Heat shock pretreatment attenuates sepsis-associated encephalopathy in LPS-induced septic rats

Sepsis is the most common cause of mortality in intensive care units. Although sepsis-associated encephalopathy (SAE) is reported to be a leading manifestation of sepsis, its pathogenesis remains unclear. In our previous studies, we showed that heat shock pretreatment can reduce mortality in polymicrobial septic rats and protect the cerebral cortical function during hypoxia or drug-induced convulsion. In the present study, we investigated to what extent heat shock pretreatment might affect the development of SAE in septic rats and the possible mechanism behind its effect was discussed. To do this, we used lipopolysaccharide (LPS) to induce septic response in a SAE animal model. Heat shock pretreatment was performed and rectal temperature maintained between 41 and 42 °C for 15 min using an electric heating pad. Electroencephalography (EEG) activity, a sensitive electrophysiological recording of electrical activity in the brain, was used as an indicator of cerebral cortical dysfunction in SAE. In LPS rats not pretreated with heat shock, the EEG background activity decreased 10 min after intraperitoneal administration of LPS. However, in rats pretreated with heat shock, this decrease was significantly attenuated. Untreated septic rats were also found to have earlier, more frequent epileptic spikes. In summary, we found that heat shock could attenuate the electro-cortical dysfunction in rats with LPS-induced septic response, suggesting that heat shock response might potentially be used to prevent SAE in sepsis.