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1.
Background: Spinal cord has a limited capacity to repair; therefore, medical interventions are necessary for treatment of injuries. Transplantation of Schwann cells has shown a great promising result for spinal cord injury (SCI). However, harvesting Schwann cell has been limited due to donor morbidity and limited expansion capacity. Furthermore, accessible sources such as bone marrow stem cells have drawn attentions to themselves. Therefore, this study was designed to evaluate the effect of bone marrow-derived Schwann cell on functional recovery in adult rats after injury. Methods: Mesenchymal stem cells were cultured from adult rats’ bone marrow and induced into Schwann cells in vitro. Differentiation was confirmed by immunocytochemistry and RT-PCR. Next, Schwann cells were seeded into collagen scaffolds and engrafted in 3 mm lateral hemisection defects. For 8 weeks, motor and sensory improvements were assessed by open field locomotor scale, narrow beam, and tail flick tests. Afterwards, lesioned spinal cord was evaluated by conventional histology and immunohistochemistry. Results: In vitro observations showed that differentiated cells had Schwann cell morphology and markers. In this study, we had four groups (n = 10 each): laminectomy, control, scaffold and scaffold + Schwann cells. Locomotor and sensory scores of cell grafted group were significantly better than control and scaffold groups. In histology, axonal regeneration and remyelination were better than control and scaffold groups. Conclusion: This study demonstrates that bone marrow-derived Schwann cells can be considered as a cell source for Schwann cells in SCI treatment. Key Words: Rats, Spinal cord injuries (SCI), Bone marrow, Schwann cells, Cell transdifferentiation  相似文献   

2.
Background: The present study investigated the functional maturity of oligodendrocyte derived from rat bone marrow stromal cells (BMSC). Methods: The BMSC were isolated from female Sprague-Dawley rats and evaluated for different markers, such as fibronectin, CD106, CD90, Oct-4 and CD45. Transdifferentiation of OLC from BMSC was obtained by exposing the BMSC to DMSO and 1 µM all-trans-retinoic acid during the pre-induction stage and then induced by heregulin (HRG), platelet-derived growth factor AA (PDGFR-α), fibroblast growth factor and T3. The neuroprogenitor cells (NPC) were evaluated for nestin, neurofilament 68, neurofilament 160 and glial fibrillary acidic protein gene expression using immunocytochemistry. The OLC were assessed by immunocytochemistry for O4, oligo2, O1 and MBP marker and gene expression of PDGFR-α was examined by RT-PCR. Results: Our results showed that the fibronectin, CD106, CD90, CD45 and Oct-4 were expressed after the fourth passage. Also, the yield of OLC differentiation was about 71% when using the O1, O4 and oligo2 markers. Likewise, the expression of PDGFR-α in pre-oligodendrocytes was noticed, while MBP expression was detected in oligodendrocyte after 6 days of the induction. Conclusion: The conclusion of the study showed that BMSC can be induced to transdifferentiate into mature OLC. Key Words: Bone marrow stromal cell, Triiodothyronine, Platelet-derived growth factor α  相似文献   

3.
Background: Neutrophil infiltration plays an important role in inflammatory reactions following spinal cord injury (SCI) and these cells cause substantial secondary tissue damage. The purpose of this study was to determine the effect of oleuropein (OE) on myeloperoxidase (MPO) activity as an index of neutrophil infiltration. Methods: Rats were randomly divided into four groups of 7 rats each as follows: sham-operated group, trauma group, and OE treatment groups (20 mg/kg, i.p., immediately and 1 hour after SCI). Spinal cord samples were taken 24 hours after injury and studied for determination of MPO activity. Results: The results showed that MPO activity was significantly decreased in OE-treated rats. Conclusion: On the basis of our findings, we propose that OE may be effective in protecting rat spinal cord from secondary damage by modulating of neutrophil infiltration.Key Words: Oleuropein (OE), Neutrophil infiltration, Myeloperoxidase  相似文献   

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5.
Background: The present study was designed to evaluate the secondary microglial activation processes after spinal cord injury (SCI). Methods: A quantitative histological study was performed to determine ED-1 positive cells, glial cell density, and cavitation size in untreated SCI rats at days 1, 2, and 4, and weeks 1, 2, 3, and 4. Results: The results of glial cell quantification along the 4900-µm long injured spinal cord showed a significant increase in glial cell density percentage at day 2 as compared to other days. Whereas the highest increase in ED-1 immunoreactive cells (monocyte/phagocyte marker in rats) was observed at day 2 (23.15%) post-injury. Evaluation of cavity percentage showed a significant difference between weeks 3 and 4 post-injury groups. Conclusions: This study provides a new insight into the multiphase immune response to SCI, including cellular inflammation, macrophages/microglia activation, glial cell density, and cavitation. Better understanding of the inflammatory processes associated with acute SCI would permit the development of better therapeutic strategies. Key Words: Spinal cord injuries, Inflammation, Microglia, Macrophages  相似文献   

6.
Background: The primary phase of traumatic spinal cord injury (SCI) starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. Valproic acid (VPA) is a histone deacetylase inhibitor. Acetylation of histones is critical to cellular inflammatory and repair processes. Methods: In this study, rats were randomly assigned to five experimental groups (laminectomy, untreated, and three VPA-treated groups). For SCI, severe contusion was used. In treated groups, VPA was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. To compare locomotor improvement among experimental groups, behavioral assessments were performed by the Basso, Beattie and Bresnahan (BBB) rating scale. The expression of neurotrophins was evaluated by RT-PCR and real-time PCR. Results: VPA administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mRNA levels. Local inflammation and the expression of the lysosomal marker ED1 by activated macrophages/microglial cells were reduced by VPA and immunoreactivity of acetylated histone and microtubule-associated protein were increased. Conclusion: The results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test (BBB scale) with rapid recovery.Key Words: Inflammation, Epigenetics, Valproic acid (VPA)  相似文献   

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8.
Background: P2X4 receptor (P2X4R), a purinoceptor expressed in activated spinal microglia, plays a key role in the pathogenesis of neuropathic pain. Spinal nerve injury induces up-regulation of P2X4R on activated microglia in the spinal cord, and blockade of this receptor can reduce neuropathic pain. The present study was undertaken to determine whether paroxetine, an inhibitor of P2X4R, could attenuate allodynia and hyperalgesia in chronic constriction injury (CCI) model of neuropathic pain when used preemptively or after the sciatic nerve injury. Methods: Male Wistar rats (150-200 g, n = 6) were divided into 3 different groups: 1- CCI vehicle-treated group, 2- Sham group, and 3- CCI paroxetine-treated group. Paroxetine (10 mg/kg, i.p.) was administered 1 h before surgery and continued daily until day 14. In other part of the study, paroxetine (10 mg/kg, i.p.) was administered at day 7 post injury and continued daily until day 14. von Frey filaments for mechanical allodynia and analgesia meter for thermal hyperalgesia were used to assay pain behavior. Results: In a preventive paradigm, paroxetine significantly attenuated both mechanical allodynia and thermal hyperalgesia (P<0.001). A significant decrease in pain behavior was seen with paroxetine on existing allodynia (P<0.001) and hyperalgesia (P<0.01) when initiated at day 7 post injury. Conclusion: It seems that paroxetine can attenuate pain behavior when administered before and also after sciatic nerve injury in CCI model of neuropathic pain. Key Words: Paroxetine, P2X4 receptor (P2X4R), Allodynia, Hyperalgesia  相似文献   

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10.
Background: Brain hypoxia-ischemia is a human neonatal injury that is considered a candidate for stem cell therapy. Methods: The possible therapeutic potential of human umbilical cord blood (HUCB) stem cells was evaluated in 14-day-old rats subjected to the right common carotid occlusion, a model of neonatal brain hypoxia-ischemia. Seven days after hypoxia-ischemia, rats received either saline solution or 4 × 105 HUCB cells i.v. Rats in control group did not receive any injection. After two weeks, rats were assessed using two motor tests. Subsequently, rats were scarified for histological and immunohistochemical analyses. Results: Our immunohistochemical findings demonstrated selective migration of the injected HUCB cells to the ischemic area as well as reduction in infarct volume. Seven days after surgery, we found significant recovery in the behavioral performance in the test group (12.7 +/- 0.3) compared to the sham group (10.0 +/-0.05), a trend which continued to day 14 (15.3 ± 0.3 vs. 11.9 ± 0.5, P<0.05). Postural and motor asymmetries at days 7 and 14 in the test group showed a significant decrease in the percentage of right turns in comparison to the sham group (75% and 59% vs. 97% and 96%, P<0.05). Conclusion: The results show the potential of HUCB stem cells in reduction of neurologic deficits associated with neonatal hypoxia-ischemia. Key Words: Hypoxia-Ischemia, Nerve cell, Umbilical Cord Blood  相似文献   

11.
Background:The polysialylated neural cell adhesion molecule (PSA-NCAM) is expressed in developing brain. Fetal brain damage is caused by different conditions such as seizure and hypoxia. The present study was designed to investigate the effect of maternal seizures on the number of PSA-NCAM positive cells in pup''s hippocampus. Methods: Female Wistar rats were divided into four groups: (a) kindled rats which received PTZ (40 mg/kg, i.p.) during pregnancy from embryonic day 14-19 (E14-E19) every 48 h, (b) kindled rats which did not receive PTZ during pregnancy, (c) non-kindle, pregnant rats which received PTZ injection (40 mg/kg, i.p.) during pregnancy from E14 to E19 every 48 h, and (d) non-kindle, pregnant rats which received injection with an equal volume of normal saline as sham controls. At postnatal day 14 (PD14), rat pups were perfused, and their brain were fixed, embedded and coronal sections stained by immunohistochemistry method. The number of PSA-NCAM positive cells per unit area in the pup''s hippocampus was counted. Results: The number of PSA-NCAM positive cells in the CA1, CA3, and DG fields of pup''s hippocampus, which was obtained from mothers who experienced PTZ injection during pregnancy, was decreased approximately 2.6 (P = 0.001), 2 (P = 0.001), and 2.1 (P = 0.001) times compared with non-PTZ treated maternal groups, respectively. Conclusions: Our study showed that maternal seizures reduced the number of neurons and also PSA-NCAM positive cells per unit area in the offspring hippocampus that it may cause impairment in hippocampal functions.Key Words: Epilepsy, Polysialylated neural cell adhesion molecule (PSA-NCAM), Hippocampus, Seizures  相似文献   

12.
The influence of flaxseed (Linum usitatissimum L.) and its total non-digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM)-induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50?±?3.5) compared with the AOM treatment (34.00?±?11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl-2, bax and caspase-3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21-independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF + AOM group exhibited the expression of caspase-3, decreased bcl-2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed.  相似文献   

13.
Nitrogen fertilization is one of the factors that influences Bemisia tabaci (Gennadius) population density. The aim of this study was to determine the effects of three N application rates (75, 205 and 335 mg/l) and three ratios of NO3:NH4+ ions (92:8, 75:25 and 55:45) in standard nutrient solution (205 mg/l N) on the population density of B. tabaci. The experiments were conducted on spring-summer hydroponic crops of tomato. The effect of plant stratum on the whitefly population was also determined. The aggregation of B. tabaci adults as well as their oviposition rate was higher at 205 and 335 mg/l N than on plants grown at 75 mg/l N. By the end of the experiment (60 d after infestation), the number of nymphs on plants at 205 mg/l N was higher than on plants at 75 mg/l N. The number of pupae was lowest on plants supplied with 75 mg/l N. An increase in NH4+ percentage in standard nutrient solution (from 25% to 45% of the total N) reduced adult population density and oviposition rate. The density of nymphs and pupae, at 60 d after infestation, was lower on the tomato plants grown at 75:25 and 55:45 NO3:NH4+ ratios compared to the 92:8 ratio. The 75:25 and 55:45 NO3:NH4+ ratios resulted in a higher incidence of blossom-end rot of tomato fruit, with a lower incidence of disorder at 75:25 than at the 55:45 ratio. Plant stratum influenced adult whitefly distribution in two years of the study. Middle stratum leaves were more attractive to adults in both years. The results demonstrate the effects of N fertilization (N rate and the ratio of NO3:NH4+) and plant stratum on B. tabaci population density.  相似文献   

14.
Background: The leaves of Eucalyptus globulus (eucalyptus) are used for treatment of diabetes mellitus in traditional medicine. The aim of this study was to evaluate the effects of eucalyptus in treatment of established systemic infection with Candida albicans in normal and streptozotocin-induced diabetic rats. Methods: Sixty normoglycemic male Wistar rats, weighing 200-250 g, were selected and randomly divided into six groups (n= 10): normal control, control + C. albicans, control + eucalyptus + C. albicans, diabetic control, diabetic + C. albicans, diabetic + eucalyptus + C. albicans. Diabetes was induced after a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and eucalyptus was added to the diet (62.5 g/kg) and drinking water (2.5 g/L) of treated animals for 4 weeks. The concerned groups were inoculated with C. albicans 15 days after diabetes induction. At the end of one month experiment, fasted rats were killed by cervical decapitation. Blood was collected from neck vein for estimation of glucose. C. albicans concentrations were estimated in liver and kidneys using serial dilution culture of tissue homogenates. Results: Eucalyptus administration significantly improved the hyperglycemia, polydipsia, polyphagia, and it also compensated weight loss of diabetic rats (P<0.05). Moreover, eucalyptus caused a significant reduction in C. albicans concentration in liver and kidney homogenates (P<0.01). Conclusion: The results revealed that eucalyptus improves Candidia infection in normal and diabetic rats that in some ways validates the traditional use of this plant in treatment of diabetic patients. Key Words: Diabetes mellitus, Eucalyptus globulus, Candida albicans  相似文献   

15.
A backcross inbred line population derived from a cross between Koshihikari and Kasalath was used to dissect the genetic relationship among chalkiness, protein content, and paste viscosity properties in rice in three environments. A total of 11 traits (or parameters) were analyzed, including percentage of grains with chalkiness (PGWC), protein content (PC) and protein index (PI), and eight parameters from the viscosity profile. PGWC, PC and PI were significantly correlated with the paste viscosity parameters. We identified 39 QTLs in three environments; ten QTL clusters emerged. Eight QTLs were consistently detected across the three environments and further confirmed using a set of chromosome segment substitution lines (CSSLs) where Kasalath was used as the donor parent and Koshihikari as the recurrent parent. One and two major clusters on chromosome 6 corresponded to the Wx and Alk loci, respectively. The former was responsible for PGWC and most of the viscosity parameters, and the latter for PI and some viscosity parameters. Particularly, QTL qPI-6.1 was linked with both the Wx and Alk loci. The co-locations of QTLs for PGWC and viscosity parameters and the linkage of qPI-6.1 and qBDV-6 at the Wx locus could be largely responsible for the phenotypic correlations between these traits.  相似文献   

16.
Background:IM, a strong and selective TKI, has been approved as the front line of treatment in CML patients. In spite of satisfactory results of imatinib in the treatment of patients with CML, patients with treatment failure or suboptimal response developed resistance that might be because of pharmacogenetic variants. This study attempted to evaluate the influence of ABCB1 gene polymorphisms and smoking on CML risk and resistance to imatinib. Methods: ABCB1 (c.1236C>T, c.3435C>T) polymorphisms were genotyped in 98 CML patients and 100 sex- and age-matched healthy subjects by PCR-RFLP method, followed by sequencing. The patients were evaluated for cytogenetic response by the standard chromosome banding analysis in regular intervals. Results:Our results showed that c.1236CC genotype was significantly associated with imatinib resistance (OR = 3.94; p = 0.038). Analysis of the joint of SNP-smoking combination showed that smokers with c.1236TT/CT and c.1236CC genotypes had the increased risk of CML (OR = 6.04; p = 0.00 and OR = 4.95, p = 0.005) and treatment failure (OR = 5.36, p = 0.001 and OR = 15.7, p = 0.002), respectively. Smokers with c.3435TT/CT and c.3435CC genotypes also displayed the elevated risk of CML development (OR = 6.01, p = 0 and OR = 4.36, p = 0.011) and IM resistance (OR = 5.61, p = 0.001 and OR = 13.58, p = 0.002), respectively. Conclusion:Our findings suggest that c.1236CC genotype has clinical importance in the prediction of treatment outcome with IM, and smoking could have a synergistic role in CML risk and IM resistance. Key Words: ATP binding cassette transporter subfamily B, Imatinib mesylate, Smoking  相似文献   

17.
Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group—vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.  相似文献   

18.
To evaluate neurological changes developing during paediatric Acute Lymphoblastic Leukaemia (ALL) therapy clinically and through electrophysiological Study of Somatosensory Evoked Potentials (SSEPs) changes in different phases of therapy. Thirty five-ALL patients with age range from 3-14 years were included compared to 30 healthy controls. History, neurological examination, complete blood counts, cytological examination of bone marrow aspirate and cerebrospinal fluid with Measurement of Serum Methotrexate (MTX) were done. The SSEPs were performed and patients subjected to another SSEP with measurement of serum MTX level before and 10 days after intra-thecal injection (IMTX). Clinical neurological findings in patients after induction were depressed deep tendon reflexes (43.3%), hypotonia (28.6%), lost pain sensation (28.6%), muscle weakness (17.1%) and movement disorders (17.1%). Percentage of delayed SSEPs after induction were at levels of brachial plexus (28.6%), spinal cord (68.6%), cortical conduction (31.4%), ERB-N13 Inter Peak Latency (IPL) (74.3%) and N13-N20 IPL (17.1%) in the studied patients. Significant prolonged latency of N13 (p = 0.005), N20 (p = 0.04) and IPL of ERB-N 13 (p = 0.005), N13-N20 (p = 0.01), Inter-Side Difference (ISD) of N13 (p = 0.01), ERB-N13 (p = 0.02) and N13-N20 (p = 0.03) after induction compared to values at diagnosis. Significant positive correlation were found between serum MTX after IMTX with N13-N20 IPL (p = 0.01), N20 ISD (p = 0.03) with significant prolongation in N20 latency, N13-N20 IPL and ISD of N20 compared to values before injection. ALL patients have prolonged latency of SSEPs at cervical cord and cortical levels which increased after IMTX due to axonal injury throughout the cord. SSEPs could be an early diagnostic tool for subclinical neuropathy.  相似文献   

19.
Bone-related complications are among the highest concerning metabolic diseases in the modern world. Bone fragility and susceptibility to fracture increase with age and diseases like osteoporosis. Elevated adipogenesis in bone results in osteoporosis and loss of bone mass when coupled with lack of osteoblastogenesis. In this study the potential effect of Salicornia herbacea extract against osteoporotic conditions was evaluated. Adipogenesis inhibitory effect of S. herbacea has been evidenced by decreased lipid accumulation of differentiating cells and expression levels of crucial adipogenesis markers in 3T3-L1 pre-adipocytes. S. herbacea treatment reduced the lipid accumulation by 25% of the control. In addition, mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α and sterol regulatory element binding protein (SREBP)1c were inhibited by the presence of S. herbacea. Bone formation enhancement effect of S. herbacea was also confirmed in MC3T3-E1 pre-osteoblasts. The presence of S. herbacea significantly elevated the alkaline phosphatase (ALP) activity by 120% at a concentration of 100 μg/mL in differentiating osteoblasts. S. herbacea also significantly increased the expression of osteoblastogenesis indicators, ALP, bone morphogenetic protein (BMP)-2, osteocalcin and collagen type I (collagen-I). In conclusion, S. herbacea possess potential to be utilized as a source of anti-osteoporotic agent that can inhibit adipogenesis while promoting osteoblastogenesis.  相似文献   

20.

Background:

Oral vanadyl sulfate (vanadium) induces normoglycemia, proliferates beta cells and prevents pancreatic islet atrophy in streptozotocin-induced diabetic rats. Soteriological method is used to quantitate the proliferative effects of vanadium on beta-cell numbers and islet volumes of normal and diabetic rats.

Methods:

Adult male Sprague-Dawley rats were made diabetic with intravenous streptozotocin injection (40 mg/kg). Normal and diabetic rats were divided into four groups. While control normal and diabetic (CD) groups used water, vanadium-treated normal (VTN) and diabetic (VTD) groups used solutions containing vanadyl sulfate (0.5-1 mg/mL, VOSO4+5H2O). Tail blood samples were used to measure blood glucose (BG) and plasma insulin. Two months after treatment, rats were sacrificed, pancreata prepared, and stereology method was used to quantitatively evaluate total beta cell numbers (TBCN) and total islet volumes (TISVOL).

Results:

Normoglycemia persisted in VTN with significantly decreased plasma insulin (0.190.08 vs. 0.970.27 ng/dL, P<0.002). The respective high BG (53249 vs. 14446 mg/dL, P<0.0001) and reduced plasma insulin (0.260.15 vs. 0.540.19 ng/dL, P<0.002) seen in CD were reversed in VTD during vanadium treatment or withdrawal. While the induction of diabetes, compared to their control, significantly decreased TISVOL (1.90.2 vs. 3.030.6 mm3, P<0.003) and TBCN (0.990.1 vs. 3.20.2 x 106, P<0.003), vanadium treatment significantly increased TISVOL (2.90.8 and 4.071.0 mm3, P<0.003) and TBCN (1.50.3 and 3.80.6 x 106, P<0.03).

Conclusion:

Two-month oral vanadium therapy in STZ-diabetic rats ameliorated hyperglycemia by partially restoring plasma insulin. This action was through proliferative actions of vanadium in preventing islet atrophy by increasing beta-cell numbers.Key Words: Vanadium, Pancreas, Islet volumes, Rats  相似文献   

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