Caffeic Acid Phenethyl Ester With Mesenchymal Stem Cells Improves Behavioral and Histopathological Changes in the Rat Model of Parkinson Disease.

Introduction: Parkinson disease (PD) results from the destruction of dopaminergic neurons in the brain. This study aimed to investigate the protective effects of natural antioxidants such as caffeic acid phenethyl ester (CAPE) to maintain these neurons. Methods: CAPE is one of the main ingredients of propolis. Intranasal administration of 1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine (MPTP) was used to generate a PD model in rats. A total of 2×bone marrow stem cells (BMSCs) were injected from the tail vein. Behavioral tests, immunohistochemistry, DiI, cresyl fast violet, and TUNEL staining were used to evaluate the rats 2 weeks after treatment. Results: In all treatment groups with stem cells, the DiI staining method revealed that the cells migrated to the substantia nigra pars compacta after injection. Treatment with CAPE significantly protects dopaminergic neurons from MPTP. The highest number of tyrosine hydroxylase (TH) positive neurons was seen in the pre-CAPE+PD+stem cell (administration of CAPE, then the creation of PD, finally injection of stem cells) group. The number of TH+cells in all groups that received CAPE was significant compared to groups that received the stem cells only (P<0.001). Intranasal administration of MPTP significantly increases the number of apoptotic cells. The lowest number of apoptotic cells was in the CAPE+PD+stem cell group. Conclusion: The results showed that the use of CAPE and stem cells in Parkinson rats caused a significant reduction in the apoptotic cells.

The effect of pyridostigmine on post-stroke dysphagia: A randomized clinical trial.

Background: Swallowing is one of the most complex functions of the central nervous system (CNS), which is controlled by different parts of the brain. Oropharyngeal dysphagia (OD) is one of the most common complications after stroke. Despite a variety of behavioral, compensatory, and rehabilitative methods, many stroke patients still suffer from swallowing disorders that adversely affect their quality of life (QOL). The aim of this study was to evaluate the effect of pyridostigmine on patients with post-stroke dysphagia. Methods: A randomized, double-blind, placebo-controlled clinical trial was carried out on 40 patients suffering from post-stroke dysphagia. Patients were assigned randomly into two groups: intervention and control groups (20 in each group). The intervention group was treated with pyridostigmine (60 mg, three times a day, 30 minutes before each meal for three weeks), and the control group received placebo treatment in the same way. All patients (intervention and control) were evaluated according to National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Functional Communication Measures (FCM)/American Speech-Language-Hearing Association (ASHA) criteria at baseline and after three weeks of intervention. Values of P < 0.05 were considered statistically significant. Results: In the intervention group, the mean values of NIHSS, mRS, and ASHA/FCM were significantly reduced following three weeks of treatment with pyridostigmine (P = 0.002, P = 0.003, and P < 0.001, respectively), but no significant differences were found in the mean NIHSS, mRS, and ASHA/FCM in the placebo group. Conclusion: Although pyridogestamine is somewhat effective in post-stroke dysphagia, it has not been shown to be more important in preventing aspiration pneumonia and length of hospital stay.

Nanomicellar curcuminoids attenuates renal ischemia/reperfusion injury in rat through prevention of apoptosis and downregulation of MAPKs pathways.

Renal ischemia/reperfusion (I/R) injury is considered as a main problem in clinical practice. Curcuminoids, the active constituents of turmeric, seem to have potential renoprotective effects. However, the poor bioavailability of curcuminoids restricts their therapeutic effects. In the present study, the effect of nanomicellar curcuminoids (NC) treatment on renal function, histology, total antioxidant capacity (TAC), total oxidative stress (TOS), caspase-3 level as well as mitogen activated protein kinases (MAPKs: JNK, p38 and ERK) phosphorylation were evaluated following renal I/R. Adult male Sprague-Dawley rats were administered NC at the dose of 25 mg/kg 1 h before renal ischemia induction. The animals were subjected to bilateral renal ischemia for 60 min and reperfusion for 24 h. Subsequently, blood urea nitrogen (BUN), creatinine (Cr), renal histopathology, TAC, TOS, and oxidative stress index, cleaved caspase-3 level, Bax and MAPKs signaling were evaluated. The results indicated that NC pretreatment at the dose of 25 mg/kg significantly improved renal function as well as histolopatholgical damages. Moreover, NC reduced the level of renal oxidative stress, cleaved caspase-3 and Bax (as the proapoptotic proteins) and suppressed the activated Jun N-terminal Kinase (JNK), p38 and extracellular receptor kinase (ERK) signaling induced by renal I/R. The findings of the current study indicate that NC might prevent the injury induced by renal I/R through suppression of oxidative stress, apoptosis and MAPKs pathways.

Irisin protects the substantia nigra dopaminergic neurons in the rat model of Parkinson's disease.

OBJECTIVES: Exercise ameliorates the quality of life and reduces the risk of neurological derangements such as Alzheimer's (AD) and Parkinson's disease (PD). Irisin is a product of the physical activity and is a circulating hormone that regulates the energy metabolism in the body. In the nervous system, Irisin influences neurogenesis and neural differentiation in mice. We previously demonstrated that co-treatment of bone marrow stem cells (BMSCs) with a neurotrophic factor reduce Parkinson's symptoms. Our goal in this project was to evaluate whether Irisin with BMSCs can protect the dopaminergic (DA) neurons in PD. MATERIALS AND METHODS: 35 adult male Wistar rat weighing (200-250 g) were chosen. They were separated into five experimental groups (n=7). To create a Parkinson's model, intranasal (IN) administration of the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used. The BMSCs (2×106) and Irisin (50 nm/ml) was used for 7 days for treatment after creation of the PD model. After completion of the tests (4 weeks), their brains were used for the TUNEL and immunohistochemical (IHC) assays. RESULTS: One of the important results of this study was that the Irisin induce BMSCs transport into the injured area of the brain. Co-treatment of the Irisin with BMSCs increased tyrosine hydroxylase-positive neurons (TH+) in substantia nigra (SN) and striatum of the PD mice brain. In this group, the number of TUNEL-positive cells significantly decreased. Behavioral symptoms were better in the combination group and Irisin simultaneously. CONCLUSION: Co- treatment of Irisin with BMSCs protects the DA neurons from degeneration and apoptotic process after MPTP injection.