Brain research
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In vivo, preconditioning with a sublethal insult can confer resistance to normally lethal episodes of cerebral ischaemia. This phenomenon has been linked with the induction of the 72 kDa heat shock protein (HSP72), but this has not been clearly demonstrated in vitro. We have used organotypic hippocampal slice cultures to investigate whether tolerance to lethal ischaemia is dependent on HSP72. ⋯ Preconditioning with 1 microM NMDA significantly reduced neuronal damage produced by either 45 or 60 min ischaemia when the delay between insults was 48 h. NMDA pre-treatment also prevented neurotoxicity produced by glutamate (5-10 mM) but not NMDA (10-30 microM). These data suggest that in vitro, the increased expression of HSP72 following some sublethal insults should be considered as a marker of cell stress prejudicial to the survival of neurones subsequently exposed to ischaemia, while tolerance can be produced through mechanisms independent of HSP72 induction.
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To study the roles of peripheral excitatory amino acids receptor subtypes N-methyl-D-aspartate (NMDA) and non-NMDA receptors in persistent nociception, extracellular single unit recording technique was used to assess the effects of a single dose NMDA and non-NMDA receptor antagonists, AP(5) (5-aminophosphonovaleric acid) and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) or DNQX (6,7-dinitroquinoxaline-2,3-dione), on s.c. bee venom-induced increase in firing of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of the urethane-chloralose anesthetized cats. Subcutaneous bee venom injection into the cutaneous receptive field resulted in a single phase of increased firing of WDR neurons over the background activity for more than 1 h. Local pre-administration of AP(5) (200 microg/100 microl) or CNQX (8.3 microg/100 microl) into the bee venom injection site produced 94% (1.01+/-0.96 spikes/s, n=5) or 76% (2.97+/-0.58 spikes/s, n=4) suppression of the increased neuronal firing when compared with local saline (16.32+/-4.55 spikes/s, n=10) or dimethyl sulfoxide (DMSO) (12.37+/-6.36 spikes/s, n=4) pre-treated group, respectively. ⋯ In the control experiments, local pre-administration of the same dose of AP(5) or CNQX into a region on the contralateral hindpaw symmetrical to the bee venom injection site produced no significant influence on the increased firing of the WDR neurons [contralateral AP(5) vs. saline: 14.17+/-6.27 spikes/s (n=5) vs. 16.32+/-4.55 spikes/s (n=10), P0.05; contralateral CNQX vs. DMSO: 12.85+/-6.38 spikes/s (n=4) vs. 12. 37+/-6.36 spikes/s (n=4), P0.05], implicating that the suppressive action of local AP(5) or CNQX was not the result of systemic effects. The present results suggest that activation of the peripheral NMDA receptors is involved in both induction and maintenance, while activation of non-NMDA receptors is only involved in induction, but not in the maintenance of persistent firing of the dorsal horn WDR neurons induced by s.c. bee venom injection.
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Alterations in the expression of growth-associated protein 43 (GAP-43) were examined in lower urinary tract micturition reflex pathways in a chronic model of cyclophosphamide (CYP)-induced cystitis. In control animals, expression of GAP-43 was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the dorsal horn and (3) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1) and (4) in the lateral collateral pathway of Lissauer in L6-S1 spinal segments. Densitometry analysis has demonstrated significant increases (p
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Small reductions in temperature have been shown to improve neurologic recovery after ischemia. We have examined the effect of temperature on biochemical and physiological changes during hypoxia using rat hippocampal slices as a model system. The postsynaptic population spike recorded from the CA1 pyramidal cell region of slices subjected to 7 min of hypoxia with hypothermia (34 degrees C) recovered to 73% of its prehypoxic level; slices subjected to the same period of hypoxia at 37 degrees C did not recover. ⋯ Potassium fell to 76% after 3 min of hypoxia with hyperthermia, this compares to 91% at 37 degrees C. Sodium concentrations increased with hyperthermia before hypoxia, at 3 min of hypoxia there was no significant difference between the hyperthermic and normothermic tissue; there was a large increase in sodium with hyperthermia after 5 min of hypoxia (209% vs. 146%). We conclude that the improved recovery after hypothermic hypoxia is at least in part due to the attenuated changes in ATP, potassium and sodium during hypoxia and that the worsened recovery with hyperthermia is due to an exacerbation of the change in ATP, potassium and sodium concentrations during hypoxia.
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A multiplicative antinociceptive interaction of morphine activity at supraspinal and spinal sites has been clearly established and is thought to be responsible, in part, for the clinical utility of this compound in normal dose-ranges. While synergistic actions of mu-opioid receptor agonists have been shown, it is unclear whether a similar interaction exists for opioid agonists acting via delta-opioid receptors. Responses to acute nociception were determined with the 52 degrees C hot plate, 52 degrees C warm-water tail-flick and the Hargreaves paw-withdrawal tests. ⋯ Both of the opioid delta agonists produced dose-dependent antinociception in all tests. With the exception of DPDPE in the hot plate test, isobolographic analysis revealed that the supraspinal/spinal antinociceptive interaction for both DPDPE and DELT were synergistic in all nociceptive tests. These data suggest that opioid delta agonists exert a multiplicative antinociceptive interaction between supraspinal and spinal sites to acute noxious stimuli and suggest possibility that compounds acting through delta-opioid receptors may have sufficient potency for eventual clinical application.