Isoflurane postconditioning improved long-term neurological outcome possibly via inhibiting the mitochondrial permeability transition pore in neonatal rats after brain hypoxia-ischemia.

BACKGROUND

Isoflurane postconditioning induces neuroprotection in neonatal rats after hypoxia/ischemia (HI). Here, we evaluated the possible role of inhibiting the mitochondrial permeability transition pore (mPTP) in isoflurane postconditioning-improved long-term neurological outcome after brain HI.

METHODS

Seven-day-old Sprague-Dawley rats (n=360) were randomly divided into eight groups (n=45 in each). They underwent or did not undergo left common carotid arterial ligation followed by exposure to 8% oxygen for 2 h at 37°C (brain HI). The mPTP opener atractyloside or inhibitor cyclosporin A was injected into the lateral cerebral ventricle. The weight ratio and neuronal density ratio in the ventral posteromedial thalamic nucleus and hippocampal CA3 area of left to right cerebral hemispheres were evaluated at 7 or 35 days after brain HI. The changes of mitochondrial optical density (ΔOD540 of mPTP) and the performance in Morris water maze were assessed.

RESULTS

Compared with the control (sham group), brain HI decreased the weight ratio and neuronal density ratio in the ventral posteromedial thalamic nucleus and hippocampal CA3 area (P<0.05). Brain HI also impaired the performance of rats in the Morris water maze and increased the ΔOD540. These effects of brain HI were reduced by isoflurane postconditioning and cyclosporin A. The improvement induced by isoflurane postconditioning was attenuated by atractyloside.

CONCLUSIONS

Isoflurane postconditioning improved long-term neurological functions after brain HI in neonatal rats. Inhibiting the opening of the mPTP may contribute to this protection.