1 We examined the eect of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (ibudilast), which has been clinically used for bronchial asthma and cerebrovascular disorders, on cell viability induced in a model of reperfusion injury. 2 Ibudilast at 10 ± 100 mM signi®cantly attenuated the H 2 O 2 -induced decrease in cell viability. 3 Ibudilast inhibited the H 2 O 2 -induced cytochrome c release, caspase-3 activation, DNA ladder formation and nuclear condensation, suggesting its anti-apoptotic eect. 4 Phosphodiesterase inhibitors such as theophylline, pentoxyfylline, vinpocetine, dipyridamole and zaprinast, which increased the guanosine-3',5'-cyclic monophosphate (cyclic GMP) level, and dibutyryl cyclic GMP attenuated the H 2 O 2 -induced injury in astrocytes. 5 Ibudilast increased the cyclic GMP level in astrocytes. 6 The cyclic GMP-dependent protein kinase inhibitor KT5823 blocked the protective eects of ibudilast and dipyridamole on the H 2 O 2 -induced decrease in cell viability, while the cyclic AMPdependent protein kinase inhibitor KT5720, the cyclic AMP antagonist Rp-cyclic AMPS, the mitogen-activated protein/extracellular signal-regulated kinase inhibitor PD98059 and the leukotriene D 4 antagonist LY 171883 did not. 7 KT5823 also blocked the eect of ibudilast on the H 2 O 2 -induced cytochrome c release and caspase-3-like protease activation. 8 These ®ndings suggest that ibudilast prevents the H 2 O 2 -induced delayed apoptosis of astrocytes via a cyclic GMP, but not cyclic AMP, signalling pathway.

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