Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia

• Published in: Pharmacological research 2002-04, Vol.45 (4), p.305-311
• Main Authors: Yoshioka, Mitsuhiro, Suda, Noriyuki, Mori, Kiyoshi, Ueno, Ken-ichi, Itoh, Yoshitada, Togashi, Hiroko, Matsumoto, Machiko
• Format: Article
• Language: English
• Subjects: Animals; Area Under Curve; Avoidance Learning - drug effects; Brain - pathology; cognition, long-term potentiation, cerebral ischemia; Dentate Gyrus - drug effects; Dentate Gyrus - pathology; Dentate Gyrus - physiology; Hippocampus - drug effects; Hippocampus - pathology; Hippocampus - physiology; Ischemic Attack, Transient - pathology; Ischemic Attack, Transient - psychology; Long-Term Potentiation - drug effects; Male; Pyridines - pharmacology; Rats; Rats, Wistar; Vasodilator Agents - pharmacology
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.2002.0949

The present study evaluated the effects of ibudilast on impaired passive avoidance responses and hippocampal long-term potentiation (LTP) caused by transient cerebral ischemia in rats. The hippocampal nerve cell density was also measured. The latency determined in retention trials of passive avoidance shortened significantly in the 4-vessel occlusion (4VO) group (in which four blood vessels were occluded for 20 min to cause cerebral ischemia). A significant recovery in the latency was observed by administration of ibudilast (10 mg kg −1). The population spike amplitude in both the hippocampal CA1 region and perforant path-dentate gyrus synapses was potentiated by tetanus stimulation in the sham-operated group, while in the 4VO group, LTP was significantly inhibited. This inhibition was reversed by administration of ibudilast (10 mg kg −1). A marked reduction of cell densities in the CA1 region was observed in the 4VO group compared with the normal group. The nerve cell density in the hippocampal CA1 region was decreased by 20 min of cerebral ischemia. Ibudilast significantly inhibited the reduction of cell densities in a dose-dependent manner. In contrast, the cell density in the dentate gyrus was comparable in the 4VO and normal groups, and no significant changes were observed in the ibudilast groups. These findings suggest that ibudilast might possess neuronally protective properties, i.e. protecting neurons not only from deaths but also from functional damage due to certain cerebral ischemia.