Transplantation of bone marrow-derived mesenchymal stem cells ameliorated dopamine system impairment in a D-galactose-induced brain ageing in rats.

BACKGROUND: Ageing is the primary risk factor for Parkinson's disease. Progressive motor and coordination decline that occurs with ageing has been linked to nigrostriatal dysfunction. Few studies have investigated the efficacy of mesenchymal stem cells in ameliorating the structural and functional alterations in the ageing nigrostriatal system. This study is the first to evaluate the effects of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose- induced rat model of nigrostriatal ageing. MATERIALS AND METHODS: BMMSCs were intravenously injected once every 2 weeks for 8 weeks. The transplanted cells survived, migrated to the brain, and differentiated into dopaminergic neurones and astrocytes. RESULTS: BMMSC transplantation improved locomotor activity, restored dopaminergic system function, preserved atrophic dopaminergic neurones in the substantia nigra, exerted antioxidative effects, and restored neurotrophic factors. CONCLUSIONS: Our findings demonstrate the efficacy of BMMSC injection in a nigrostriatal ageing rat model, and suggest that these cells may provide an effective therapeutic approach for the ageing nigrostriatal system.

Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats.

BACKGROUND: Aging is a complex process accompanied by numerous morphological, functional, and metabolic impairments in the brain, and a critical risk factor involved in the increasing incidence of neurodegenerative diseases. Few studies have evaluated the efficacy of different sources of mesenchymal stem cells (MSCs) in ameliorating the early morphological and functional alterations in the aging brain. This study, for the first time, evaluated the potential efficacy of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of brain aging. MATERIALS AND METHODS: BMMSCs (1 × 106) were intravenously injected into brain aging model rats once every 2 weeks for 8 weeks. RESULTS: The transplanted cells survived and migrated to the brain, and differentiated into astrocytes and neurons, including choline acetyltransferase neurons. BMMSC transplantation improved locomotor activity and cognitive functions, restored cholinergic system function, protected atrophic cholinergic neurons in the basal forebrain, induced antioxidative effects and restored neurotrophic factors, and modulated hippocampal synaptic plasticity by upregulating PSD95 and Egr1 expression. CONCLUSIONS: Our findings demonstrated the efficacy of BMMSC injection in an aging rat model and suggest that these cells may be developed into an effective cell therapy for the aging brain.

Quercetin protects against experimentally-induced myocardial infarction in rats by an antioxidant potential and concomitant activation of signal transducer and activator of transcription 3.

This study tested if the protective effect of quercetin (QUR) against experimentally-induced acute myocardial infarction (AMI) in rats involves modulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. Rats were divided into 6 groups as sham-operated (control), control + QUR, AMI, AMI + QUR, AMI + S3I-210 (a STAT3 inhibitor), and AMI + QUR + S31-201. QUR (50 mg/kg/orally) and S3I-201 (a STAT3 inhibitor) (5 mg/kg/i.p.) were administered for 7 days before the induction of AMI and the experiment was ended 24 h post-AMI. Pre-treatment with QUR reduced the infarct size, improved the left ventricular (LV) functions and the structure of the myofibrils and the mitochondria, and reduced circulatory levels of lactate dehydrogenase (LDH), creatinine-kinase MB (CKMB), and troponin-I. QUR also reduced LV levels of reactive oxygen species (ROS) and malondialdehyde (MDA), inhibited the opening of the mitochondria transition pores (mtPTP), and reduced protein levels of cytochrome-C, cleaved caspase-3 and p-JAK2 (Tyr1007/1008) in the LVs of AMI rats. In the LV of both the control and AMI rats, QUR didn't affect the levels of p-JAK2 but significantly increased the levels of total glutathione (GSH) and manganese superoxide dismutase (MnSOD), reduced the levels of Bax and the nuclear levels and activity of NF-κB p65, tumor necrosis-factors-α (TNF-α), interleukin-6 (IL-6), and p-STAT1 (Ser727) but further increased the levels of p-STAT3 (Ser727). All these effects exerted by QUR were partially reversed but the decrease in nuclear protein levels and activity of NFκB, levels of TNF-α and IL-6, and pSTAT3 were completely prevented by co-administration of S3I-201. In conclusion, QUR protects against MI by upregulation of antioxidants and activation of STAT3.

Vitamin C attenuates the toxic effect of nutmeg on primary visual occipital cortex in rats.

BACKGROUND: Nutmeg is neurotoxic in rats and possibly neurotoxic also in hu- mans. The aim of this study is to investigate the effect of nutmeg on the primary visual occipital cortex of adult male rat and to evaluate the possible protective role of vitamin C. MATERIALS AND METHODS: Fifty Sprague-Dawley adults male rats were randomly divided into three main groups; control, nutmeg-treated (500 and 1000 mg/kg/ /day) and protected groups (nutmeg + vitamin C [500 mg/kg/day]). All rats were treated orally by gavage for 5 days per week for 6 weeks. At the end of the experiment, primary visual occipital cerebral cortex was subjected to histological, immunohistochemical and genetic analyses. RESULTS: Our results revealed toxic effects of nutmeg on the primary visual occipital cerebral cortex in adult male albino rat. This was indicated by histopathological alterations, including pyknotic nuclei surrounded with vacuolations by light micro- scopic studies and degenerations of organelles by electron microscopic studies. In addition, we detected an increase in immunoreactivity for GFAP and caspase-3 by immunohistochemical assessments. Apoptotic bands appeared in genetic studies. Co-administration of vitamin C ameliorated nutmeg-induced toxic alterations on the primary visual occipital cerebral cortex. CONCLUSIONS: Nutmeg administration caused histopathological and genetic changes in the primary visual occipital cerebral cortex in adult male albino rats. These changes were improved by co-administration of vitamin C.