Impact of hyperthermia before and during ischemia reperfusion on neuronal damage and gliosis in the gerbil hippocampus induced by transient cerebral ischemia

Introduction

Hyperthermia can exacerbate the brain damage produced by ischemia. In the present study, we investigated 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.

Methods

The animals were randomly assigned to four groups: sham-operated animals with normothermia (normothermia + sham group); ischemia-operated animals with normothermia (normothermia + ischemia group); sham-operated animals with hyperthermia (hyperthermia + sham group); and 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 minutes before and during ischemia-reperfusion.

Results

In the normothermia + ischemia group, 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 group, 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 activation 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 group than those in the normothermia + ischemia group.

Conclusion

Based on our findings, we suggest that experimentally hyperthermic precondition before cerebral ischemic insult produces more extensive neuronal damage and glial activation in the ischemic hippocampus.