Intravenous administration of human chorionic membrane mesenchymal stem cells promotes functional recovery in a rat traumatic brain injury model.

Human chorionic membrane mesenchymal stem cells (hCM-MSCs) have increasingly emerged as an excellent source of transplanted cells for regenerative therapy as they can be isolated via a non-invasive and simple method with high proliferative capabilities. However, the roles and mechanisms of hCM-MSCs on traumatic brain injury (TBI) animal models have not been investigated yet. The aim of this study was to investigate the therapeutic potential and mechanism of hCM-MSCs transplantation in a rat model of TBI. Adult male Sprague-Dawley rats were subjected to moderate lateral fluid percussion-induced TBI. At 2 h after TBI, hCM-MSCs, or PBS were administered intravenously via the tail vein. Neurological function, brain water content, Evans blue dye extravasation, immunofluorescence staining, and enzyme-linked immunosorbent were evaluated. The results showed that transplanted hCM-MSCs were observed in the injured brain. Compared with the PBS group, hCM-MSCs treatment significantly decreased the numbers of M1 macrophages/microglia, MPO + neutrophils and caspase-3 + cells ( P  < 0.01). Meanwhile, hCM-MSCs treatment significantly reduced the expression levels of the pro-inflammatory cytokines (TNF-α, interleukin-(IL)6 and IL-1ß) while increasing the numbers of M2 macrophages/microglia and the expression of the anti-inflammatory cytokines IL-10 ( P  < 0.01). In addition, hCM-MSCs treatment significantly reduced brain water content and Evans blue extravasation. Lastly, hCM-MSCs treatment significantly promoted neurogenesis and angiogenesis, and attenuated neurological deficits. Collectively, these findings indicate that hCM-MSCs exhibited effective therapeutic efficacy in a rat TBI model, and its mechanism may be by reducing inflammation, apoptosis and the blood-brain barrier disruption, promoting angiogenesis and neurogenesis.

Association of the genetic polymorphisms in pre-microRNAs with risk of ischemic stroke in a Chinese population.

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29-3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10-1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00-1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20-2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09-1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.

[Effects of exendin-4 on rat cardiomyocyte apoptosis early after severe scald injury].

OBJECTIVE: To observe the effect of exendin-4 on cardiomyocyte apoptosis in the early stage after scald injury in rats and explore the mechanisms. METHODS: Fifty-four healthy adult SD rats were randomly divided into normal control group (n=6), scald group (n=24) and scald with exendin-4 treatment group (n=24). In the latter two groups, the rats were subjected to 30% TBSA full-thickness scald burns on the back, and Parkland formula was used for determining the resuscitation fluid volume. In exendin-4 treatment group, the rats received intraperitoneal injection of 5 µg/kg exendin-4 after the scald. Apoptosis of the cardiomyocytes from the left ventricle was determined by TUNEL assay and the activity of caspase-3 in the myocardium was assessed. RESULTS: In the scald group, the apoptotic index of the cardiomyocytes was increased at 6 h post-burn, reaching the peak level at 12 h, and maintained a significantly higher level than that in the normal control at 48 h (P<0.05). Myocardial caspase-3 activity in the scald group was increased at 6 h post-burn and reached the peak at 12 h, still maintaining a high levels at 24 h (P<0.05). In exendin-4 treatment group, the apoptotic index of the cardiomyocytes was significantly lower than that in the scald group at 6, 12, 24 and 48 h post-burn (P<0.05), and so was the caspase-3 activity at 6, 12 and 48 h (P<0.05). A significant positive correlation was found between the apoptotic index of the cardiomyocytes and myocardial caspase-3 activity in the rats (P<0.05). CONCLUSION: Exdendin-4 can inhibit rat cardiomyocyte apoptosis early after scald injury possibly by suppressing caspase-3 activity in the myocardium.

[Changes of aquaporin-1 expression in rat myocardium after severe burn].

OBJECTIVE: To investigate the changes in the myocardial expression of aquaporin-1 (AQP1) protein and its association with myocardial edema in rats with severe burns. METHODS: Forty-eight healthy adult Wistar rats were randomly divided into normal control group (n=6) and burn injury group with third degree burn of 30% total body surface area, and the latter group was further divided into 2, 4, 8, 12, 24, 48 and 72 h groups. The changes of myocardial water content were investigated by dry-wet weight methods. Enzyme-linked immunosorbent assay was used to detect the changes in AQP1 expression at different time points after sever burns. RESULTS: The myocardial water content and AQP1 expression increased significantly 2 h after the burn injury, reaching the peak levels at 12 h and remaining higher than the normal level at 48 h. A significant positive correlation was found between myocardial water content and AQP1 expression in the rats (r=0.868, P<0.01). CONCLUSION: The severity of myocardial edema after severe burn is correlated to the expression level of AQPl protein, suggesting the important role of AQPl protein in pathological progression of myocardial edema.

[Effect of local treatment with cooling and spray film on early edema of superficial II degree scald burns in rats].

OBJECTIVE: To investigate the anti-inflammatory effect of early local treatment with cooling and spray film on scald burn injury in rats. METHOD: Seventy-five Wistar rats were randomly divided into 5 groups including the sham-scalded group, untreated scald group, cooling group, spray film group, and cooling plus spray film group with corresponding treatments. After gross observation of the wounds, the tissues at the wounds were sampled at different time points after the injury to determine the total water content (wet: dry weight ratio) and prostaglandin E(2) (PGE(2)) levels using radioimmunoassay (RIA). RESULTS: Treatment with cooling and spray film significantly alleviated the swelling and effusion of the scald burns. At each of the time points, the water content and PGE(2) levels in the cooling group, spray film group and cooling plus spray film group were all lower than those in untreated scald group (P<0.01), but all higher than those in the sham-scalded group (P<0.01). The water content and PGE(2) levels were the lowest in cooling plus spray film group, and a significant correlation was noted between the water content and PGE(2) levels in the untreated scald group, cooling group, spray film group and cooling plus spray film group (P<0.01). CONCLUSIONS: Local treatment with cooling and spray film can alleviate the edema of superficial II degree scald burns in rats probably by reducing the levels of the inflammatory cytokines in the local tissues.

[Anti-inflammatory activity and healing-promoting effects of topical application of emu oil on wound in scalded rats].

OBJECTIVE: To investigate the effects of topical application of emu oil on wound healing in scalded rats. METHODS: In 144 male Wistar rats with 10%; total body surface superficial II degree scald treated on a random basis with physiological saline, povidone iodine and emu oil, respectively, the changes of the wound were observed and the wound tissue and blood samples harvested at different times after injury for evaluation of histopathological changes, total tissue water content (measured by wet:dry weight ratios), and tumor necrosis factor (TNF)-alpha levels in the wound tissue and plasma by enzyme-linked immunosorbent assay (ELISA). The general condition of the wound healing was also observed. RESULTS: After application of emu oil, the swelling and effusion of the burn wound were alleviated and evidences of wound infection or adverse effects were not observed. Pathological examination showed that emu oil could alleviate topical inflammation, which was particularly obvious on days 1 and 3 after injury as compared with the other two groups. On day 3 after injury, water content and TNF-alpha level in the tissues was markedly decreased with the application of emu oil (P<0.05), with a significant correlation between their changes (P<0.001) and shortened wound healing time (P<0.05). Pathological examination showed that emu oil could promote epithelialization and differentiation of various epidermal layers. CONCLUSION: Emu oil has topical anti-inflammatory activity in rats with superficial II degree scald, possibly in association with decreased levels of the proinflammatory cytokines in the tissues and can promote wound healing by inhibiting local secondary inflammation.

[Effects of topical emu oil on wound healing in scalded rats].

OBJECTIVE: To observe the effect of topical emu oil on wound healing in scalded rats. METHODS: Thirty Wistar rats with second degree scald were randomized into emu oil group, povidone iodine group and liquid paraffin group. The times of twisting of the rat body, water content and effusion of the scald wound and the percentage of wound healing were observed. RESULTS: Compared with povidone iodine and liquid paraffin, emu oil reduced the times of body twisting of the scalded rats, the water content and effusion of the scald wound, and increased the percentage of wound healing. CONCLUSION: Emu oil can alleviate inflammation in the scald wound and promote wound healing in rats.