Chemical preconditioning with 3-nitropropionic acid in gerbil hippocampal slices: therapeutic window and the participation of adenosine receptor.
Ischemic tolerance induced by a subtoxic dose of neurotoxin, 3-nitropropionic acid (3-NPA), was recently reported as "chemical preconditioning." We electrophysiologically investigated the therapeutic window and the effect via action at the adenosine receptor using a gerbil hippocampal slice model of the tolerance phenomenon. 3-NPA at the dose of 4 mg/kg was administered intraperitoneally at 3, 24, and 72 h prior to slice preparation. Prolonged delay to hypoxic depolarization (HD) and improvement of the field excitatory postsynaptic potential recovery following a fixed period of hypoxia (8 min) were observed in the groups pretreated at 3 and 24 h compared with the control (P < 0.05). Correlation between the delay to HD and the recovery was highly significant (r = 0.37, P < 0.001). These effects were completely reversed by administration of theophylline (20 mg/kg), an adenosine receptor blocker. These findings indicate that chemical preconditioning with 3-NPA induces early onset (3 h) and long-lasting (24 h) tolerance of hypoxic damage to excitatory synaptic mechanisms in the hippocampus by delayed calcium entry, and the activation of adenosine receptor contributes to this neuroprotective effect.
Aketa
S
S
Department of Neurosurgery, Nara Medical University, Nara, Japan.
Nakase
H
H
Kamada
Y
Y
Hiramatsu
K
K
Sakaki
T
T
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism; D019194:Ischemic Preconditioning; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009574:Nitro Compounds; D009924:Organ Culture Techniques; D011422:Propionates / Q000494:pharmacology*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D013806:Theophylline; C015392:3-nitropropionic acid