Caffeine prevents bilirubin-induced cytotoxicity in cultured newborn rat astrocytes.

OBJECTIVE: Unconjugated bilirubin (UCB) may cause neurotoxicity in preterm neonates due to immaturity of UGT1A1 leading to bilirubin accumulation in the brain. Caffeine used in the treatment of apnea of prematurity was reported to decrease mechanical ventilation requirement, the frequencies of bronchopulmonary dysplasia, patent ductus arteriosus, cerebral palsy and neurodevelopmental disorders in very low birth weight infants. However, the effect of caffeine on hyperbilirubinemia was not yet clarified. METHODS: We used astrocyte cell cultures obtained from 2-day-old Wistar albino rats via modified Cole and de Vellis method. UCB concentration toxic to 50% of astrocytes, and caffeine concentration increasing cell viability 100% were used in experiments. While no medication was applied to the control group, UCB (50 µM) and caffeine (100 µM) were applied to the bilirubin and caffeine groups for 24 h. Prophylactic and therapeutic caffeine groups were treated with caffeine 4 h before and after UCB exposure. The effects of caffeine were investigated in rat astrocytes exposed to UCB in terms of cell viability, apoptosis, antioxidant defense, proinflammatory cytokines, and Toll-like receptor (TLR)s. RESULTS: Compared to the control group, UCB increased apoptosis, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, total nitrate/nitrite, and TLR4 levels, and decreased cell viability, catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, glutathione, and TLR9 levels (for all p < .001). Conversely, prophylactic and therapeutic caffeine improved the detrimental effects of UCB. CONCLUSIONS: Caffeine seems encouraging for the prevention and treatment of bilirubin neurotoxicity in rats by means of its antiapoptotic, antioxidant, anti-inflammatory, anti-nitrosative, and anti-TLR-4 properties.

Relationship of age with the size of the interventricular foramina and aqueductus sylvii: a morphometric evaluation.

OBJECTIVES: The ventricular system is an essential part of the brain. Various pathologies directly or indirectly affect the size of this system. Morphometric analysis of the cerebral ventricular system is important for evaluating changes due to growth, aging, and intrinsic and extrinsic pathologies. The aim of this study was to evaluate the normative data for the interventricular foramina and cerebral aqueduct with regard to surgery and clinical situations. METHODS: Cranial magnetic resonance imaging (MRI) scans of 128 healthy subjects (63 female subjects, 65 male subjects; 2-63 years old) were individually reviewed. The right and left interventricular foramina lengths and diameters and the cerebral aqueduct length and diameter were statistically evaluated and compared between sexes and among age groups. RESULTS: There were no significant differences among the age groups in either sex (P > 0·05). Additionally, there was no correlation between age and measurement parameters (P > 0·05). DISCUSSION: We did not observe any changes in interventricular foramina or cerebral aqueduct measurements in healthy subjects from a wide range of age groups. Such changes should be useful for diagnosing diseases that affect the ventricular system and planning surgical procedures, especially those involving the ventricular system.

Effect of testosterone propionate on hippocampal pyramidal neuron number in female rats.

INTRODUCTION: The hippocampus is an important region of the brain that regulates cognitive and emotional functions. In this study, we examined the impact of perinatal administration of testosterone propionate (TP) on the number of pyramidal neurons in the CA1 and CA3 regions of the hippocampi of female rats. METHODS: Five groups of rats were used in this study. Three groups of female rats were administered TP in either both the prenatal and the postnatal periods (Group 1), only the prenatal period (Group 2) or only the postnatal period (Group 3). The other two groups of rats included control females (Group 4) and control males (Group 5). The rats were sacrificed on postnatal Day 120 and their brains were analysed for hippocampal pyramidal neuron number using stereological methods. RESULTS: Control male rats (Group 5; p = 0.043) and TP-treated female rats in Groups 1 (p = 0.012) and 2 (p = 0.037), but not Group 3 (p > 0.05), had a significantly higher number of pyramidal neurons than control female rats (Group 4). The rats in Group 1 had the highest number of pyramidal neurons among the female rats. CONCLUSION: Perinatal TP treatment has an augmenting effect on the number of pyramidal neurons in the hippocampi of female rats. We also found gender-based differences in the hippocampi of male and female rats, with a higher number of pyramidal neurons seen in male rats. Continuous TP administration during the prenatal and postnatal periods is more effective than administration only in the prenatal or postnatal period.

Injection of specific amyloid-beta oligomers (beta1₋40:beta1₋42 = 10:1) into rat medial septum impairs memory retention without inducing hippocampal apoptosis.

OBJECTIVES: Because of the well-known neurochemical interactions between the septum and hippocampus during memory processes, we investigated the effect of amyloid-beta (A-beta) injection into the medial septum (MS) on the behavior in Wistar rats. We also assessed whether the observed effects were functional or due to apoptosis. METHODS: Specific A-beta oligomers (beta1-40:beta1-42 = 10:1) were injected into MS for seven consecutive days. Behavior was assessed with the Morris water maze task. RESULTS: Compared with the control group, rats that received A-beta oligomers exhibited significant memory retention impairment (P < 0·05) without apoptosis in the cornu ammonis (CA)1 and CA3 regions of the dorsal hippocampus. DISCUSSION: These data indicate that septal injection of A-beta impairs memory retention, even in the absence of hippocampal apoptosis. This result might bring new insight to spatial memory-related disorders like Alzheimer's disease (AD).

Protective effect of insulin and glucose at different concentrations on penicillin-induced astrocyte death on the primer astroglial cell line.

Astrocytes perform many functions in the brain and spinal cord. Glucose metabolism is important for astroglial cells and astrocytes are the only cells with insulin receptors in the brain. The common antibiotic penicillin is also a chemical agent that causes degenerative effect on neuronal cell. The aim of this study is to show the effect of insulin and glucose at different concentrations on the astrocyte death induced by penicillin on primer astroglial cell line. It is well known that intracranial penicillin treatment causes neuronal cell death and it is used for experimental epilepsy model commonly. Previous studies showed that insulin and glucose might protect neuronal cell in case of proper concentrations. But, the present study is about the effect of insulin and glucose against astrocyte death induced by penicillin. For this purpose, newborn rat brain was extracted and then mechanically dissociated to astroglial cell suspension and finally grown in culture medium. Clutters were maintained for 2 weeks prior to being used in these experiments. Different concentrations of insulin (0, 1, 3 nM) and glucose (0, 3, 30 mM) were used in media without penicillin and with 2 500 µM penicillin. Penicillin decreased the viability of astroglial cell seriously. The highest cell viability appeared in medium with 3 nM insulin and 3 mM glucose but without penicillin. However, in medium with penicillin, the best cell survival was in medium with 1 nM insulin but without glucose. We concluded that insulin and glucose show protective effects on the damage induced by penicillin to primer astroglial cell line. Interestingly, cell survival depends on concentrations of insulin and glucose strongly. The results of this study will help to explain cerebrovascular pathologies parallel to insulin and glucose conditions of patient after intracranial injuries.

Hippocampal neuron number loss in rats exposed to ingested sulfite.

Sulfite, which is continuously formed in the body during metabolism of sulfur-containing amino acids, is commonly used in preservatives. It has been shown that there are toxic effects of sulfite on many cellular components. The aim of this study was to investigate the possible toxic effects of sulfite on pyramidal neurons by counting cell numbers in CA1 and CA2-CA3 subdivisions of the rat hippocampus. For this purpose, male albino rats were divided into a control group and a sulfite group (25 mg/kg). Sulfite was administered to the animals via drinking water for 8 weeks. At the end of the experimental period, brains were removed and neurons were estimated in total and in a known fraction of CA1 and CA2-CA3 subdivisions of the left hippocampus by using the optical fractionator method--a stereological method. Results showed that sulfite treatment caused a significant decrease in the total number of pyramidal neurons in three subdivisions of the hippocampus (CA1 and CA2-CA3) in the sulfite group compared with the control group (p < 0.05, Mann Whitney U test). It was concluded that exogenous administration of sulfite causes loss of pyramidal neurons in CA1 and CA2-CA3 subdivisions of the rat hippocampus.

Describing normal variations of head and face by using standard measurement and craniofacial variability index (CVI) in seven-year-old normal children.

To define the line separating normal from abnormal craniofacial appearance is complex and difficult because there are many craniofacial measurement parameters, and there are also many factors that influence the craniofacial morphology, such as genetics and environmental influence. The aim of this study is to define the range of normal distribution of craniofacial morphology by using different numerical methods in seven-year-old students in Denizli, Turkey. For this purpose, height, weight and 20 defined craniofacial parameters (including face height, face width, face depth, eyes, nose, ear, mouth and head) of 61 female and 58 male (119 total) normal cases were measured. Every measurement was taken twice by the same investigator and the standard anthropometric methods of measurements were used. All data were recorded by computer and analyzed statistically. At the end, craniofacial variability index (CVI) was found 0.874 +/- 0.338 in female, 0.824 +/- 0.333 in male. Furthermore, the female results were compared to the male results. Parameters were correlated with each other. Seven years old is the beginning age for primary school in Turkey. So, it is an important year for initial diagnostic screening in children with facial syndromes, and it is also important for pre-and postsurgical assessments of children with craniofacial anomalies.