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Kainate enhances hippocampal precursor cell proliferation and survival in vitro, while Kainate induced seizures additionally recruits quiescent progenitors in vivo
No full textIt is widely accepted that hippocampal neurogenesis persists throughout life and is altered by acute seizures. Kainate is often used to model temporal lobe epilepsy and hippocampal damage. Kainate-induced status epilepticus transiently enhances hippocampal neurogenesis but the mechanisms are not well understood. Therefore, we examined the effects of Kainate on hippocampal precursors in vitro. We also investigated the acute effects of Kainate/seizures on a pre-labelled clone of proliferating hippocampal precursors in vivo.
Cultured hippocampal cells were prepared from Wistar rats P7-10 and exposed to 5µM Kainate. BrdU and Ki-67 were used to measure cell proliferation while caspase-3, Propidium iodide, MitoTracker, and Time-lapse microscopy were used to study cell survival. Nestin and TuJ1 were used to label precursor cells and neuroblasts, respectively. To examine Kainate effects in vivo, a clone of proliferating cells in the dentate gyrus was pre-labelled with BrdU 24 hours before Kainate-induced status epilepticus and examined 6-72 h later.
In vitro, we found that Kainate increased the proliferation rate of nestin-positive postnatal hippocampal precursors, via AMPA receptors. It also enhanced the survival of nestin and TuJ1 cells with a proportional increase in neuroblasts. Consistently, Kainate/seizures in vivo increased cell proliferation in the subgranular zone (SGZ) and granule cell layer (GCL) of the adult dentate gyrus, without enhancing cell death. Kainate/seizures recruited un-labelled quiescent cells in the SGZ. In contrast it increased the proliferation of the pre-labelled population only in the GCL. Kainate/seizures drove significantly more BrdU+ cells to become postmitotic in the GCL but not in the SGZ. Doublecortin positive cells increased in the GCL by 72 h after Kainate.
We conclude that Kainate enhances hippocampal precursor proliferation and survival without increasing cell death, while seizures recruit a quiescent cell population in the SGZ
Plasticity of neuropeptide Y in the dentate gyrus alter seizures, and its relevance to seizure-induced neurogenesis
No full textIn summary, NPY is clearly an important peptide in the adult rat dentate gyrus because it has the potential to influence synaptic transmission and neurogenesis. It may even have other functions, as yet undiscovered, mediated by glia or vasculature. The remarkable plasticity of NPY puts it in a position to allow dentate gyrus function to be modified in a changing environment. The importance of this plasticity in the context of epilepsy cannot be emphasized enough. It could help explain a range of observations about epilepsy that currently is poorly understood. For example, rapid increases in NPY could mediate postictal depression, the period of depression that can last for several hours after generalized seizures. It may mediate the "priming effect," which is a reduction in seizure threshold following an initial period of seizures. Finally, it could contribute to the resistance of dentate granule cells to degeneration after seizures. However, despite the focus in this review on seizure-induced changes, the changes described here also appear to occur after other types of manipulations, which considerably broadens the scope of NPY's role in the brai
Intraoperative optical measurement of function in the human brain
No full textIntraoperative determination of function is important to surgeons to maximize the outcome of surgery, for example the extent of tumor resection, and minimize post-surgical deficit. This paper will outline the continued work developing a camera system sensitive to tissue blood oxygen level. Tissue blood oxygen level although not a direct measure of activation is exploited by functional MRI (fMRI) to infer eloquence and has a high correlation with other techniques. Current intraoperative techniques such as electro-cortical stimulation use an alternating electrical current to inhibit brain function in the area it is applied. The patient is then required to perform a task or report sensation; this takes time and provides a rather limited resolution (typically about 5mm). Preoperative techniques such as fMRI and PET suffer from poor spatial resolution (typically 4mm) and more importantly registration issues as brain tissue can move by as much as 15mm during surgery. The camera system images the entire surgical field at a high resolution and may provide the surgeon with real-time information. Initially data was collected using a free standing camera optimized for high signal to noise. These results showed a high correlation with electro-cortical stimulation. The latest development of this camera has seen it attached to a Zeiss surgical microscope to provide an improved perspective on the surgical field. Results from this system are expected shortly and are expected to establish a strong correlation with current techniques and to provide real-time information
Seizure induced dentate neurogenesis does not diminish with age in rats
No full textNeurogenesis in the mammalian dentate gyrus occurs throughout life, is believed to be important for the laying down of episodic memory and diminishes significantly with increasing age. Pathological insults such as seizures, hypoxia and traumatic brain injury increase dentate neurogenesis compared to age matched controls. Using unilateral intracerebroventricular kainate we show that although baseline neurogenesis is significantly lower in 3 month old rats compared to 1 month old rats, kainate increases neurogenesis to reach similar levels in both age groups. Additionally, this effect is bilateral after a unilateral intracerebroventricular kainate injection. We conclude that the potential for dentate neurogenesis is maintained despite diminishing baseline levels with increasing age and that injury signals override the age related suppression of neurogenesis
Kainic acid induces rapid cell death followed by transiently reduced cell proliferation in the immature granule cell layer of rat organotypic hippocampal slice cultures
No full textBrain injury due to seizures results in transiently increased cell proliferation and neurogenesis in the subgranular zone of the adult dentate gyrus. In contrast, the immature postnatal brain appears to be more resistant to cell death after seizure-induced brain injury and paradoxically reacts to seizures by reducing SGZ proliferation. Organotypic hippocampal slice cultures are a useful paradigm for modelling the early postnatal hippocampus. We have investigated the temporal relationship between cell death and cell proliferation after kainate in the granule cell layer of rat organotypic hippocampal slice cultures equivalent to post natal day 11 animals. We found stable numbers and densities of mature thionine stained cells in the granule cell layer over 72 h in control cultures grown in defined medium. We also found a slowly declining cell proliferation rate over the same time period under control conditions. We report evidence of early cell death in the granule cell layer after just 2 h exposure to 5 AM kainate, followed by a significant decrease in cell proliferation in the granule cell layer at 24 h. In contrast to control conditions, cell proliferation rose significantly in the kainate exposed cultures by 72 h back to levels seen at 2 h. There were no significant changes in cell labelling with antibody to activated caspase-3 between kainate treated and control cultures at any time point examined. Our results suggest that kainate-induced injury in the early postnatal hippocampus damages precursor cells contributing to a reduction in granule layer cell proliferation
Persistent and intractable ventriculitis due to retained ventricular catheters
No full textIt is generally recommended that, in cases of difficulty in removing a ventricular catheter during a shunt revision, it is best left alone to avoid intraventricular haemorrhage. Retained ventricular catheters (RVCs) are usually safe, although in the presence of ventriculitis they may become colonized by organisms and become a source of persistent or recurrent infection. The authors present a case of persistent and intractable ventriculitis due to an old retained ventricular catheter. A 23-year-old female, who had a RVC and a functioning shunt, was admitted for a suspected blocked shunt. At surgery the shunt was found to be infected and external drainage was instituted. Over the next 4 months, she developed intractable and persistent staphylococcal ventriculitis, despite undergoing 10 further surgical procedures, and appropriate intravenous and intrathecal antibiotic therapy. She responded rapidly only after surgical removal of the old RVC via a craniotomy. The staphylococcus cultured from the RVC had an identical antibiogram to the organism responsible for the intractable ventriculitis. This case emphasizes the point that, although RVC are generally considered safe, removal becomes imperative in the presence of concurrent CSF infection that fails to respond quickly to intrathecal antibiotic therapy
VIP: Interactions with NPY and FGF-2 in the modulation of postnatal hippocampal neurogenesis
No full textVasoactive intestinal peptide (VIP) is a 28 amino acid polypeptide that is a modulator of neurodevelopment. High levels of VIP and its receptors have been found in postnatal mammalian hippocampus and are influenced by different physiological and pathological conditions such as exercise, stress, spatial learning and epilepsy, which also affect hippocampal neurogenesis. We are investigating the hypothesis that VIP modulates the survival, proliferation and differentiation of stem cells and their progeny in the postnatal hippocampus.We have investigated the effect of VIP alone or in conjunction with NPY or FGF-2 in primary hippocampal neuronal cultures from postnatal rats (P7–9). Bromodeoxyuridine (BrdU) and Ki-67 were used as markers of cell proliferation. Ara-C was used to inhibit cell proliferation. Quantification of cell death was achieved using the nuclear stain 4?,6-diamidino-2-phenylindole (DAPI) and the cell death marker propidium iodide (PI). Immunohistochemistry was used to phenotype cells for nestin, GFAP, and class-III beta-tubulin.We have shown that VIP enhances the survival of postnatal nestin positive hippocampal stem cells and their progeny in a dose dependent manner. At micromolar concentrations, VIP increased cell proliferation and the labelling index. However, at nanomolar concentrations, we observed a purely trophic effect on both mitotic and non-mitotic cells. When cells were exposed to VIP in conjunction with the mitogens NPY or FGF-2, VIP abolished and decreased their proliferative effects respectively. Interestingly, the proportion of neuroblasts increased under VIP plus NPY conditions while the number of progenitor cells increased under VIP plus FGF-2 conditions.We conclude that VIP may be an important trophic factor for hippocampal neurogenesis and interacts with NPY and FGF-2 to modulate the proliferation of stem cells and the survival of their progeny. We suggest that these neuropeptides and others provide a novel control system for postnatal hippocampal neurogenesis depending on their differential release.<br/
Phase synchronization with ICA for epileptic seizure onset prediction in the long term EEG
No full textThe apparently unpredictable nature of epileptic seizures can be devastating for people with epilepsy. Current medical interventions can help 75% of patients while 25% have to live with uncontrolled seizures. This motivates the search for a seizure prediction prototype using electroencephalograms (electrical signals that capture brain activity). The concept of phase synchrony has attracted much attention recently in the context of seizure prediction but is still in need of further study. The basis of our analysis is to track changes in synchrony in brain signals at and before seizure onset. The novel concept in our analysis is the use of unmixed signals as opposed to scalp EEG signals for phase synchrony analysis. The unmixing is performed by a Blind Source Separation technique called Independent component Analysis (ICA). ICA seeks underlying independent source signals from the EEG and it allows multivariate analysis using spatial as well as temporal information inherent to EEG signals. The present study on long-term continuous EEG data sets indicates that the concept of using phase synchronization with ICA may prove useful for predicting seizures
Interrater reliability of Engel, International League Against Epilepsy, and McHugh seizure outcome classifications following vagus nerve stimulator implantation
No full textOBJECT: Interrater reliability as measured by the kappa (?) statistic is a widely used and valuable tool to measure the robustness of a scoring system. Seizure frequency reduction is a central outcome measure following vagus nerve stimulation (VNS). A specific VNS scoring system has been proposed by McHugh, but its interrater reliability has not been tested. The authors assessed its interrater reliability and compared it with that of the Engel and International League Against Epilepsy (ILAE) systems.METHODS: Using the Engel, ILAE, and McHugh scoring systems, 3 observers independently rated the medical records of children who had undergone vagus nerve stimulator implantation between January 2001 and April 2011 at the Southampton University Hospital. The interrater agreements were then calculated using the ? statistic.RESULTS: Interrater reliability for the McHugh scale (?0.693) was very good and was superior to those of the Engel (?0.464) and ILAE (?0.491) systems for assessing outcome in patients undergoing VNS.CONCLUSIONS: The authors recommend considering the McHugh scoring system when assessing outcomes following VNS
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