Hyperthermia alters neurobehavior by affecting cell proliferation and neuronal survival in young male rats.

Maintenance of body temperature within physiological range is critical for the fetal and neonatal development. Hyperthermia is one of the most frequently encountered pediatric complaints and may cause neurological disorders due to neuronal injury. In this study, we aimed to investigate the effects of hyperthermia on behavioral alterations, neuronal survival, apoptosis, and cell proliferation in young male Sprague-Dawley rats. Twenty-one 13-day-old rats were randomly divided into three groups (n = 7 per group). Body temperature was increased to 39°C and 41°C in a hyperthermia induction chamber for 30 min, whereas the animals in control group were maintained at 36°C. Twenty-four hours after hyperthermia, animals were subjected to the open field test, elevated-O-maze test, and grip strength test to assess the locomotor activity, anxiety, and motor function. Neuronal survival, apoptosis, and cell proliferation were investigated in cortex, hippocampal dentate gyrus (DG) and CA1 regions, and corpus callosum (CC). Decreased locomotor activity and motor function and increased anxiety were observed in the hyperthermia groups, and these were more pronounced in the 41°C group. Neuronal survival was significantly decreased in DG, CA1, and CC in the hyperthermia groups (**p < 0.01). Apoptosis was significantly induced in cortex, DG, and CC of the animals exposed to heat (*p < 0.05). In addition, cell proliferation positivity decreased significantly only in DG and CC of the animals exposed to heat (*p < 0.05). Our results suggest that neurobehavioral deficits caused by hyperthermia may be due to the increased apoptosis and neuronal cell death and decreased cell proliferation in the brain of postnatal developing rats.

Increased Colostral Concentration of Macrophage Migration Inhibitory Factor in Mothers with Premature Rupture of Membranes.

Objective: The colostrum contains macrophage migration inhibitory factor (MIF), which plays an important role in protecting newborns from infections. As such, colostrum may be specifically important to prevent early onset neonatal sepsis among neonates born after premature rupture of membranes (PROM). However, the effect of PROM on the colostral MIF concentration has not been previously described. The aim of this study is to compare the concentration of MIF in the colostrum of mothers with and without PROM. Methods: The study group consisted of 44 women, 22 of whom had PROM. Colostrum was expressed and collected within 72 hours of birth. MIF concentration was measured using the enzyme-linked immunosorbent assay method and compared between mothers with and without PROM. Results: There were no differences between the two groups (PROM group n = 22, control group n = 22) with regard to the age of mothers, mode of delivery, neonatal gestational age, birth weight, and sex of the infants (p > 0.05). The colostral MIF concentration was significantly higher among mothers with than without PROM (p = 0.0001). There was a positive and significant correlation between the colostral MIF concentration and PROM duration (r = 0.314, p = 0.038). Conclusions: PROM was associated with a higher colostral MIF concentration, with this concentration being positively correlated with the duration of PROM. This increased concentration may be important in offering these neonates additional protection against early onset infections, which is a risk associated with PROM.

Thymoquinone administration ameliorates Alzheimer's disease-like phenotype by promoting cell survival in the hippocampus of amyloid beta1-42 infused rat model.

BACKGROUND: Thymoquinone (TQ), a biologically active ingredient of Nigella sativa, has anti-inflammatory, anti-oxidative and neuroprotective properties. Therefore, it could be a good candidate in the recovery of Alzheimer`s disease (AD) pathology rather than current symptomatic reliefs. PURPOSE: In the present study, we examined the molecular healing effects of TQ in amyloid beta 1-42 (Aß1-42) peptide-infused AD rat hippocampus. STUDY DESIGN: A micro-osmotic pump containing aggregated Aß1-42 was cannulated into the hippocampus of adult female rats. After two weeks infusion, the dose of TQ (10 mg/kg or 20 mg/kg) was determined according to the HPLC results of cerebrospinal fluid and TQ was given to rats intragastrically for 15 days. METHODS: The memory performance of rats was determined by Morris water maze test. Afterwards, the acetylcholinesterase (AChE) level were measured by ELISA. Histopathological examinations of hippocampal tissue were performed for cell survival by Nissl staining, for detection of amyloid plaque deposits by Congo red staining and for determination of degenerating neurons by Fluoro Jade C staining. MicroRNA/mRNA levels and protein expressions of AD-related genes and proteins were analyzed by Real-Time Polymerase Chain Reaction and Western Blotting, respectively. RESULTS: Administration of TQ enhanced the memory performance of Aß1-42 infused rats and it also ameliorated the neuronal loss in the cornu ammonis (CA1), but not in the dentate gyrus (DG). In addition, TQ treatment decreased the fibril deposition whose accumulation was significantly higher in the Aß1-42-infused animals compared to that of the control group. The expression profiles of mir29c and Bax which significantly upregulated in the Aß1-42-infused animals were attenuated by TQ. Furthermore, administration of TQ decreased the expressions of Aß, phosphorylated-tau, and BACE-1 proteins. There was no significant therapeutic effect of TQ on the AKT/GSK3ß or MAPK signaling pathways which were affected due to Aß1-42 infusion. CONCLUSION: TQ has the capacity to recover the neuropathology by removing Aß plaques and by restoring neuron viability. All might have established the molecular basement of the consolidation in the memory observed by means of TQ treatment.

Parathyroid Allotransplant for Persistent Hypocalcaemia: A New Technique Involving Short-Term Culture.

OBJECTIVES: To develop a new parathyroid allotransplant method for the treatment of permanent hypoparathyroidism. MATERIALS AND METHODS: Parathyroid cells 50 × 10(6) derived from a parathyroid hyperplasia patient were transferred to a 61-year-old patient who had thyroidectomy 17 years earlier, allowing to papillary thyroid cancer; he was admitted to our outpatient clinic with symptomatic chronic hypocalcemia. Cell isolation, cryopreservation, and culturing were conducted according to a new protocol. RESULTS: During a follow-up of 5 months, the patient had no complications that could indicate rejection, and clinical symptoms completely resolved without requiring any drug supplementation. CONCLUSIONS: Here, we report a new method, enabling fast and cost-effective parathyroid allotransplant with maintained tissue viability sufficient to treat persistent hypocalcemia.

Intravenous TAT-GDNF is protective after focal cerebral ischemia in mice.

BACKGROUND AND PURPOSE: Delivery of therapeutic proteins into tissues and across the blood-brain barrier is severely limited by their size and biochemical properties. The 11-amino acid human immunodeficiency virus TAT protein transduction domain is able to cross cell membranes and the blood-brain barrier, even when coupled with larger peptides. The present studies were done to evaluate whether TAT-glial line-derived neurotrophic factor (GDNF) fusion protein is protective in focal cerebral ischemia. METHODS: Anesthetized male C57BL/6j mice were submitted to intraluminal thread occlusion of the middle cerebral artery. Reperfusion was initiated 30 minutes later by thread retraction. Laser Doppler flow was monitored during the experiments. TAT-GDNF, TAT-GFP (0.6 nmol each), or vehicle was intravenously applied over 10 minutes immediately after reperfusion. After 3 days (30 minutes of ischemia), animals were reanesthetized and decapitated. Brain injury was evaluated by histochemical stainings. RESULTS: Immunocytochemical experiments confirmed the presence of TAT-GDNF protein in the brains of fusion protein-treated nonischemic control animals 3 to 4 hours after TAT fusion protein delivery. TAT-GDNF significantly reduced the number of caspase-3-immunoreactive and DNA-fragmented cells and increased the number of viable neurons in the striatum, where disseminated tissue injury was observed, compared with TAT-GFP- or vehicle-treated animals. CONCLUSIONS: Our results demonstrate that TAT fusion proteins are powerful tools for the treatment of focal ischemia when delivered both before and after an ischemic insult. This approach may be of clinical interest because such fusion proteins can be intravenously applied and reach the ischemic brain regions. This approach may therefore offer new perspectives for future strategies in stroke therapy.