Effects of an interleukin-1 β analogue [Lys- d-Pro-Thr], on incomplete cerebral ischemia-induced inhibition of long-term potentiation in rat hippocampal neurons in vivo

Although interleukin-1 β (IL-1 β) has recently been implicated in neuronal cell death in vitro and in vivo after global forebrain ischemia, the role of IL-1 β in the functional injuries, i.e. impairment of synaptic transmission, after cerebral ischemia that does not cause neuronal death in the nervous system remains unknown. To address this question, we investigated the effect of short-term incomplete ischemia without apparent neural death on hippocampal long-term potentiation (LTP) in anesthetized rats, and examined the possible role of IL-1 β as an intermediary in this effect. Short-term incomplete cerebral ischemia (10 min) was induced in halothane-anesthetized rats by bilaterally clamping the common carotid arteries. Four days after ischemia, functional injuries in neuronal transmission in the hippocampal formation were observed without significant changes in pathological studies such as neuronal cell death. The LTP elicited in both Shaffer-CA1 synapses and perforant path-dentate gyrus synapses was significantly inhibited by the short-term incomplete ischemia. This inhibition of LTP was blocked by IL-1 β tripeptide antagonist (Lys- d-Pro-Thr), suggesting that the inhibitory effect of mild ischemia on synaptic potentials and LTP may be mediated by the generation of IL-1 β. These findings have important implications for the role of IL-1 β in not only neuronal cell death but also functional injuries without cell loss, perhaps elicited by transient cerebral ischemia.