Hyperthermia can exacerbate the brain damage produced by
ischemia. In the present study, we investigated the effects of
hyperthermia before and during
ischemia-reperfusion on neuronal damage and glial changes in the gerbil hippocampus following
transient cerebral ischemia using
cresyl violet staining, NeuN immunohistochemistry and
Fluoro-Jade B histofluorescence staining. The animals were randomly assigned to 4 groups: (1)
sham-operated animals with normothermia (normothermia +
sham group); (2)
ischemia-operated animals with normothermia (normothermia +
ischemia group); (3)
sham-operated animals with
hyperthermia (
hyperthermia +
sham group); and (4)
ischemia-operated animals with
hyperthermia (
hyperthermia +
ischemia group).
Hyperthermia (39.5 ± 0.2°C) was induced by exposing the gerbils to a heating pad connected to a rectal thermistor for 30 min before and during
ischemia-reperfusion. In the normothermia+ischemia groups, a significant delayed neuronal death was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) 5 days after
ischemia-reperfusion. In the hyperthermia+ischemia groups, neuronal death in the SP of the CA1 occurred at 1 day post-
ischemia, and neuronal death was observed in the SP of the CA2/3 region at 2 days post-
ischemia. In addition, we examined activations of astrocytes and microglia using immunohistochemistry for anti-
glial fibrillary acidic protein (GFAP) and anti-ionized
calcium-binding adapter molecule 1 (Iba-1). GFAP-positive astrocytes and Iba-1-positive microglia in the ischemic hippocampus were activated much earlier and much more accelerated in the hyperthermia+ischemia groups than those in the normothermia+ischemia groups. Based on our findings, we suggest that an experimentally hyperthermic pre-condition before cerebral ischemic insult produces more extensive neuronal damage and glial activation in the ischemic hippocampus.