The protective action of nefiracetam against electrophysiological and metabolic damage in the hippocampus after deprivation of glucose and oxygen.
The present study examined the effect of nefiracetam on ischemic brain damage by monitoring population spikes (PSs) in the dentate gyrus of guinea pig hippocampal slices; assaying high-energy phosphates (ATP and CrP) in guinea pig hippocampal slices; and monitoring whole-cell membrane-currents and intracellular Ca(2+) levels in cultured hippocampal neurons. Twenty-minute ischemic insult to slices, i.e., deprivation of glucose and oxygen from artificial cerebrospinal fluid, abolished PSs. As compared with only 35% recovery of the PS amplitude for control, PS amplitude reversed to 65% of basal levels 40 min after returning normal conditions by treatment with nefiracetam (0.01 microM). Ischemic insult reduced the levels of adenosine triphosphate (ATP) and creatine phosphate (CrP) in slices, and when returned to normal conditions, recovering to 70 and 85% of basal values, respectively, 30 min after returning normal conditions. Nefiracetam (0.01 microM) facilitated the recovery of ATP and CrP, reaching 110 and 140% of basal values, respectively. Nefiracetam inhibited N-methyl-D-aspartate (NMDA)-evoked currents to 35% of basal amplitudes. Likewise, nefiracetam (0.01 microM) inhibited intracellular Ca(2+) rise through NMDA receptor channels to 30% of basal levels. The results of the present study, thus, suggest that nefiracetam has the potential to protect against ischemic brain damage, possibly in part by preventing from accumulation of intracellular calcium through NMDA receptor channels.
Aihara
H
H
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Li
X
X
Fujiwara
S
S
Matsumura
T
T
Okumura
S
S
Tozaki
H
H
Kanno
T
T
Ohta
K
K
Nagai
K
K
Nishizaki
T
T
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007003:Hypoglycemia / Q000378:metabolism / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010725:Phosphocreatine / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D018696:Neuroprotective Agents; D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D010725:Phosphocreatine; C058876:nefiracetam; D000244:Adenosine Diphosphate; D005947:Glucose; D002118:Calcium