Neuroscience
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The effects of hypothermia on ischemia-reperfusion injury of the cochlea were studied in gerbils. Hearing was assessed by sequentially recording compound action potentials before, during and after the ischemia. The degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and the dye Hoechst 33342. ⋯ In the ischemia/hypothermic group, the threshold returned to the pre-ischemic level within 30 min after reperfusion and remained stable thereafter. The mean loss of inner and outer hair cells on the seventh day was 0.1 % and 0.2 %, respectively. These results indicate that hypothermia can prevent inner ear damage, which otherwise occurs after transient ischemia of the cochlea.
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The pathophysiology of brain ischemia and reperfusion injury involves perturbation of intraneuronal ion homeostasis. To identify relevant routes of ion flux, rat hippocampal slices were perfused with selective voltage- or ligand-gated ion channel blockers during experimental oxygen-glucose deprivation and subsequent reperfusion. Electron probe X-ray microanalysis was used to quantitate water content and concentrations of Na, K, Ca and other elements in morphological compartments (cytoplasm, mitochondria and nuclei) of individual CA1 pyramidal cell bodies. ⋯ Na+ channel blockade also effectively diminished neuronal ion and water derangement during oxygen-glucose deprivation and reperfusion. Prevention of elevated Nai+ levels is likely to provide neuroprotection by decreasing presynaptic glutamate release and by improving cellular osmoregulation, adenosine triphosphate utilization and Ca2+ clearance. Thus, we suggest that voltage-gated tetrodotoxin-sensitive Na+ channels and glutamate-gated ionotropic NMDA or AMPA receptors are important routes of ion flux during nerve cell injury induced by oxygen-glucose deprivation/reperfusion.
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We report a novel gene transfer system using electroporation. We used this technique to introduce a marker gene plasmid containing enhanced green fluorescent protein into mouse brains at embryonic day 12-17 without removing the embryos from the uterus. The embryos were allowed to continue to develop in utero, and more than 80% were born normally expressing the exogenous gene. ⋯ By contrast, when elongation factor 1alpha promoter was used, prominent fluorescence allowed visualization of the entire mature neurons as well. The labeled neurons were observed to send axons to the contralateral cortex where they arborized extensively. Thus, this system is much easier and more efficient than virus-mediated gene transfer, and is useful for gain-of-function analysis of neural cell fate determination, migration, positioning and axon path-finding in mouse embryos.
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Midbrain sections taken from Sprague-Dawley rats of varying ages within the first four postnatal weeks were used to determine, immunocytochemically, putative changes of GABA(A) receptor beta2/3 subunits, GABA(B) receptor (R1a and R1b splice variants), and GABA(C) receptor rho1 subunit expression and distribution in the superficial, visual layers of the superior colliculus. Immunoreactivity for the GABA(A) receptor beta2/3 subunits was found in the superficial grey layer from birth. The labelling changed with age, with an overall continuous reduction in the number of cells labelled and a significant increase in the labelling intensity distribution (neuropil vs soma). ⋯ In conclusion, all three GABA receptor types were found to be present in the superior colliculus from birth, and all show some form of postnatal modification, with GABA(A) receptors demonstrating the most dramatic changes. However, GABA(B) and GABA(C) receptors are modified significantly around the onset of input-specific activity. Together, this points towards a contribution of the GABAergic system to processes of postnatal maturation in the superficial superior colliculus.
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Neurturin and glial cell line-derived neurotrophic factor are novel mitogens for normal adult rat chromaffin cells in vitro. These neurotrophic factors differ from the previously described adult chromaffin cell mitogens, nerve growth factor and basic fibroblast growth factor, in that their effects are potentiated by depolarization and activation of protein kinase C. Neurturin and glial cell line-derived neurotrophic factor signal via the receptor tyrosine kinase, ret, but may also act independently of ret. ⋯ Inhibitors of phosphatidylinositol 3-kinase also prevent mitogenesis. The present findings suggest the hypothesis that neurotrophic factors and neurally derived signals might cooperatively regulate chromaffin cell proliferation in vivo in the rat. In addition, trans-synaptic stimulation might provide a route by which epigenetic factors could influence the development of adrenal medullary hyperplasia in humans with hereditary multiple endocrine neoplasia syndromes 2A and 2B by affecting expression and/or activation of ret.