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- W1990333518 abstract "Experimental preconditioning provides beneficial outcomes in conditions such as cardiac surgery, brain surgery and stroke. Here we evaluated the protective effects of low-dose subcutaneous GYKI-52466 preconditioning in a rat model of hypoxic–ischaemic (HI) brain injury. Male Sprague–Dawley rats (postnatal day 26) were administered saline or GYKI-52466 (GYKI; 3-mg/kg, 90 min; 1-mg/kg, twice in 120 min; or 0.5-mg/kg, thrice in 180 min) prior to left common carotid artery occlusion. Animals were allowed to recover for 2 h, and then placed in a hypoxia chamber (8% O2/92% N2; 33 ± 1°C) for 1 h. A sham surgery group received saline without HI. Seizure activity was scored during hypoxia and sensorimotor tests performed before surgery and at 1, 7, 14 and 90 days post-HI. On days 14 and 90 brains were fixed and sectioned for the assessment of infarct size and ventricular enlargement. Low-dose GYKI-52466 preconditioning significantly reduced infarct volume and ventricular enlargement relative to saline-treated controls at day 14 after HI. On day 90, tissue loss was significantly reduced by GYKI 3-mg/kg compared to saline. Foot-faults, paw use asymmetry, and postural reflex scores were significantly improved in all GYKI treatment groups. Our results show that GYKI-52466 is effective at doses well-below, and at pre-administration intervals well-beyond previous studies, and suggest that a classical blockade of ionotropic AMPA receptors does not underlie its neuroprotective effects. Low-dose GYKI-52466 preconditioning represents a novel, prophylactic strategy for neuroprotection in a field almost devoid of effective pharmaceuticals." @default.
- W1990333518 created "2016-06-24" @default.
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- W1990333518 date "2013-03-01" @default.
- W1990333518 modified "2023-09-26" @default.
- W1990333518 title "Low-dose GYKI-52466: Prophylactic preconditioning confers long-term neuroprotection and functional recovery following hypoxic–ischaemic brain injury" @default.
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- W1990333518 doi "https://doi.org/10.1016/j.neuroscience.2012.11.063" @default.
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