Iranian Journal of Basic Medical Sciences
Volume:21 Issue: 6, Jun 2018

To reach an evidence-based knowledge in the context of the temporal-spatial pattern of neuronal death and find appropriate time of intervention in order to preserve spared neurons and promote regeneration after traumatic spinal cord injury (TSCI).
The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched (24 October, 2015) with no temporal or linguistic restrictions. Hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies evaluating time-dependent neuronal death following acute mechanical trauma to the spinal cord were included. We separately evaluated the fate of various populations of neurons including propriospinal neurons, ventral motor neurons, Clarke’s column neurons, and supraspinal neurons.
We found 11,557 non-duplicated studies. Screening through the titles and abstracts led to 549 articles, 49 of which met the inclusion criteria. Both necrotic and apoptotic neuronal deaths occur after TSCI, though necrosis is the prominent mechanism. There are differences in the responses of intrinsic neurons of the spinal cord to the TSCI. Also, the extent of neuronal death in the supraspinal neurons depends on the anatomical location of their axons.
In order to develop new therapies, selection of the injury model and time of intervention has a crucial role in the efficacy of therapy. In addition, examining the safety and efficacy of an intervention by reliable methods not confounded by the injury-related changes would promote translation of therapies to the clinical application.

Considering the lack of information, the effects of mild endurance exercise plus blood flow restriction (BFR) on electrocardiographic parameters, hypertrophy index, and expression of angiotensin II receptors type 1 (AT1R) and type 2 (AT2R) and apelin receptor (APJ) were assessed in hearts of old male rats.
Animal were grouped as control (CTL), Sham (Sh), lower extremities blood flow restriction (BFR), exercise (Ex), Sham exercise (Sh Ex), and blood flow restriction exercise (BFR Ex).
Exercise plus BFR significantly decreased the corrected QT (QTc) interval (P
Mild endurance exercise plus BFR can alter the expression of angiotensin II and apelin receptors that leads to cardiac hypertrophy and improves the ventricular conductivity of aging rats.

Juvenile idiopathic arthritis (JIA) is one of the most common chronic rheumatic diseases in children. The complex nature of this immune-mediated disease owes itself to several predisposing genes and environmental factors affecting its pathogenesis. Conducted in Iran, this study was originally intended to investigate every possible association between HLA DRB1 alleles and a susceptibility to JIA.
In this case-control study, 45 patients with a definite diagnosis of JIA based on International League against Rheumatism (ILAR) criteria were compared against 46 healthy controls. DNA samples taken from both groups were analyzed using PCR-sequence specific primers (PCR-SSP) method. Data analysis including parametric and nonparametric test and multivariate analysis was undertaken using the SPSS 11.5 software. A P-value Mean ages in case group and healthy controls were 14.64±6.21 and 13.73±6.39, respectively with no significant difference between the two groups (P=0.515). Sex difference between JIA group and healthy controls was also not significant (P=0.068) .The frequency of HLA-DRB1*01 was found the most frequent HLA-RB1 in our patients (33.3%). No significant statistical correlation between various HLA-DRB1 alleles and clinical subtypes of the disease could be established from the data. HLA-DRB1*11 was shown to raise protection to JIA (P=0.035, OR=2.755, 95% CI=0.963-8.055) in northeastern Iran. In addition, we found that HLA-RB1*09 is nominally associated with an increased risk of JIA (P=0.56, OR=2, 05, 95% CI=0.18-23.63).
HLA-DRB1*11 was shown to raise protection to JIA in northeastern Iran. The disparity of findings in other ethnicities prompts further investigations with larger sample sizes.

The study was intended to investigate the combined influence of two neuroprotective agents pramipexole and n-acetylcysteine on global cerebral ischemic reperfusion injury (GCIRI) model in rats.
GCIRI was induced by bilateral common carotid artery ligation (BCCA) in rats. Animals were divided into six groups. Groups I, II, and III received saline intraperitoneally (IP) (5 ml/kg/day, 0.9 % saline). The remaining groups IV, V, and VI were treated with n-acetylcysteine (NAC-150 mg/kg/day, IP), pramipexole (PPX-0.23 mg/kg/day, IP) alone and in combination, respectively. BCCA was done in all groups except in groups I (control) and II (sham control) of animals. The treatment was given for one week before the surgery and continued for two days after surgery. Subsequently, behavioral performances, biochemical estimations, proinflammatory cytokines, and histopathological evaluations were done.
NAC, PPX, and combination treatment groups showed significant ameliorative effects on behavioral, biochemical, proinflammatory cytokines, and histopathological studies as compared with the BCCA group. Whereas, the combination group showed a significant difference in ameliorating the pathological changes of biochemical parameters and histopathological changes in comparison with the PPX alone treated group but not with the NAC alone group.
The study concluded that in the combination treatment group the histopathological parameter improved and the oxidative stress parameters were mitigated significantly compared with the PPX alone treatment group but not with the NAC alone treatment group.

The current study was conducted to examine the possible protective and retentive effects of one-week intra-peritoneal (IP) administration of selenium nanoparticles (Se-NPs), compared to its bulk counterpart, selenite sodium (Ss), after one complete cycle of spermatogenesis in mature male mice.
Thirty adult male mice were divided into 3 groups. Control group was administrated phosphate-buffered saline (IP) and the other groups received Ss (0.50 mg kg-1) and Se-NPs (0.50 mg kg-1) for seven successive days. Then, the animals were monitored for 28 days and finally sacrificed and tissue and blood samples were taken. Histopathological features, sperm quality, in vitro fertilization (IVF) capability and selenium (Se) content in testicular tissue were analyzed. Antioxidant enzyme activities including catalase, glutathione peroxidase, and superoxide dismutase as well as total antioxidant capacity and malondialdehyde levels were assessed in blood and the tissue samples.
Remarkable differences were found in sperm characteristics, histopathological features and oxidative stress biomarkers between control and treatment groups. Moreover, IVF evaluation and tissue Se concentration examination weren’t similar for Se-NPs and Ss.
Conclusively, Se-treated groups had more antioxidant capacity than the control group, but sperm quality and histopathological features revealed that Se-NPs might possess more antioxidative and retentive potential compared to Ss in one spermatogenesis cycle.

There are controversial results regarding the effect of the interaction of CETP polymorphisms with dietary fats on the lipid profiles. The aim of this study was to examine the effect of CETP polymorphisms (rs5882 and rs3764261) and macronutrient intakes interaction in relation to metabolic syndrome (MetS) or its components.
In this nested case-control study, subjects were selected from among participants of the Tehran Lipid and Glucose Study. Cases (n=441) were individually matched with two controls (844 non-MetS subjects). DNA samples were genotyped with HumanOmniExpress-24-v1-0 bead chips, including 649,932 SNP loci.
The mean ages at baseline were 38.1±10 and 37.0±10 years in women and 36.2±11 and 36.3±11 years in men, respectively in cases and controls. We did not find significant gene-diet interactions between rs5882 and dietary macronutrient intakes in relation to MetS risk. The risk of low HDL-C was lower in the first quartile of MUFA and total fat intake in G allele carriers, compared to AA genotype group. The risk of high BP appeared to increase significantly in higher quartiles of trans-fatty acid intakes (>1.81% of total energy intake) in G allele carriers compared with the AA genotype group. No significant interactions were found between rs3764261 and macronutrient intakes in association with MetS or its components.
Our findings demonstrate that dietary fats modify the association of rs5882 and risk of low HDL-C and high blood pressure.

The aim of the present study is to investigate probable acute effects of vitamin D on ischemia-reperfusion injury in the rat ovary.
A group of 30 Wistar albino rats was divided into five groups of 6 each. Group 1: underwent laparotomy only and the ovaries were removed. Group 2: 3-hr ischemia followed by excision of the ovaries. Group 3: 3-hr ischemia and 3-hr reperfusion and the ovaries were removed. Group 4: vitamin D was administered 30 min prior to the 3-hr of ischemia and the ovaries were excised at the end of ischemia period. Group 5: vitamin D was administered 30 min prior to the 3-hr of ischemia and 3-hr reperfusion then the ovaries were removed at the end of reperfusion. The ovaries excised in each group also underwent biochemical and histopathologic analysis. MDA (malondialdehyde), SOD (superoxide dismutase), NO (nitric oxide), TAS (total antioxidant score), TOS (total oxidant score) were analyzed as biochemical parameters.
There were no significant differences between groups in TAS, TOS, or OSI (P>0.05). MDA levels were lower in the vitamin D treatment groups especially in group 5, significantly (P Vitamin D seems an effective molecule for protection of ischemia-reperfusion injury in rat ovary. There is some significant improvement in oxidative damages with vitamin D treatment.

We investigated the role of nitric oxide (NO) in the protective effects of remote ischemic per-conditioning (rIPerC) on renal ischemia/reperfusion (I/R) injury in male rats.
I/R treatment consisted of 45 min bilateral renal artery ischemia and 24 hr reperfusion interval. rIPerC was performed using four cycles of 2 min occlusions of the left femoral artery and 3 min reperfusion at the beginning of renal ischemia. The animals were given normal saline (vehicle), NG-nitro-L-arginine methyl ester (L-NAME) or L-arginine. Following the reperfusion period, renal functional- and oxidative stress- parameters, as well as histopathological changes were assessed.
In comparison with the sham group, I/R resulted in renal dysfunction, as indicated by significantly lower creatinine clearance and higher fractional excretion of sodium. This went along with decreased glutathione peroxidase (GPX) and catalase (CAT) activity in the I/R group, increased malondialdehyde (MDA) contents and histological damages. In comparison with the I/R group, the rIPerC group displayed improved renal function, increased activity of GPX and CAT enzymes, and decreased MDA level. However, these effects were abrogated by L-NAME injection and augmented by L-arginine treatment.
According to the results, the functional and structural consequences of rIPerC against I/R-induced kidney dysfunction, which is associated with reduction of lipid peroxidation and intensification of anti-oxidant systems, is partially dependent on NO production.

Cisplatin (CP), as an anti-neoplastic drug, causes testicular damage. Zataria multiflora Boiss (ZM), a medicinal plant, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of ZM against CP-induced testicular toxicity.
In this experimental study, thirty-two adult male mice were randomly divided into four groups. The control group received normal saline with oral gavage during 7 days; ZM group received ZM (200 mg/kg) during 7 days by gavage; CP group received CP (10 mg/kg) intraperitoneally (IP) in the 5th day of study; ZM CP group received ZM during 7 days and CP was injected in 5th day. Sperm parameters, biochemical (MDA, GSH, and PC) levels, serum testosterone levels, and histopathological and immunohistochemical assays of testis were examined one day after the last drug treatment.
CP treatment caused significant damage via changed sperm parameters (sperm motility, count, viability rate, and abnormalities), increased oxidative stress (increased MDA and PC levels, and decreased GSH level), histological changes (degeneration, necrosis, arrest of spermatogenesis, congestion, and decrease in thickness of the germinal epithelium, diameter of seminiferous tubules, and Johnsen’s Score), decreased serum testosterone level, and increased caspase-3 immunoreactivity. ZM preserved spermatogenesis and mitigated the toxic effects of CP on the testis tissue. In addition, treatment with ZM significantly reduced caspase-3 immunoreactivity.
The findings of this study suggest that ZM as a potential antioxidant compound and due to free radicals scavenging activities has a protective effect against CP-induced testicular toxicity.

Neuroprotection is created following the inhibition of angiotensin II type 1 receptor (AT1R). Therefore, the purpose of this research was examining AT1R blockage by candesartan in diffuse traumatic brain injury (TBI).
Male rats were assigned into sham, TBI, vehicle, and candesartan groups. Candesartan (0.3 mg/kg) or vehicle was administered IP, 30 min post-TBI. Brain water and Evans blue contents were determined, 24 and 5 hr after TBI, respectively. Intracranial pressure (ICP) and neurologic outcome were evaluated at -1, 1, 4 and 24 hr after TBI. Oxidant index [malondialdehyde (MDA)] was determined 24 hr after TBI.
Brain water and Evans blue contents, and MDA and ICP levels increased in TBI and vehicle groups in comparison with the sham group. Candesartan attenuated the TBI-induced brain water and Evans blue contents, and ICP and MDA enhancement. The neurologic score enhanced following candesartan administration, 24 hr after TBI.
The blockage of AT1R may be neuroprotective by decreasing ICP associated with the reduction of lipid peroxidation, brain edema, and blood-brain barrier (BBB) permeability, which led to the improvement of neurologic outcome.

The stress-responsive genes of Sestrin family are recognized as new tumor suppressor genes in breast carcinoma, however, the function of Sestrin family in human prostate cancer is not clear. Ionizing radiation (IR) is known to induce Sestrin gene expression in breast cancer cells. However, the response of Sestrin to IR has not been reported in PC3 prostate cancer cells.
Sestrin2 expression in prostate cancer cell lines (PC3, LNCaP clone FGC, and DU145) was detected by Western blot and real-time PCR. Cell counting kit (CCK-8) was used to detect cellular proliferation. The radiosensitivity of PC3 cells was detected by clonogenic assay.
Sestrin2 expression in prostate cancer cell lines (PC3, LNCaP clone FGC, and DU145) is low. In vitro assays indicated that over-expressing Sestrin2 in human prostate cancer PC3 inhibited tumor proliferation. In addition, elevated Sestrin2 expression sensitized PC3 cells to IR.
We determined Sestrin2 may function as a tumor suppressor through repressing proliferation, mediating sensitization to IR in PC3 cells.

Growing evidence demonstrates that L-arginine/NO/cGMP/KATP channel pathway has a modulatory role in pain perception. Previous studies have shown that thymoquinone exerts antinociceptive effects; however, the mechanisms underlying antinociception induced by thymoquinone have not been fully clarified. The aim of the present study was to evaluate the role of L-arginine/NO/cGMP/KATP channel pathway in the central and peripheral antinociceptive effect of thymoquinone in rats.
Rats were pretreated intraplantarly (IPL) or intracerebroventricularly (ICV) with L-arginine (the NO precursor), l-NAME (an NO synthase inhibitor), SNAP (an NO donor), methylene blue (a guanylyl cyclase inhibitor), glibenclamide (the blocker of KATP channel), and tetraethylammonium (TEA, a Kv channel blocker) before the injection of thymoquinone.
Local ipsilateral (20 and 40 μg, IPL) but not contralateral and ICV (4 and 8 μg) administration of thymoquinone caused a dose-dependent and significant antinociception in both early and late phases of the formalin test. Pretreatment of rats with L-arginine (100 μg, IPL or ICV) and SNAP (200 μg, IPL or ICV) increased while l-NAME (100 μg, IPL or 1 μg, ICV) and methylene blue (400 μg, IPL or ICV) decreased the antinociceptive effects of thymoquinone in the formalin test. The administration of TEA (IPL or ICV) did not modify but glibenclamide (50 μg, IPL or ICV) significantly abolished the peripheral and central antinociceptive effects of thymoquinone in both phases of the formalin test.
The results of the present study indicate that L-arginine/NO/cGMP/KATP channel pathway participates in the central and peripheral antinociceptive effect of thymoquinone.

To investigate the role of autophagy in advanced glycation end products (AGEs)-induced proliferation and migration in rat vascular smooth muscle cells (VSMCs).
After culture, VSMCs were treated with 0, 1, 10, and 100 μg/ml concentrations of AGEs. Autophagy specific protein light chain 3 (LC3)-I/II was determined by western blotting, autophagosomes were observed with electron microscopy, cell proliferation was quantified using the methyl thiazolyl tetrazolium (MTT) assay, and cell migration was evaluated using Transwell migration and scratch assays.
Compared to the control group, the level of LC3- II/I in AGEs treatment group was up-regulated, and the number of autophagosomes was also increased. Furthermore, in concentration of 100 μg/ml AGEs, the extent of proliferation and migration was significantly increased compared to the control group. However, pretreating cells with autophagy inhibitor 3-MA could attenuate these effects.
Our study demonstrated that AGEs-induced autophagy accelerated AGEs-stimulated proliferation and migration in VSMCs.

Nicotine as a toxic substance leads to impairment of the reproductive system function. The aim of this study was to evaluate effects of melatonin on testicular alterations, sperm nuclear integrity, and epididymal sperm parameters in mice treated with nicotine.
Male mice were divided into four groups. Group A received the vehicle, group B received nicotine 0.1 mg/100 g BW, group C received melatonin 10 mg/kg, group D received nicotine plus melatonin. Evaluations were made by histology and Johnson’s score for study of spermatogenesis, immunostaining for study of male germ cells apoptosis, sperm chromatin dispersion (SCD) test for assaying sperm chromatin integrity, enzyme-linked immunosorbent assay (ELISA) for assessment of serum levels of testosterone and luteinizing hormone (LH), and sperm parameters including morphology, motility, and count.
Nicotine caused a significant decrease in spermatogenesis quantity and Johnson’s score, sperm parameters, and sex hormones. Melatonin in group D, increased sperm chromatin integrity, improved spermatogenesis, Johnson’s score, and sperm parameters (P this study showed administration of melatonin in nicotine-treated mice increases both quality and quantity of spermatogenesis and integrity of sperm’s chromatin through reducing apoptosis and modifying the testosterone level.

Herbal medicines are an alternative choice for treatment or controlling of polycystic ovary syndrome (PCOS). Effect of hydroalcoholic extract of flaxseed was evaluated on ovarian hormones and histological changes of uterus and ovary in a PCOS-induced rat model.
Twenty four rats divided into four groups including negative control, positive control, PCOS and treatment groups. Positive control group received hydroalcoholic extract of flaxseed for 30 days. PCOS was induced by single intramuscular injection of estradiol valerate. Treatment group was treated with flaxseed extract 7 weeks after induction of PCOS for 30 days. Ovaries and uterus were dissected out and their sections were used for histomorphometric study. Levels of estradiol, progesterone, testosterone and dehydroepiandrosterone (DHEA) were measured in the serum.
In the treatment group, flaxseed extract increased level of progesterone (P Hormonal profile and histomorphometric features of ovary that were disturbed by PCOS induction were ameliorated by hydroalcoholic extract of flaxseed.