Neuroprotective Role of Selenium Nanoparticles Against Behavioral, Neurobiochemical and Histological Alterations in Rats Subjected to Chronic Restraint Stress.

Chronic stress induces changes in the prefrontal cortex and hippocampus. Selenium nanoparticles (SeNPs) showed promising results in several neurological animal models. The implementation of SeNPs in chronic restraint stress (CRS) remains to be elucidated. This study was done to determine the possible protective effects of selenium nanoparticles on behavioral changes and brain oxidative stress markers in a rat model of CRS. 50 rats were divided into three groups; control group (n = 10), untreated CRS group (n = 10) and CRS-SeNPs treated group (n = 30). Restraint stress was performed 6 h./day for 21 days. Rats of CRS-SeNPs treated group received 1, 2.5 or 5 mg/kg SeNPs (10 rats each) by oral gavage for 21 days. Rats were subjected to behavioral assessments and then sacrificed for biochemical and histological analysis of the prefrontal cortex and hippocampus. Prefrontal cortical and hippocampal serotonin levels, oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx), tumor necrosis factor alpha (TNF-α) and caspase-3 were assessed. Accordingly, different doses of SeNPs showed variable effectiveness in ameliorating disease parameters, with 2.5 mg/kg dose of SeNPs showing the best improving results in all studied parameters. The present study exhibited the neuroprotective role of SeNPs in rats subjected to CRS and proposed their antioxidant, anti-inflammatory and anti-apoptotic effects as the possible mechanism for increased prefrontal cortical and hippocampal serotonin level, ameliorated anxiety-like and depressive-like behaviors and improved prefrontal cortical and hippocampal histological architecture.

The Therapeutic Potential of Amniotic Fluid-Derived Stem Cells on Busulfan-Induced Azoospermia in Adult Rats.

BACKGROUND: Busulfan is an alkylating chemotherapeutic agent that is routinely prescribed for leukemic patients to induce myelo-ablation. However, it also results in azoospermia and infertility in cancer survivors. This research was constructed to explore the possible therapeutic role of amniotic fluid-derived stem cells (AFSCs) in improving busulfan-induced azoospermia in adult rats. METHODS: Forty two adult male albino rats were randomized into: (1) control group, (2) azoospermia group, (3) spontaneous recovery group, and (4) AFSCs-treated group, in which AFSCs were transplanted through their injection into the testicular efferent ducts. The assessment included a histo-pathological examination of the seminiferous tubules by the light and transmission electron microscopes. Additionally, the confocal laser scanning microscope was used for confirmation of homing of the implanted cells. Moreover, we conducted an immuno-fluorescence study for detection of the proliferating cell nuclear antigen (PCNA) in the spermatogenic cells, epididymal sperm count, and a histo-morphometric study. RESULTS: AFSCs successfully homed over the basement membrane of the injured seminiferous tubules. They greatly attenuated busulfan-induced degenerative and oxidative changes. They also caused a re-expression of PCNA in the germ cells, leading to resumption of spermatogenesis and re-appearance of spermatozoa. CONCLUSION: AFSCs could be a promising treatment modality for male infertility induced by chemotherapy, as they possess prominent regenerative, anti-apoptotic, and anti-inflammatory potentials.

Downstream modulation of extrinsic apoptotic pathway in streptozotocin-induced Alzheimer's dementia in rats: Erythropoietin versus curcumin.

Erythropoietin and curcumin showed promising neuroprotective effects in various models of Alzheimer's dementia. This study was designed to compare the beneficial effects of erythropoietin and/or curcumin in intracerebro-ventricular (ICV) streptozotocin-induced Alzheimer's like disease in rats. Rats received ICV injection of either saline (control, n=8 rats), or streptozotocin. Three weeks following surgery, streptozotocin-injected rats were assigned into 4 groups (8 rats each); vehicle, curcumin (80mg/kg/day, orally), erythropoietin (500 IU/kg every other day, intraperitoneally) and combined (curcumin and erythropoietin)-treated groups. After 3 months of treatment, rats were subjected to neurobehavioral testing, and then killed for biochemical and histological assessment of hippocampus. Fas ligand protein and caspase-8 activity as mediators of extrinsic apoptotic pathway, oxidative stress markers (malondialdehyde and reduced glutathione) and ß-amyloid (1-40 and 1-42) peptides were measured. The results showed that administration of erythropoietin suppressed extrinsic apoptosis better than curcumin, while curcumin was more effective in combating oxidative stress in ICV-streptozotocin injected rats. Both erythropoietin and curcumin treatments (individually or combined) equally reduced the hippocampal ß-amyloid accumulation and improved cognitive impairment in Morris water maze and passive avoidance tasks. The combined treatment was the most effective in ameliorating apoptosis and oxidative stress rather than behavioral responses or ß-amyloid burden. In conclusion, ICV-streptozotocin-induced Alzheimer's dementia activates hippocampal Fas ligand-mediated apoptosis, which could be reduced by erythropoietin and/or curcumin treatment. Curcumin supplementation alone could ameliorate cognitive deficits and reverse biochemical alterations in ICV-streptozotocin Alzheimer's rat model without the hazardous polycythemic effect of long-term erythropoietin injection.