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The tumor suppressor p53 and its response gene p21(WAF1/Cip1) are not markers of neuronal death following transient global cerebral ischemia
The tumor suppressor protein p53 is implicated in cell cycle arrest and DNA repair as well as in apoptosis. In the CNS, p53 has been associated with neuronal cell death following various insults, including cerebral ischemia. We investigated the expression of p53 messenger RNA and protein, and the messenger RNA expression of the p53-responsive gene p21(WAF1/Cip1), in specific hippocampal regions fo
Changes in proliferating cell nuclear antigen, a protein involved in DNA repair, in vulnerable hippocampal neurons following global cerebral ischemia
Proliferating cell nuclear antigen (PCNA) is required for completion of the DNA synthesis step of DNA replication as well as nucleotide excision repair (NER) of damaged DNA. We investigated the expression of PCNA mRNA and the levels of PCNA protein in the adult rat hippocampus following normo- and hypothermic global forebrain ischemia. Hypothermia protected the CA1 neurons from ischemic damage. A
The effect of 4β-phorbol-12,13-dibutyrate and staurosporine on the extracellular glutamate levels during ischemia in the rat striatum
Hypothermia diminishes the ischemia-induced protein kinase C (PKC) translocation and inhibition, and also reduces transmitter release during ischemia. To study the role of PKC in the mechanism of glutamate release during ischemia, we measured extracellular glutamate levels in the striatum with the microdialysis technique, in the presence and absence in the dialysate of the PKC activator 4β-phorbol
Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death
Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells. Treatm
The effect of hypothermia on the expression of neurotrophin mRNA in the hippocampus following transient cerebral ischemia in the rat
The expression of the mRNAs of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3) and the neurotrophin receptor, TrkB, was studied in the rat hippocampus by in situ hybridization following normothermic (37°C) and protective hypothermic (33°C) transient cerebral ischemia of 15 min duration. In the resistant dentate gyms, normothermic ischemia transiently induc
Changes in the extracellular levels of glutamate and aspartate during ischemia and hypoglycemia. Effects of hypothermia
Hypothermia (33°C) dramatically diminishes ischemic but not hypoglycemic brain damage. The beneficial effects of hypothermia in ischemia have been partly attributed to a reduction in the ischemia-induced increase in synaptic levels of glutamate or aspartate. With the microdialysis technique, we studied the effects of hypothermia (33°C) on the brain extracellular levels of glutamate and aspartate d
Novel pharmacologic strategies in the treatment of experimental traumatic brain injury : 1998
The mechanisms underlying secondary or delayed cell death following traumatic brain injury are poorly understood. Recent evidence from experimental models suggests that widespread neuronal loss is progressive and continues in selectively vulnerable brain regions for months to years after the initial insult. The mechanisms underlying delayed cell death are believed to result, in part, from the rele
Regional selective neuronal degeneration after protein phosphatase inhibition in hippocampal slice cultures : Evidence for a MAP kinase-dependent mechanism
The regional selectivity and mechanisms underlying the toxicity of the serine/threonine protein phosphatase inhibitor okadaic acid (OA) were investigated in hippocampal slice cultures. Image analysis of propidium iodide-labeled cultures revealed that okadaic acid caused a dose- and time- dependent injury to hippocampal neurons. Pyramidal cells in the CA3 region and granule cells in the dentate gyr
Sublethal in vitro glucose-oxygen deprivation protects cultured hippocampal neurons against a subsequent severe insult
Rat and gerbil hippocampus exposed to a sublethal period of ischemia becomes resistant to a subsequent period of lethal ischemia induced several days later, a phenomenon referred to as ischemic preconditioning. Here we describe ischemic preconditioning induced in vitro in cultured hippocampal neurons. Mixed neuroglial hippocampal cell cultures of 14-17 DIV were exposed to a combined glucose and ox
High resolution immunogold analysis reveals distinct subcellular compartmentation of protein kinase Cγ and δ in rat Purkinje cells
High resolution immunogold cytochemistry was used to investigate the subcellular distribution of protein kinase Cγ and δ in Purkinje cells of the rat cerebellum. Postembedding incubation with an antibody raised to a peptide sequence near the C-terminus of protein kinase Cγ resulted in strong labelling along the dendrosomatic plasma membrane. A quantitative analysis indicated that this labelling re
Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia
It has been shown that changes in body core temperature several hours after a transient ischemic insult affect neuronal survival. We report that body core temperature in normal rats fluctuates over a 24-h period, while in rats subjected to 10 min transient ischemia induced by occlusion of the common carotid arteries in combination with hypotension, body temperature persistently increases to above
Induction of junD mRNA after transient forebrain ischemia in the rat. Effect of hypothermia
The expression of junD was studied in the rat hippocampus by in situ hybridization after 15 min of normothermic (37°C) and hypothermic (33°C) transient forebrain ischemia. Ischemia was induced by common carotid artery occlusion combined with hypotension leading to damage in the CA1 region of the hippocampus which was prevented by hypothermia junD mRNA was induced in the hippocampus within 2 h of r
Fieldwork in Grey Zones : A case study on organ trafficking in the Philippines
In this chapter I present a multi-sited fieldwork set in the Philippines that examines trade in organs from living individuals. The organ commerce generally involves organs harvested from living persons. Since humans have two kidneys and can survive with one, it is primarily kidneys that are transplanted, but also illegally traded. Here, my focus is solely on kidney transplantation. The ambition i
Development of stable haploid strains and molecular genetic tools for Naumovozyma castellii (Saccharomyces castellii)
The budding yeast Naumovozyma castellii (syn. Saccharomyces castellii) has been included in comparative genomics studies, functional analyses of centromere DNA elements, and was shown to possess beneficial traits for telomere biology research. To provide useful tools for molecular genetic approaches, we produced stable haploid heterothallic strains from an early ancestral strain derived from the N
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Subcellular distribution and autophosphorylation of calcium/calmodulin- dependent protein kinase II-α in rat hippocampus in a model of ischemic tolerance
A brief period of sublethal ischemia induces resistance to a subsequent, otherwise lethal, ischemic insult, a process named ischemic tolerance or preconditioning. A persistently disturbed cell signaling during reperfusion after cerebral ischemia has been proposed to contribute to ischemic cell death. Here, we report on the effect of ischemic preconditioning on the levels of the regulatory α-subuni
Increased survival of embryonic nigral neurons when grafted to hypothermic rats
Hypothermia can reduce neuronal death caused by ischemia and traumatic brain injury. We therefore investigated whether mild hypothermia in rats receiving a transplant of embryonic mesencephalic rat tissue increases survival of the implanted dopaminergic neurons. Mild hypothermia (32-33°C) during graft implantation and for the following 90 min significantly increased the survival of transplanted do
The effect of α-phenyl-tert-butyl nitrone (PBN) on free radical formation in transient focal ischaemia measured by microdialysis and 3,4-dihydroxybenzoate formation
α-phenyl-tert-butyl nitrone (PBN) reduces infarct size, improves recovery of brain energy metabolism and delays the secondary increase in extracellular potassium after focal ischaemia, presumably by trapping OH radicals. We investigated the effect of PBN on the formation of 3,4-dihydroxybenzoic acid (3,4-DHBA) as a measure of OH radical formation, during and following middle cerebral artery occlus
There's more to the multimedia effect than meets the eye : is seeing pictures believing?
Textbooks in applied mathematics often use graphs to explain the meaning of formulae, even though their benefit is still not fully explored. To test processes underlying this assumed multimedia effect we collected performance scores, eye movements, and think-aloud protocols from students solving problems in vector calculus with and without graphs. Results showed no overall multimedia effect, but i