Neuroscience
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Astrocytes become activated in degenerative neurological diseases. In order to gain a greater understanding of the inflammatory factors released upon activation, we stimulated adult human astrocytes with interferon-gamma and examined the resultant conditioned medium (CM) for toxicity against differentiated human neuroblastoma SH-SY5Y cells. Cell death was measured by lactate dehydrogenase release assay. ⋯ This was in reasonable agreement with the 85.37% total obtained by adding the individual components. The data show that activated astrocytes release a specific combination of neurotoxic compounds. They suggest that effective anti-inflammatory treatment of such neurodegenerative diseases as Alzheimer's disease, Parkinson's disease and Amyotrophic lateral sclerosis could be improved by using an appropriate combination of anti-inflammatory agents instead of relying on any single agent.
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Neural stem cells, which reside mainly in the subventricular and subgranular zones of the hippocampus, can regenerate new neuroblasts after various brain insults. Aided by vascular remodeling, these new neuroblasts migrate long distances to injured brain regions. ⋯ Daily administration of ethyl pyruvate, which inhibited HMGB1 expression, reduced the recovery of neurological function, decreased vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) levels in the ipsilateral striatum, and decreased the numbers of 5-bromo-2-deoxyuridine (BrdU)- and doublecortin (DCX)-positive cells around the hematoma. These findings suggest that HMGB1 may promote angiogenesis and neurogenesis in the late phase of ICH.
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Stanniocalcin 1 (STC1), originally described as an antihypercalcemic hormone in fish, is highly expressed in differentiated mammalian neurons. Mild hypoxic treatment and focal cerebral ischemia induce upregulation of STC1 in the brain. These findings prompted us to investigate whether STC1 contributes to neuroprotection after ischemia and whether STC1 is required for development of ischemic tolerance. ⋯ Ischemic STC1(-/-) mice showed significantly lower Il-6 mRNA expression than ischemic WT mice. Evans Blue fluorescence levels showed no difference in between WT and STC1(-/-) mice under evaluated conditions, thus BBB integrity is preserved despite STC1 deficiency. STC1 was not crucial for the development of ischemic tolerance triggered by HPC or for preserving BBB integrity but may be involved in functional recovery after stroke.
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Neuronal responses in primary visual cortex (V1) can be suppressed by a stimulus presented to the extraclassical surround, and such interactions are thought to be critical for figure ground segregation and form perception. While surround suppression likely originates from both feedforward afferents and multiple cortical circuits, it is unclear what role each circuit plays in the surround's orientation tuning. To investigate this we recorded from single units in V1 of anesthetized cat and analyzed the orientation tuning of the suppressive-surround over time. ⋯ While the tuning of the pinwheel cells plateaus at this point, tuning is enhanced further for domain cells, especially those located superficially in the cortex, reaching a peak at 80 ms from response onset. This relatively slow evolution of the orientation tuning of the suppressive surround suggests that fast-arriving feedforward circuits (10 ms) likely only provide broadly tuned suppression, but that feedback from higher visual areas which is likely to arrive over the next 30 ms and can cover both the receptive field center and the extraclassical surround contributes to the initial steep rise in tuning for both cell types. Moreover, we speculate that the even later enhancement in tuning for domain neurons could mean the involvement of inputs from relatively long-range lateral connections, which not only propagate slowly but also link like-oriented domains corresponding to the receptive field of only the extraclassical surround.
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Leptin microinjections into the nucleus of the solitary tract (NTS) have been shown to elicit sympathoexcitatory responses, and potentiate the cardiovascular responses to activation of the chemoreflex. In this study, experiments were done in Sprague-Dawley rats initially to provide a detailed mapping within the NTS complex of cells containing immunoreactivity to the long form of the leptin receptor (Ob-Rb). In a second series, this NTS region containing Ob-Rb immunoreactive cells was explored for single units antidromically activated by stimulation of pressor sites in the rostral ventrolateral medulla (RVLM). ⋯ In addition, 17 of these leptin responsive neurons were excited by the intra-carotid injections of KCN (80 μg/0.1 ml). Furthermore, the excitatory response of these single units to KCN was potentiated (59-83%) immediately following the leptin injection. These data indicate that leptin responsive neurons in NTS mediate chemoreceptor afferent information to pressor sites in the RVLM, and suggest that leptin may act as a facilitator on neuronal circuits within the NTS that potentiates the sympathoexcitatory responses elicited during the reflex activation of arterial chemoreceptors.