; thus, hesperidin shows neuroprotective and therapeutic efficacy in spinal cord injury.