Dexmedetomidine Pretreatment of Neuronal Cells Has Protective Effect Against Cell Death During Oxygen-glucose Deprivation/Reoxygenation, Based on IGF-1 Production.

OBJECTIVE

Insulin-like growth factor 1 (IGF-1) protects neuronal-cell damage by ischemia. Although neuronal cells have been reported to produce IGF-1, the molecular mechanisms remains obscure. Dexmedetomidine (DEX) protects neuronal cells from ischemic damage. We investigated the involvement of IGF-1 in the effect of DEX pretreatment on neuronal ischemic damage using an mouse hippocampal neuron model.

MATERIALS

We used Dexmedetomidine and cryopreserved passaged mouse hippocampal neuronal HT22. Other reagents in this study were analytical grade.

METHODS

Ischemia-reperfusion was modeled using the oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of DEX was examined by incubating cells in DEX-containing medium for 1 hour prior to OGD/R. The cell damages were evaluated by lactate dehydrogenase (LDH) release. The amount of released IGF-1 were evaluated quantitatively by ELISA. The degree of Akt phosphorylation was evaluated by western blotting.

RESULTS

OGD/R loading promoted LDH release from neuronal cells, while DEX pretreatment suppressed the LDH release. IGF-1 release from them was primed by DEX pretreatment under OGD/R condition, but not under normal conditions. Akt was activated in DEX-pretreated cells following OGD/R loading. IGF-1 neutralizing antibody (IGF-1) eliminated the above effects of DEX pretreatment. However, IGF-1 receptor expression in neuronal cells was not affected by DEX pretreatment prior to OGD/R loading.

CONCLUSIONS

Our results demonstrate that neuronal cells primed with DEX under OGD/R conditions could release IGF-1 and potentially protect themselves via the IGF-1/Akt pathway. Consequently, it appears that neuronal cells activated by DEX have the capacity to self-protect from ischemic damage.