Low-dose GYKI-52466: prophylactic preconditioning confers long-term neuroprotection and functional recovery following hypoxic-ischaemic brain injury.
Neuroscience
; 232: 128-38, 2013 Mar 01.
Article
en En
| MEDLINE
| ID: mdl-23246617
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 2h, and then placed in a hypoxia chamber (8% O2/92% N2; 33 ± 1°C) for 1h. 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benzodiazepinas
/
Fármacos Neuroprotectores
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Recuperación de la Función
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Hipoxia-Isquemia Encefálica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2013
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda
Pais de publicación:
Estados Unidos