Periventricular leukomalacia (PVL), a common neonatal brain white matter (WM) lesion, is frequently associated with cerebral palsy. Growing evidence has indicated that in addition to ischemia/reperfusion injury, cytokine-induced brain injury associated with maternal or fetal infection may also play an important role in the pathogenesis of PVL. Recent studies have shown that administration of lipopolysaccharide (LPS) to pregnant rats causes enhanced expression of the cytokines, i.e., IL-1β, TNF-α, and IL-6, in fetal brains. In recent years, it has been shown that erythropoietin (EPO) has a critical role in the development, maintenance, protection and repair of the nervous system. In the present study we investigated the effect of EPO on LPS-induced WM injury in Sprague-Dawley rats. LPS (500 µg/kg) suspension in pyrogen-free saline was administered intraperitoneally to pregnant rats at 18 and 19 days of gestation. The control group was treated with pyrogen-free saline. They were given 5,000 U/kg recombinant human EPO. Seven-day-old Sprague-Dawley rat pups were divided into four groups: control group, LPS-treated group, prenatal maternal EPO-treated group (5,000 U/kg, intraperitoneally given to pregnant rats at 18 and 19 days of gestation), and postnatal EPO-treated group (5,000 U/kg, intraperitoneally given to 1-day-old rat pups). Cytokine induction in the postnatal 7-day-old (P7) rat brain after maternal administration of LPS was determined by the ELISA method. The proinflammatory cytokine levels (IL-1β, TNF-α, and IL-6) in P7 rat pup brains were significantly increased in the LPS-treated group as compared with the control group. Prenatal maternal EPO treatment significantly reduced the concentration of TNF-α and IL-6 in the newborn rat brain following LPS injection. The concentration of IL-1β was decreased in the intrauterine EPO treatment group. Postnatal EPO treatment significantly decreased only the IL-6 concentration in the newborn rat brain following LPS injection. The concentration of cytokines, IL-1β and TNF-α, was reduced in the postnatal EPO treatment group. We demonstrated here that LPS administration in pregnant rats at gestational day 18 and 19 induced WM injury in P7 progeny characterized by apoptosis. Prenatal maternal and postnatal EPO treatment significantly reduced the number of apoptotic cells in the periventricular WM. Using immunohistochemistry techniques, we investigated the effects of maternal administration of LPS on myelin basic protein (MBP) staining, as a marker of myelination in the periventricular area in the neonatal rat brain. MBP staining was significantly less and weaker in the brains of the LPS-treated group as compared with the prenatal maternal EPO-treated group. However, the postnatal EPO treatment did not prevent LPS-stimulated loss of MBP-positive staining. In conclusion, especially prenatal maternal EPO treatment attenuates LPS-induced injury by reducing the expression of inflammatory cytokines and sparing MBP in the neonatal rat brain. While the postnatal EPO treatment prev...

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Theory of Mind (ToM) may be defined as the ability to understand the mental states, such as beliefs, desires, intentions, and emotions, of others. Impairment of ToM ability leads to disorders with pathologies in social skills, such as autism spectrum disorder and schizophrenia. In addition to differences in ToM ability among patient populations, there is variation between neurotypical individuals. Unfortunately, ToM tasks are usually developed for children or patients with cognitive disorders and cannot detect variations in healthy adults. As an alternative tool, humor may be used. Humor plays a role in social communication and requires many different cognitive functions. Humor is believed to represent complex high-order cognitive processes. There are numerous types of humor; the most complex type is considered ToM humor, where an understanding of social/emotional content is necessary. Given the need for a ToM assessment test suitable for healthy adult populations, we developed a test for measuring humor comprehension and appreciation, with and without ToM content (ToM-HCAT). The present ToM-HCAT test is a performance test consisting of cartoons. The test measures perceived funniness, reaction time to perceived funniness decision, and meaning inference. Cartoons were selected after pilot studies involving 44 participants. Subscales were constituted according to expert views and confirmed by confirmatory factor analysis (N = 135). Goodness of fit values for the final 35-item test were acceptable to excellent: GFI = 0.97; AGFI = 0.97; NFI = 0.97; RFI = 0.97, and SRMR = 0.067. Both categories were internally consistent (α1 = 0.84, α2 = 0.94). External validity was assessed against autistic traits. One hundred and three participants completed the Autism Spectrum Quotient and were grouped by +0.5 standard deviations from the mean as high in autistic traits. The meaning-inference scores of the subscale with the ToM cartoons were significantly lower (p = 0.034) for the high autistic traits group, providing evidence of external validity. In conclusion, we developed and validated a test for assessment of ToM by humor comprehension and appreciation. We believe that the present test will be useful for the detection of variations in ToM ability in the healthy adult population.

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