Testosterone enhances functional recovery after stroke through promotion of antioxidant defenses, BDNF levels and neurogenesis in male rats

Purpose: This study was aimed to evaluate the antioxidant and anti-inflammatory effects of vitamin D and Simvastatin (SIM) on a high-fat diet (HFD) induced-obese rats. Methods: 40 adult male rats were divided into four groups: control group, HFD, HFD + vitamin D, and HFD + SIM for 14 weeks. Vitamin D or SIM supplementation was done for the last 6 weeks. Vitamin D dosage was 500 IU/kg, while SIM dosage was 10 mg/kg. Interleukin-6 (IL-6) concentration and markers of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione(GSH) concentrations in serum were determined using ELISA kits and spectrophotometry methods, respectively. Results: Treatment with vitamin D or SIM could significantly reduce IL-6 and MDA and increases SOD, GPx activities, and GSH levels. Oxidative stress can result not only from increased ROS production but also from dysfunctional antioxidant defenses. Conclusion: From the experimental results, it was observed that SIM and vitamin D could attenuate oxidative stress and inflammation markers associated with obesity.

Download Full-text

Therapeutic effect of thiocetam on the manifestations of ischemia-reperfusion complicated by massive blood loss and mechanical trauma

Journal of Education, Health and Sport ◽

10.12775/jehs.2020.10.12.038 ◽

2020 ◽

Vol 10 (12) ◽

pp. 382-393

Author(s):

Nataliya Volotovska

Keyword(s):

Blood Loss ◽

Ischemia Reperfusion ◽

White Male ◽

Early Period ◽

Male Rats ◽

Antioxidant Defenses ◽

Mechanical Trauma ◽

Massive Blood Loss ◽

Post Traumatic ◽

Positive Effect

Among the current medical and social problems, injuries and blood loss occupy a prominent place, causing stress on the antioxidant defenses. Hypoxia, which underlies the pathogenesis of the post-traumatic period of both diseases, leads to a significant imbalance in the work of internal organs. Scientists are increasingly attracted by the need to use a tourniquet or intraoperative ligatures, as reperfusion local and systemic damage develops. Antioxidants are considered a promising means of correction.The aim of the study was to investigate the features of metabolic disorders in the liver in the early post-traumatic period on the background of the use of a tourniquet and the effectiveness of thiocetam correction.Materials and methods. The experiment was perfomed on 130 white male rats (200-250 g), which were divided into 4 groups: control – the CG, the EG-1 – combination of limb ischemia-reperfusion (IR) with blood loss, the EG-2 – combination of limb IR with blood loss and mechanical trauma of the thigh; the EG-3 combination of limb IR, blood loss, mechanical injury and thiocetam administration. The Malonic dialdehide level catalase activity were estimated in the liver.Results. The use of thiocetam, which is able to struggle against of ischemia and lipid peroxidation by reactivating antiradical enzymes: superoxide dismutase, catalase and glutathione peroxidase, had a positive effect on the state of antioxidant and prooxidant units in the organ, located far from the place of primary ischemia-reperfusion. If in the group of untrated animals (the EG-2, where massive blood loss was combined with a thigh fracture and the use of hemostatic tourniquet) in the early period, the MDA level exceeded the CG data in 5,4 times, and on the 7th and 14th days remained high – being higher on 2,1 times and on 2,7 times, then in the EG-3 (group of treated animals) on the 1st day the level of MDA exceeded the CG data in 4,3 times, but on the 7th and 14th days was higher by 90,5 % and 64 % respectively. The supportive effect of thiocetam on the activity of catalase in the liver was also noted. Thus, in EG-2 the level of antioxidant enzyme on the 1st day decreased by 71,7 %, and remained almost at this level throughout the all post-experimental period. As for the group of treated animals, the level of activity on the 1st day after the intervention decreased by 44,7%, and was so for almost the entire period. On the 14th day, it remained reduced compared to the CG by 35,1 %, while in EG-2 this index was lower compared to the CG by 70,5 %.Conclusion. Having the positive effect of the introduction of thiocetam in the ischemic area, we can eventually add new complex, given the world experience, which would affect the development of the inflammatory response and the rheological properties of blood.

Download Full-text

Abstract 2741: S-Nitrosoglutathione Increases Benefit of Motor Exercise on Functional Recovery and Stimulates Neurorepair Mechanisms Following Experimental Stroke in Rats

Stroke ◽

10.1161/str.43.suppl_1.a2741 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Mushfiquddin Khan ◽

Harutoshi Sakakima ◽

Tajinder S Dhammu ◽

Shunmugavel Anandakumar ◽

Inderjit Singh ◽

...

Keyword(s):

Cell Death ◽

Functional Recovery ◽

Neurotrophic Factors ◽

Neuronal Cell ◽

Male Rats ◽

Experimental Stroke ◽

Protective Agent ◽

Neurobehavioral Function ◽

Long Term Treatment

Background: Stroke is the leading cause of long-term physical disability and life-long neurologic deficits. The disability stems from acute neurovascular injury and injury-induced compromised neuroplasticity. This neuroplasticity can be restored by stimulating neurotrophic factors via two possible modalities: rehabilitation activity and neurorepair therapy. Improvement of neurologic function has been achieved following brain trauma by the neurovascular protective agent S-nitrosoglutathione (GSNO). Therefore, we investigated whether GSNO stimulates the expression neurotrophic factors and enhances the benefits of motor exercise, leading to functional recovery in a rat model of experimental stroke. Methods: Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 60 min followed by reperfusion in adult male rats. Injured animals were either treated with vehicle (IR group), GSNO (0.25 mg/kg, GSNO group) or underwent rotarod exercise (EX group). In the third treatment group, GSNO was combined with rotarod exercise (GSNO+EX group). The groups were compared in terms of brain infarction, neurological score, motor function, cell death, tissue structure, and the expression of the neurotrophic factors BDNF, TrKB, and myelin. Results: All three treated groups (GSNO, EX and GSNO+EX) showed reduced infarction, improved motor and neurological functions, and decreased apoptotic neuronal cell death compared to the IR group. However, the combination group GSNO+EX showed a trend toward greater recovery than the GSNO or EX group alone. All the three treated groups also showed enhanced expression of neurotrophic factors and improved tissue histology. A delayed intervention (24 h after IR) by GSNO also aided the functional recovery. Furthermore, the protective effect of GSNO and exercise was blunted in another set of animals by an inhibition of AKT activity using the PI3 kinase inhibitor LY 294002 compound. Conclusion: GSNO, like exercise, aids recovery of functions in a long-term treatment by stimulating the expression of neurotrophic factors, reducing infarctions, and decreasing cell death. A combination of exercise and GSNO shows a greater degree of improvement in neurobehavioral function. Clinical relevance of the therapy is supported by an improved functional recovery even when GSNO was administered 24 h following IR. Mechanistically, the improvements by GSNO and exercise are dependent, at least in part, on AKT activity.

Download Full-text

Abstract 351: Allogeneic C-kit + Cardiac Progenitor Cells are Immune Tolerant With Strong Efficacy for Cardiac Functional Recovery

Circulation Research ◽

10.1161/res.119.suppl_1.351 ◽

2016 ◽

Vol 119 (suppl_1) ◽

Author(s):

Srinivasa Raju Datla ◽

Yin Guo ◽

Rachana Mishra ◽

Ling Chen ◽

Progyaparamita Saha ◽

...

Keyword(s):

Inflammatory Response ◽

Progenitor Cells ◽

Functional Recovery ◽

Female Rats ◽

Male Rats ◽

Right Atrial ◽

Cardiac Progenitor Cells ◽

Cardiac Recovery ◽

Immune Tolerant ◽

Inbred Rat

Background: A recent clinical trail using adult autologous c-kit + cardiac progenitor cells (c-kit + CPCs) have demonstrated cardiac functional recovery in myocardial ischemic patients. This autologous approach of ex vivo expansion of c-kit+ CPCs is expensive and time consuming. The immune tolerant properties of c-kit + CPCs have not been investigated as an alternative clinical strategy. In this study, we compared allogeneic and syngeneic c-kit + CPCs immunogenic tolerance and cardiac recovery potentials using divergent inbred rat strains in a myocardial infarction (MI) model. Methods and Results: We isolated rat c-kit + CPCs (rc-kit + CPCs) from male Wistar Kyoto (WKY) rat hearts and human c-kit + CPCs (hc-kit + CPCs) from adult coronary artery bypass graft patient’s right atrial appendage. In vitro, both rat and human c-kit + CPCs expressed MHC class I but not class II or co-stimulatory molecules CD80 and CD86. In mixed lymphocyte reaction (MLR) assay, allogeneic and syngeneic rc-kit + CPCs elicited minimal T-cell proliferation. In vivo, intra-myocardial administration of WKY rc-kit + CPCs after creating MI condition, elicited minimal local, systemic and humoral inflammatory response in allogeneic (Brown Norway (BN) female rats) and syngeneic (WKY female rats) groups compared to the xenogeneic (hc-kit + CPCs in BN male rats). In addition, the allogeneic and syngeneic rc-kit + CPCs groups significantly recovered cardiac function (EF, SV, and CO) compared to the xenogeneic c-kit + CPCs group, which had no functional recoverability. Histological analysis further revealed that allogeneic and syngeneic rc-kit + CPCs groups had significantly decreased scar size by increasing endogenous cardiomyocyte proliferation, c-kit + CPC recruitment and increased neoangiogenesis. Conclusion: Allogeneic c-kit + CPCs are immune tolerant and produce minimal inflammatory response while maintaining their cardiac recovery potentials in immunologically divergent species. Our observation, for the fist time, reports the minimal immunogenic response by c-kit + CPCs and strongly supports the development of an allogeneic c-kit + CPC strategy for clinical trial applications.

Download Full-text

High-Dose Testosterone Propionate Treatment Reverses the Effects of Endurance Training on Myocardial Antioxidant Defenses in Adolescent Male Rats

Cardiovascular Toxicology ◽

10.1007/s12012-011-9105-3 ◽

2011 ◽

Vol 11 (2) ◽

pp. 118-127 ◽

Cited By ~ 21

Author(s):

Ewa Sadowska-Krępa ◽

Barbara Kłapcińska ◽

Sławomir Jagsz ◽

Andrzej Sobczak ◽

Stanisław J. Chrapusta ◽

...

Keyword(s):

Endurance Training ◽

Testosterone Propionate ◽

Male Rats ◽

Antioxidant Defenses ◽

Adolescent Male ◽

High Dose

Download Full-text

JNK-IN-8, a c-Jun N-terminal kinase inhibitor, improves functional recovery through suppressing neuroinflammation in ischemic stroke

10.1101/449496 ◽

2018 ◽

Cited By ~ 1

Author(s):

Hongli Tang ◽

Qinxue Dai ◽

Wandong Hong ◽

Kunyuan Han ◽

Danyun Jia ◽

...

Keyword(s):

Ischemic Stroke ◽

Brain Injury ◽

Functional Recovery ◽

Kinase Inhibitor ◽

Neurological Function ◽

Mitogen Activated Protein Kinase ◽

Male Rats ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Tnf Α

Abstractc-Jun N-terminal kinase (JNK), a mitogen activated protein kinase, is activated in ischemia brain injury and plays an important role in cerebral ischemic injury. Emerging studies demonstrated that JNK-IN-8 (a specific JNK inhibitor) regulates traumatic brain injury through controlling neuronal apoptosis and inflammation. However, the role of JNK-IN-8 in ischemic stroke and the underlying mechanisms of JNK-IN-8 involving neuroprotection remain poorly understood. In the present study, male rats were subjected to tMCAO (transient middle cerebral artery occlusion) followed by treatment with JNK-IN-8, and then the modified improved neurological function score (mNSS), the Foot-fault test and the level of inflammatory cytokines (IL-1β, IL-6 and TNF-α) were assessed. We found that JNK-IN-8-treated rats with MCAO exerted a significant improvement in spatial learning as measured by the improved mNSS, and showed sensorimotor functional recovery as measured by the Foot-fault test. JNK-IN-8 also exerted anti-inflammatory effects as indicated by decreased activation of microglia and the decreased expresson of IL-6, IL-1β and TNF-α. Furthermore, JNK-IN-8 suppressed the activation of JNK and subsequent activation of NF-κB signaling as indicated by the decreased level of phosphorylated JNK (p-JNK) and p65. These data suggest that JNK-IN-8 suppressed neuroinflammation and improved neurological function by inhibiting JNK/NF-κB pathway after ischemic brain injury, thus offering a new target for prevention of ischemic brain injury.

Download Full-text

ANTIOXIDANT AND HEPATOPROTECTIVE EFFECTS OF VIRGIN COCONUT OIL AT MAXIMUM PHYSICAL ACTIVITY

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i3.30299 ◽

2019 ◽

pp. 272-276 ◽

Cited By ~ 2

Author(s):

FAJAR APOLLO SINAGA ◽

URIP HARAHAP ◽

JANSEN SILALAHI ◽

HERBERT SIPAHUTAR

Keyword(s):

Oxidative Stress ◽

Physical Activity ◽

Transaminase Level ◽

Coconut Oil ◽

Male Rats ◽

Antioxidant Defenses ◽

Control Group ◽

Time To Exhaustion ◽

Protective Effects ◽

Virgin Coconut Oil

Objective: The purpose of this study was to determine the protective effects of virgin coconut oil (VCO) treatment on hepatic oxidative stress and antioxidant defenses after maximum physical activity. Methods: This study used 24 healthy male rats. The rats were divided into four groups randomly consisted of six rats in each group. The control group (P0) was given 2 mL water, the treatment groups (VCO-1, VCO-2, and VCO-4) were given VCO 1 ml/200 g BW, 2 ml/200 g BW, and 4 ml/200 g BW, respectively, per day using gavage spuit. The rats were trained to swim for a month, 30 min/day in the 1st week, 35 min/day in the 2nd week, 40 min/ day in the 3rd week, and 45 min/day in the 4th week. After 28 days, the rats were forced to perform the maximal activity by putting the rats in water with no exit. Blood samples were collected immediately after the maximum physical activity, and then, all rats were killed and liver tissues were collected. The malondialdehyde (MDA), glutathione peroxidase (GPx), and serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvate transaminase level were then measured. Results: VCO increased swimming time to exhaustion, levels of GPx in the liver, which were accompanied by corresponding decreases in the MDA, alanine transaminase, and aspartate transaminase content. Conclusion: The results from this study indicate that VCO is effective in the prevention of oxidative stress following maximum physical activity.

Download Full-text

Differential Effects of Physical and Social Enriched Environment on Angiogenesis in Male Rats After Cerebral Ischemia/Reperfusion Injury

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.622911 ◽

2021 ◽

Vol 15 ◽

Author(s):

Xin Zhang ◽

Jing-Ying Liu ◽

Wei-Jing Liao ◽

Xiu-Ping Chen

Keyword(s):

Reperfusion Injury ◽

Functional Recovery ◽

Environmental Enrichment ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Artery Occlusion ◽

Male Rats ◽

Immunofluorescent Staining ◽

Housing Conditions ◽

Adhesive Removal

Different housing conditions, including housing space and the physiological and social environment, may affect rodent behavior. Here, we examined the effects of different housing conditions on post-stroke angiogenesis and functional recovery to clarify the ambiguity about environmental enrichment and its components. Male rats in the model groups underwent right middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO rats were divided into four groups: the physical enrichment (PE) group, the social enrichment (SE) group, the combined physical and social enrichment (PSE) group and the ischemia/reperfusion + standard conditioning (IS) group. The rats in the sham surgery (SS) group were housed under standard conditions. In a set of behavioral tests, including the modified Neurological Severity Score (mNSS), rotarod test, and adhesive removal test, we demonstrated that the animals in the enriched condition groups exhibited significantly improved neurological functions compared to those in the standard housing group. Smaller infarction volumes were observed in the animals of the PSE group by MRI detection. The enriched conditions increased the microvessel density (MVD) in the ischemic boundary zone, as revealed by CD31 immunofluorescent staining. The immunochemical and q-PCR results further showed that environmental enrichment increased the expression levels of angiogenic factors after ischemia/reperfusion injury. Our data suggest that all three enrichment conditions promoted enhanced angiogenesis and functional recovery after ischemia/reperfusion injury compared to the standard housing, while only exposure to the combination of both physical and social enrichment yielded optimal benefits.

Download Full-text