Pyramidal neurons in region I of hippocampus proper (CA1) are particularly vulnerable to excitotoxic processes following transient forebrain
ischemia.
Kynurenic acid (KYNA) is a small molecule derived from
tryptophan when this
amino acid is metabolized through the
kynurenine pathway. In the present study, we examined the effects of ischemic preconditioning (IPC) on the immunoreactivity and
protein levels of KYNA following 5 min of transient forebrain
ischemia in gerbils. The animals were randomly assigned to 4 groups (
sham-operated group,
ischemia-operated group, IPC +
sham-operated group and IPC +
ischemia-operated group). IPC was induced by subjecting the gerbils to 2 min of
ischemia followed by 1 day of recovery. In the
ischemia-operated group, we observed a significant loss of pyramidal neurons in the CA1 stratum pyramidale (SP) at 5 days post-
ischemia; however, in the IPC +
ischemia-operated group, the pyramidal neurons were well protected. KYNA immunoreactivity in the SP of the
ischemia-operated group was significantly altered following
ischemia-reperfusion and was very low 5 days following
ischemia-reperfusion. In the IPC +
ischemia-operated group, however, KYNA immunoreactivity was constitutively detected in the SP of the CA1 region after the ischemic insult. We also found that the alteration pattern of the KYNA
protein level in the CA1 region following
ischemia was generally similar to the immunohistochemical changes observed. In brief, our findings demonstrated that IPC maintained and even increased KYNA immunoreactivity in the SP of the CA1 region following
ischemia-reperfusion. The data from the present study thus indicate that the enhancement of KYNA expression by IPC may be necessary for neuronal survival following transient ischemic injury.