Tofacitinib enhances remyelination and improves myelin integrity in cuprizone-induced mice.

AIM: Demyelination and subsequent remyelination are well-known mechanisms in multiple sclerosis (MS) pathology. Current research mainly focused on preventing demyelination or regulating the peripheral immune system to protect further damage to the central nervous system. However, information about another essential mechanism, remyelination, and its balance of the immune response within the central nervous system's boundaries is still limited. MATERIALS AND METHODS: In this study, we tried to demonstrate the effect of the recently introduced Janus kinase (JAK)-signal transducer and activator of transcription (STAT) inhibitor, tofacitinib, on remyelination.Demyelination was induced by 6-week cuprizone administration, followed by 2-week tofacitinib (10, 30, and 100 mg/kg) treatment. RESULTS: At the functional level, tofacitinib improved cuprizone-induced decline in motor coordination and muscle strength, which were assessed by rotarod and hanging wire tests. Tofacitinib also showed anti-inflammatory effect by alleviating the cuprizone-induced increase in the central levels of interferon-γ (IFN-γ), interleukin (IL)-6, IL-1ß, and tumor necrosis alpha (TNF-α). Furthermore, tofacitinib also suppressed the cuprizone-induced increase in matrix metalloproteinases (MMP)-9 and MMP-2 levels. Additionally, cuprizone-induced loss of myelin integrity and myelin basic protein expression was inhibited by tofacitinib. At the molecular level, we also assessed phosphorylation of STAT-3 and STAT-5, and our data indicates tofacitinib suppressed cuprizone-induced phosphorylation in those proteins. CONCLUSION: Our study highlights JAK/STAT inhibition provides beneficial effects on remyelination via inhibition of inflammatory cascade.

Neuroprotective action of agmatine in rotenone-induced model of Parkinson's disease: Role of BDNF/cREB and ERK pathway.

Numerous studies have investigated the role of agmatine in the central nervous system and indicated neuroprotective properties. In addition to its potent antioxidant effects, agmatine is an endogenous neuromodulator and has wide spectrum molecular actions on different receptor subtypes (NMDA, Imidazoline 1-2, alpha-2 adrenoreceptor, 5-HT2a, 5-HT3) and cellular signaling pathways (MAPK, PKA, NO, BDNF). Although the neuroprotective effects of agmatine demonstrated in experimental Parkinson's disease model, the effects of agmatine with the aspect of neuroplasticity and possible signaling mechanisms behind agmatine actions have not been investigated. Herein, in this study, we investigated the role of the of agmatine on rotenone-induced Parkinson's disease model. Agmatine at the dose of 100 mg/kg i.p., was mitigated oxidative damage and alleviated motor impairments which were the results of the rotenone insult. Additionally, agmatine decreased neuronal loss, tyrosine hydroxylase immunoreactivity and increased cREB, BDNF and ERK1/2 expression in the striatum, which are crucial neuroplasticity elements of striatal integrity. Taken together, the present study expands the knowledge of molecular mechanisms behind neuroprotective actions of agmatine in Parkinson's disease, and as far as we have known, this is the first study to delineate agmatine treated activation of cellular pathways which are important elements in neuronal cell survival.

Effects of spermine and the passive avoidance learning (PAL) following cerebral ischemia in chicks: Association with neuroprotection of pyramidal cells.

The aim of this study is to investigate the effects of spermine and the passive avoidance learning on hippocampus following transient cerebral ischemia in the chicks. The study is composed of the pure control (CG), sham (SG) and experimental groups (n=20). Experimental groups (ischemia group, IG and ischemia-spermine group, ISG) were exposed to ischemia for 20min whereas the SG was exposed to sham operation and CG group was not exposed to any operation. Passive avoidance learning (PAL) was applied to the half number of the subjects in each group. Both before and after 7days from the ischemia, operated animals were taken to PAL and then they were sacrificed. Total numbers of neurons in the hippocampus were stereologically estimated using Cresyl violet stained sections. We detected that number of neurons was increased following PAL and especially spermine treatment. According to our results, we suggested that spermine may reduce the deleterious effects of the ischemia by causing to increase in the neuronal number and so, it may be slightly supportive to the PAL.

The influence of oral administration of rosuvastatin on calvarial bone healing in rats.

The purpose of this study is to investigate the potential of the systemic administration of different doses of rosuvastatin (RSV) on autogenous grafted critical-sized cortical bone defects. Twenty-four rats were divided into three groups: Group C (control), Group RSV-2 and Group RSV-5. A 5-mm diameter critical-size defect was created in the calvarium of each animal. In Group C, the defect was filled by autogenous graft only and rats were given saline solution with oral gavage for 28 days. In Group RSV-2 defects were filled with autogenous graft and rats were given 2 mg/kg rosuvastatin with oral gavage for 28 days. In Group RSV-5 defects were filled with autogenous graft and rats were given 5 mg/kg rosuvastatin with oral gavage for 28 days. All animals were euthanized at 28 days postoperative. Stereologic and micro-CT analyses were performed. New bone area (NBA) and connective tissue volumes were measured. Stereologic analysis showed that Group RSV-5 and RSV-2 had significantly more new bone at 4 weeks compared with group C. Connective tissue volumes were also significantly higher in RSV applicated groups. New bone and connective tissue volumes' difference were not statistically significant between RSV groups. Micro-CT results were similar with stereologic analyses. Orally administered RSV enhances bone regeneration in critical size calvarial rat defects filled with autogenous graft furthermore possible inflammatory effect should be investigated.

Controversies on electromagnetic field exposure and the nervous systems of children.

This paper reviewed possible health effects from exposure to low levels of electromagnetic field (EMF) in children, arising from electrical power sources and mobile phones. Overall, the information about effects on developmental processes and cognitive functions is insufficient and further research on children and adolescents is critically needed. New research approaches are required focused on the effects on the developmental processes of children exposed to electromagnetic fields, using consistent protocols. When the current data were considered in detail, it was noted that children's unique vulnerabilities make them more sensitive to EMFs emitted by electronics and wireless devices, as compared to adults. Some experimental research shows a neurological impact and exposure in humans may lead to the cognitive and behavioral impairments. Because of the proliferation of wireless devices, public awareness of these dangers now is important to safeguard children's future healthy brain development.

Effects of melatonin on diclofenac sodium treated rat kidney: a stereological and histopathological study.

OBJECTIVE: In this study, we aimed to investigate the effect of diclofenac sodium (DS) and melatonin (MEL) on kidney of the prenatally administered rats. MATERIALS AND METHODS: Pregnant rats were divided into the control, physiological saline, DS, and DS + MEL groups. All injections were given beginning from the 5th day after mating to the 15th day of the pregnancy. Physical dissector and Cavalieri principle were used to estimate the numerical density and total number of glomeruli and the volumetric parameters of kidney, respectively. RESULTS: Our stereological results indicated that DS application during the pregnancy lead to decrease in the mean volume, numerical density, and total number of the glomeruli (p < 0.05). In addition, we determined that usage of the MEL with the DS caused increases in the mean volume, numerical density, and total number of the glomeruli (p < 0.05). So, there was no significant difference in terms of the any parameter between the CONT and DS + MEL groups (p > 0.05). Light microscopic investigation showed congestion in blood vessels and shrinkage of the Bowman's space in the DS group. Moreover, there was degeneration in nephrons including glomerulosclerosis and tubular defects, and an increase in the connective tissue in the kidneys of the DS-treated group. However, usage of the MEL with the DS caused preventing of these pathological alterations in the kidney. DISCUSSION: We suggested that DS might lead to adverse effects in the kidneys of the rats that are prenatally subjected to this drug. Fortunately, these adverse effects can be prevented by the melatonin supplementation.