Simon Sydserff

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AZD0328, a novel spirofuropyridine neuronal nicotinic receptor partial agonist, was used to investigate the role of alpha7 neuronal nicotinic receptor (NNR) activation in the modulation of midbrain dopamine neuron function, cortical dopamine release and on two behavioral tasks known to be dependent on optimal levels of cortical dopamine. In vivo recordings(More)
1. The efficacy of the free radical trapping agent NXY-059 in reducing the infarct volume following both transient and permanent focal ischaemia has been examined in rats. 2. In the transient ischaemia model, rats were subjected to a 2 h occlusion of the middle cerebral artery (MCA). Intravenous infusion of NXY-059 (1, 10 and 30 mg kg(-1) h) for 21.75 h(More)
The creation of seizure-prone (Fast) and seizure-resistant (Slow) rat strains via selective breeding implies genetic control of relative seizure vulnerability, yet ample data also advocates an environmental contribution. To investigate potential environmental underpinnings to the differential seizure sensitivities in these strains, the authors compared(More)
We examined whether following a hypoxic-ischemic insult in young animals there are long-lasting functional deficits that correlate either to histological tissue damage or to potential compensatory plasticity changes. Four-week-old rats were subjected to an episode of cerebral hypoxia-ischemia (right carotid artery occlusion + 30 min of hypoxia) or a sham(More)
The purpose of the present study was to assess the magnitude and stability of a number of functional deficits in rats subjected to occlusion of the middle cerebral artery (MCAO). Three groups of rats, treated with 90-min, 120-min, or sham occlusion were used in functional studies for 22 weeks following surgery. The following tests were used:(More)
Use-dependent N-methyl-D-aspartate (NMDA) receptor antagonists protect neurons from the lethal consequences of excessive stimulation by excitatory amino acids. Clinical development of high-affinity compounds such as MK801 have been limited due to untoward side effects. Toward this end, the lower-affinity use-dependent NMDA antagonists have greater margins(More)
Αlpha-7 neuronal nicotinic receptors (NNRs) are considered targets for cognitive enhancement in schizophrenia and Alzheimer's disease. AZD0328 is an alpha-7 NNR partial agonist that enhances cognition in rodents and nonhuman primates at sub-microgram to microgram doses. We hypothesized that increased expression of the alpha-7 receptor contributes to this(More)
The effect of chlormethiazole on hemispheric swelling and cortical tissue water content has been investigated in a model of permanent middle cerebral artery (MCA) occlusion. Chlormethiazole (1 mmol/kg i.p.) or saline was administered 60 min after the induction of ischaemia and the animals sacrificed after 24 hours. The cross sectional area of the left(More)
The ability of chlormethiazole to protect against ischaemic cell damage in a rat model of permanent focal ischaemia has been examined. Chlormethiazole (1 mmol/kg) was administered intraperitoneally either 1 or 3 h after occlusion of the middle cerebral artery with an intraluminal filament. Twenty four hours after the start of occlusion there was(More)
The monofilament technique of transient middle cerebral artery occlusion (MCAO) was used in 3 separate studies to evaluate the efficacy of the low-affinity, use-dependent N-methyl-d-aspartate receptor antagonist, AR-R15896AR. First, a dose-response curve was attempted. Wister Kyoto rats received 2 hours of MCAO. Five minutes later, a 30-minute intravenous(More)