The effects of mannitol and hypothermia on spontaneous spreading depression induced by anoxia in the rat hippocampal CA1

There is evidence that strongly suggests spreading depression (SD) is an important factor in hypoxia/ischemia induced neural damage. Treatments that prevent the occurrence of SD may be useful in providing neuronal protection against hypoxia. Recently, we reported that thiopental could prevent the occurrence of SD during brief anoxia on rat hippocampal slice in vitro. Moreover, we investigated that SD occurred spontaneously without electric stimulation (SSD) in hippocampal slices. The current study was designed to determine whether thiopental (2 × 10^-4 M), mannitol (25, 50, 100 mM) and hypothermia (28, 32°C), which are known to induce prophylaxis against hypoxia, could inhibit the occurrence of SSD. The effects of anoxia (5 min) on the extracellularly recorded field potential of CA1 pyramidal neurons were assessed. Under control condition (37°C, no drug), the anoxia induced-SSD occurred in 89% of slices. Thiopental and hypothermia (28°C) significantly reduced AD to 44% and 17%, respectively, whereas mild-hypothermia (32°C) and mannitol had no effect. Pre-treatment of thiopental and severe-hypothermia reduced occurrence of the anoxia induced-SSD, suggesting the prophylactic effects against SSD during anoxia.