1,721,008 research outputs found

    Gender differences in febrile seizure-induced proliferation and survival in the rat dentate gyrus

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    Purpose: Febrile seizures are fever-associated early-life seizures that are thought play a role in the development of epilepsy. Seizure-induced proliferation of dentate granule cells has been demonstrated in several adult animal models and is thought to be an integral part of epileptogenesis. The aim of the present study was to investigate proliferation and survival of dentate gyrus (DG) cells born after early-life hyperthermia (HT)-induced seizures in male and female rats. Methods: At postnatal day (PN) 10, male and female rats were exposed to heated air to induce seizures. Littermates were used as normothermia controls. Convulsive behavior was observed by two researchers. From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. The number of BrdU-immunoreactive cells in the DG was counted at PN17 and PN66. Results: At PN17, male as well as female HT rats had the same amount of BrdU-positive cells compared with controls. At PN66, significantly more BrdU-positive cells were left in HT females (53%) than in controls (44%, percentage of BrdU-positive cells at PN17), whereas no difference was found between HT males and male controls. The net result of proliferation and survival at PN66 was that female HT rats had the same number of BrdU-immunoreactive cells as controls, whereas male HT rats had 25% more BrdU-immunoreactive cells than did controls (p < 0.05). Conclusions: Early-life seizures cause a sexually dimorphic cytogenic response that results in an increased population of newborn DG cells in young adult males, while leaving that of young adult females unaltered

    Cytogenesis in the dentate gyrus after neonatal hyperthermia-induced seizures: What becomes of surviving cells?

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    Purpose: Febrile seizures (FS) are early-life seizures thought to play a role in epileptogenesis. By labeling cells that were dividing immediately following experimental FS, we previously demonstrated that significantly more of these newborn cells in the dentate gyrus (DG) survived 8 weeks later, relative to animals that did not experience FS. The purpose of the present study was to determine the long-term fate of these newborn cells. Methods: On postnatal day (PN) 10, hyperthermia-induced seizures (HT, +/- 42 degrees C core temperature) were evoked in Sprague-Dawley rats and littermates were used as normothermia controls (NT, +/- 35 degrees C core temperature). From PN11 to PN16, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. At PN66, we evaluated the number of BrdU-labeled cells in the DG that colocalized with the neuronal marker NeuN, glial marker glial fibrillary acidic protein (GFAP), neuronal excitatory amino acid transporter 3 (EAAT3), GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67) or microglia marker tomato lectin (TL). Results: In all rats, almost all BrdU-labeled cells in the DG, that showed double-labeling, colocalized with NeuN, and rarely with GFAP, GAD67, or TL. In NT controls and HT rats that did not experience seizures ("HT-no seizures"), similar to 23% of BrdU-labeled cells colocalized with EAAT3, which was significantly different from 14% in HT rats that did experience seizures (HT + FS). Discussion: Early-life seizures decrease the population of newborn cells that survive and mature into EAAT3-positive neurons and do not affect the GABAergic cell population. This may affect hippocampal physiology in young adulthood

    Neural stem cells and interleukin-13 as a combination therapy for spinal cord injury

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    In this study, we have combined the immunomodulatory and regenerative properties of neural stem cells (NSCs) and interleukin-13 (IL-13) as a therapeutic strategy for spinal cord injury (SCI). NSC transplantation alone will most likely not be successful without the application of additional factors which modulate the environment to make it more supportive and permissive for endogenous neural regeneration. We hypothesized that NSCs and IL-13, alone or in combination, induce a significant improvement in clinical and histological outcome after SCI by modulating the inflammatory response. Firstly, we investigated whether the transplanted eGFP-positive NSCs survived after grafting into the spinal cord lesion, as well as measuring the clinical and histological outcome. Secondly, eGFP-positive NSCs were injected into the spinal cord lesion of mice, followed by the addition of an IL-13 containing gelfoam. Clinical outcome and survival of the transplanted NSCs were again determined

    Using stem cells as carriers of IL-4 to promote recovery after spinal cord injury

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    Spontaneous regeneration of the CNS after spinal cord injury (SCI) is limited, due to intrinsic inhibition of neuroregeneration, but also resulting from SCI-associated inflammation. Therefore, research on new therapeutic strategies focuses on modulation of this inflammatory response. We hypothesize that the immunomodulatory and regenerative functions of IL-4-producing stem cells (SCs) promote axon regeneration and SC-survival to improve functional recovery after SCI. To investigate this hypothesis, IL-4 secreting BMSCs will be used in a pilot study to investigate whether the use of SCs is a good way of delivering IL-4 to the site of injury to promote recovery after SCI, as measured by functional tests. Meanwhile, the NSCs will be characterized and transduced for their use in future experiments. Furthermore, the effect of recombinant mouse IL-4 treatment on the viability and the phenotype of NSCs will be investigated in vitro
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