RESUMEN
Introduction: Stem cell therapy is a highly promising strategy in various degenerative diseases. Intranasal administration of stem cells could be considered as a non-invasive treatment option. However, there is great debate concerning the ability of stem cells to reach distant organs. It is also unclear in such a case if they can alleviate age-related structural changes in these organs. Aim: The aim of this study is to evaluate the ability of intranasal administration of adipose-derived stem cells (ADSCs) to reach distant organs of rats at different time intervals and to investigate their effects on age-related structural changes in these organs. Materials and Methods: Forty-nine female Wistar rats were used in this study, seven of which were adults (6-month-old) and 42 were aged (2-year-old). Rats were divided into three-groups: Group-I (adult control), Group-II (aged), and Group-III (aged ADSCs treated). Rats of Groups I and II were sacrificed after 15 days from the beginning of the experiment. Rats of Group III were treated with intranasal ADSCs and were sacrificed after 2-h, 1-day, 3-day, 5-day, and 15-day. Heart, liver, kidney, and spleen specimens were collected and processed for H and E, CD105 immunohistochemistry, and immunofluorescent techniques. Morphometric study and statistical analysis were performed. Results: ADSCs appeared in all organs examined after 2-h of intranasal administration. Their maximum presence was detected after 3-day of administration, after which their immunofluorescence gradually decreased and nearly disappeared from these organs by the 15th day. Improvement of some age-related deterioration in the structure of the kidney and liver occurred at day 5 after intranasal administration. Conclusions: ADSCs effectively reached the heart, liver, kidney, and spleen after intranasal administration. ADSCs ameliorated some age-related changes in these organs.
RESUMEN
Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.