Talampanel, a novel noncompetitive AMPA antagonist, is neuroprotective after traumatic brain injury in rats.
J Neurotrauma
; 18(10): 1031-8, 2001 Oct.
Article
em En
| MEDLINE
| ID: mdl-11686490
ABSTRACT
Talampanel [(R)-7-acetyl-5-(4-aminophenyl)-8,9-dihydro-8-methyl-7H-1,3-dioxolo[4,5-h][2,3] benzodiazepine] is an orally active noncompetitive antagonist of the AMPA subtype of glutamate excitatory amino acid receptors. The purpose of this study was to determine whether treatment with talampanel would protect in a rat model of traumatic brain injury (TBI). Twenty-four hours prior to TBI, a fluid-percussion interface was positioned parasagittally over the right cerebral cortex. On the following day, fasted rats were anesthetized with 3% halothane, 70% nitrous oxide, and a balance of oxygen; mechanically ventilated and physiologically regulated; and subjected to right parieto-occipital parasagittal fluid-percussion injury (1.5-2.0 atm). The agent (talampanel, bolus infusion of 4 mg/kg followed by infusion of 4 mg/kg/h over 72 h) or vehicle was administered i.v. starting at either 30 min or 3 h after trauma. Seven days after TBI, brains were perfusion-fixed, coronal sections at various levels were digitized, and contusion areas were measured. Treatment with talampanel, when instituted 30 min after trauma, significantly reduced total contusion area compared to vehicle-treated rats (0.54 +/- 0.25 vs. 1.79 +/- 0.42 mm2, respectively). When talampanel treatment was begun at 3 h, the neuroprotective effect of the drug was lost. In addition, treatment with talampanel starting at 30 min significantly attenuated neuronal damage in all three subsectors of the hippocampal CA1 sector compared to vehicle-treated rats (normal-neuron counts, right (ipsilateral) medial CA1 80.3 +/- 2.0 [talampanel] vs. 66.3 +/- 2.1 [vehicle] (mean +/- SEM); middle CA1 71.5 +/- 2.0 vs. 60.3 +/- 2.2; lateral CA1 74.5 +/- 3.0 vs. 63.0 +/- 3.2, respectively). By contrast, when talampanel treatment was begun at 3 h, normal pyramidal-neuron counts were almost identical in both groups. Our findings document that talampanel therapy instituted 30 min after trauma significantly reduces histological damage.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Receptores de AMPA
/
Fármacos Neuroprotetores
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Neurotrauma
Assunto da revista:
NEUROLOGIA
/
TRAUMATOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos