Obestatin inhibits apoptosis and astrogliosis of hippocampal neurons following global cerebral ischemia reperfusion via antioxidant and anti-inflammatory mechanisms

Objective(s): Obestatin is a newly discovered peptide with antioxidant activities in different animal models. Recent studies have shown that Obestatin inhibits apoptosis following cardiac ischemia/reperfusion injury. Brain ischemia/reperfusion induces irreversible damage especially in the hippocampus area. This study aimed at examining the protective impact of Obestatin on apoptosis, protein expression and reactive astrogliosis level in hippocampal CA1 region of rat following transient global cerebral ischemia.Materials and Methods: Forty-eight male Wistar rats were randomly assigned into 4 groups (sham, ischemia/reperfusion, ischemia/reperfusion+ Obestatin 1, and 5 µg/kg, n=12). Ischemia induced occlusion of both common carotid arteries for 20 min. Obestatin 1 and 5 µg/kg were injected intraperitoneally at the beginning of reperfusion period and 24 and 48 hr after reperfusion. Assessment of the antioxidant enzymes and tumor necrosis factor alpha (TNF-α) was performed by ELISA method. Caspase-3 and glial fibrillary acidic protein (GFAP) proteins expression levels were evaluated by immunohistochemical staining 7 days after ischemia.Results: Based on the result of the current study, lower superoxide dismutase (SOD) and glutathione (GSH) (

Differential Expression of CD16 and CD56 on Natural Killer (NK) Cell Subsets in Multiple Sclerosis and Neuromyelitis Optica

Background: Multiple sclerosis (MS) and Neuromyelitis optica (NMO) are inflammatory and demyelinating diseases of the central nervous system (CNS). NK cells are supposed to play an important role in the pathophysiology of MS, but their role in the NMO remains unknown. The aim of this study was to compare the prevalence of different subpopulations of NK cells in the patients with MS and NMO and healthy individuals. Methods: Treatment Naive MS and NMO patients, age, and sex matched controls were included in this study. PBMCs were isolated from peripheral blood and different phenotypes of circulating NK cells were compared with the flow cytometry analysis. Results: There were no significant differences in the mean percentages of circulating NK cells expressing the CD56 bright molecule in patients with MS and NMO. However, the mean percentages of circulating NK cells expressing the CD56bright molecule were significantly lower in all patients groups, compared to controls. In addition, the mean percentages of circulating NK cells expressing the CD16dim molecule was significantly higher in the patients with MS, compared to controls/any other groups. The mean percentages of circulating NK cells expressing the CD56dim molecule were significantly higher in the patients with MS than the controls. There were significant differences in the mean percentages of circulating NK cells expressing the CD16bright molecule between the patients with MS, and NMO/controls. Conclusions: The results indicate that evaluation of NK cell subsets has an implication for the biomarker discovery and therapeutic targets in given diseases

Differential Expression of CD16 and CD56 on Natural Killer (NK) Cell Subsets in Multiple Sclerosis and Neuromyelitis Optica

Background: Multiple sclerosis (MS) and Neuromyelitis optica (NMO) are inflammatory and demyelinating diseases of the central nervous system (CNS). NK cells are supposed to play an important role in the pathophysiology of MS, but their role in the NMO remains unknown. The aim of this study was to compare the prevalence of different subpopulations of NK cells in the patients with MS and NMO and healthy individuals. Methods: Treatment Naive MS and NMO patients, age, and sex matched controls were included in this study. PBMCs were isolated from peripheral blood and different phenotypes of circulating NK cells were compared with the flow cytometry analysis. Results: There were no significant differences in the mean percentages of circulating NK cells expressing the CD56 bright molecule in patients with MS and NMO. However, the mean percentages of circulating NK cells expressing the CD56bright molecule were significantly lower in all patients groups, compared to controls. In addition, the mean percentages of circulating NK cells expressing the CD16dim molecule was significantly higher in the patients with MS, compared to controls/any other groups. The mean percentages of circulating NK cells expressing the CD56dim molecule were significantly higher in the patients with MS than the controls. There were significant differences in the mean percentages of circulating NK cells expressing the CD16bright molecule between the patients with MS, and NMO/controls. Conclusions: The results indicate that evaluation of NK cell subsets has an implication for the biomarker discovery and therapeutic targets in given diseases

Time- and Dose-Dependent Neuroprotective Effects of Sex Steroid Hormones on Inflammatory Cytokines after a Traumatic Brain Injury

Following a traumatic brain injury (TBI), excessive release of proinflammatory cytokines is the major cause of cerebral edema and neuronal loss. This study was designed to examine changes in concentrations of some proinflammatory cytokines—including interleukin-1 beta (IL-1b), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-a), and transforming growth factor-beta (TGF-b)—in a rat model of TBI in which the animals were treated with different doses of estrogen or progesterone 6 and 24 h after the TBI. Adult female rats were divided into 14 groups. Hormones or vehicle were given intraperitoneally 30 min after a moderate TBI was induced by the Marmarou method. The levels of proinflammatory cytokines in brain were measured at 6 and 24 h after the TBI. A high dose of estrogen (E2) or a low dose of progesterone (P1) increased brain levels of IL-1b 52.7% and 79.2% respectively at 6 h after the TBI. By 24h, IL-1b levels in the brain were 27.5% and 27% lower following administration of estrogen low dose (E1) or E2, respectively. High-dose administration of progesterone reduced brain levels of IL-6 to 45.9% at 6 h after the TBI, and P1 and E1 treatment significantly decreased IL-6 levels at 24 h. Brain levels of TNF-a were 72.5% lower at 6 h after the TBI following P2 treatment and 48.5% higher at 24 hrs following treatment with E2. The levels of TGF-b were also 3.37 times higher 24 h after the TBI following treatment with E1. Both doses of the hormones tested increases TGF-b levels 6 h after the TBI. Based on our findings, we conclude that progesterone and estrogen influence the levels of proinflammatory cytokines either at the primary or secondary stages after a TBI. Accordingly, this study suggests a mechanism by which hormones reduce cerebral edema

Sulfur dioxide reduces hippocampal cells death and improves learning and memory deficits in rat model of transient global ischemia/reperfusion

Objective(s): According to recent the findings, sulfur dioxide (SO2) is produced by the cardiovascular system, influencing some major biological processes. Based on previous research, SO2 exhibits antioxidant effects and inhibits apoptosis following cardiac ischemia/reperfusion. Therefore, the objective of the current study was to examine the neuroprotective impact of SO2 following global cerebral ischemia/reperfusion (I/R).Materials and Methods: Forty-eight male Wistar rats that weighed 260–300 g, were randomly allocated into 4 groups: sham group (n=12), I/R group (n=12), and I/R+SO2 groups (NaHSO3 and Na2SO3; 1:3 ratio; 5 and 10 µg/kg, respectively; for 3 days, n=12). Cerebral ischemia model was prepared by occlusion of both common carotid arteries for 20 min. Saline as a vehicle and SO2 donor at doses 5 µg/kg (intraperitoneally) were injected for 3 days after reperfusion. Four days after ischemia, the passive avoidance memory test was carried out in four groups, and after behavioral assessment, necrosis, apoptosis, and antioxidant enzyme analysis were carried out.Results: SO2 treatment could significantly improve memory impairments in rats with cerebral ischemia/reperfusion (I/R) (

What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?

To permit appropriate targeted therapy, the present clinical studywas aimed to investigate the effects of progesterone on the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury (DAI). Forty-eightmaleDAI patients were divided into two groups (control and progesterone). Progesterone group received progesterone in dose of 1 mg/kg per 12 h for five days. The outcome was investigated using Extended Glasgow Outcome Scale (GOS-E) and functional independencemeasure (FIM). Themarkers of inflammation [interleukin-1β (IL-1β), IL-6, transforming growth factor-β1 (TGF-β1)], injury (brain protein of S-100B), and oxidant activity [malondialdehyde (MDA)] were evaluated in the serum of the patients. Higher GOS-E and FIMscoreswere observed in progesterone group at the six-month follow-up (P b 0.05 and P b 0.01, respectively). Meanwhile, a reduction in the serum levels of IL-1β, MDA and S-100B was noticed in progesterone group 24 h after injury (P b 0.05, P b 0.001 and P b 0.05, respectively), and there was an increase in serum levels of IL-6 and TGF-β1 (P b 0.01 and P b 0.05, respectively). Also, lower levels of MDA and S-100B, and higher levels of TGF-β1were observed in progesterone group six days after injury (P b 0.05). According to these findings, progesterone may improve the outcome in DAI patients probably through modulation in the levels of cytokines, and reduction in the injury and oxidant activity

Effect of Kudzu Root (Pueraria lobata) on Testis of Streptozotocin Induced Diabetic Rats

Background & objectives: Diabetes mellitus mediated by oxidative stress, creates serious metabolic disorders in testis. Kudzu root with an isoflavonin and saponin contents is often used as antidiabetic and antioxidant. This study aimed at preventing the oxidative effects of diabetes using Kudzu root. Methods: In this study, 32 male Wistar rats were randomly selected and divided into four groups: control, diabetic and diabetic rats treated with Kudzu 50 and100 mg/kg. Diabetes was induced by intraperitoneal injection of 55mg/kg streptozocin. One week after injection, the rats started to receive Kudzu at the doses of 50 and 100 mg/kg for five weeks by gavage. Testicular damage was examined by using hematoxylin-eosin staining protocol. Hormonal and blood biochemical factors were measured. Results: The results of this study showed that diabetes causes a high blood sugar levels and reduces the spermatogonia and Sertoli cells with decreased spermatogenesis,sperm count and function. These effects were improved in the treatment groups. Decrease in blood sugar and increase in the number and motility of sperm cells and spermatogonic cells were also observed together with enhanced seminiferous tubule diameter and lower basement membrane thickness. Conclusion: Kudzu with the ability to reduce blood sugar, improves diabetic-induced testicular damage and can have a therapeutic role in diabetes.

Protective Effects of Nucleobinding-2 After Cerebral Ischemia Via Modulating Bcl-2/Bax Ratio and Reducing Glial Fibrillary Acid Protein Expression

Introduction: Nucleobinding-2 (NUCB2) or nesfatin-1, a newly identified anorexigenic peptide, has antioxidant, anti-inflammatory, and anti-apoptotic properties. Brain ischemia-reperfusion induces irreversible damages, especially in the hippocampus area. However, the therapeutic effects of NUCB2 have not been well investigated in cerebral ischemia. This study was designed for the first time to investigate the protective effects of NUCB2/Nesfatin-1 on the expression of apoptosis-related proteins and reactive astrogliosis level in the CA1 area of hippocampus in an experimental model of transient global cerebral ischemia. Methods: The male Wistar rats were randomly allocated into 4 groups (sham, NUCB2, ischemia-reperfusion, and ischemia-reperfusion+NUCB21) (n =7). The model of cerebral ischemia was prepared by common carotid arteries occlusion for 20 minutes. Nesfatin-1 (20 µg/kg) and saline (as a vehicle) were injected (intraperitoneally) at the beginning of the reperfusion period. The assessment of the protein expression levels was performed by immunofluorescence and immunohistochemical staining. Results: NUCB2 significantly reduced the Bax and GFAP protein levels in the CA1 area after ischemia (P<0.05). Also, NUCB2 increased Bcl-2 protein level (P<0.05). NUCB2 exerted protective effects against ischemic injury by the inhibition of astrocytes activation as an inflammatory response and decreased neuronal cell apoptosis. Conclusion: The present study provides the possible neuroprotective view of nesfatin-1 in the treatment of ischemia injury model in rat hippocampus

Neuroprotective Effects of Berberine Hydrochloride on Methamphetamine-induced Cognitive Dysfunction: Immunohistochemical and Behavioral Studies in Rats

Introduction: Methamphetamine (MA) as an addictive psychostimulant drug affects the central nervous system. The current research aimed to evaluate the impact of berberine hydrochloride on improving cognitive function and neuroprotective effects in rats addicted to MA. Methods: In this study, 27 male Wistar rats were randomly assigned to three groups, including control, MA addiction, and MA addiction with berberine hydrochloride (100 mg/kg/d) orally during the three weeks of withdrawal. Two groups received self-administered inhaled MA for two weeks (up to 10 mg/kg). Following the experimental procedures, a Morris water maze (MWM) and shuttle box were used to assess memory, and hippocampal sections from the animals were examined for caspase-3, Ki-67, and glial fibrillary acidic protein (GFAP) expression. Results: The obtained results from the Morris water maze (MWM) showed that berberine hydrochloride decreases (P<0.01) the distance moved and the time spent to reach the hidden platform in the four-day learning trails phase and significant differences were observed in the distance moved, spent time, and frequency of motion in target quadrant on probe test day between groups. Berberine hydrochloride also reduced the latency of animals entering the dark chamber in the treated group compared to the control group (P<0.05). A significant decrease in activation of caspases-3, higher percentages of Ki-67 expression, and an increase in glial fibrillary acidic protein (GFAP) expression of cells was observed in the addicted group compared to the berberine-treated and control groups (P<0.05). Conclusion: Administration of berberine hydrochloride for 3 weeks improves cognitive function in MA addiction and it has potential neuroprotective efficacy

Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction through occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration