Low-dose but not high-dose prostaglandin E1 improves the histological outcome of severe forebrain ischemia in rats

Prostaglandin E-1 (PGE(1)) has been shown to provide short-term neuroprotection against various types of brain ischemia in a dose-dependent manner in mice. However, these findings were obtained from experiments performed without any control over physiological parameters. We performed an outcome study where physiological parameters were controlled in an attempt to confirm the dose-dependant neuroprotective effects of PGE(1). A rat model of severe forebrain ischemia was used. Two doses of PGE(1) were administered during the pre-ischemic period, a low dose (LowPG group) and a high dose (HighPG group). Normotension was maintained in the LowPG group, while hypotension was induced in the HighPG group. In separate groups, normal saline (Control) or sodium nitroprusside (SNP) were infused to compare outcomes under similar blood pressure conditions. Histological outcomes in the hippocampal CA1 and entorhinal cortex were evaluated 5 days post-ischemia. HighPG resulted in hyperglycemia. The percentage of dead neurons in the hippocampal CA1 and entorhinal cortex were similar in the Control, SNP, and HighPG groups, the percentage being significantly attenuated in the LowPG group (CA1: Control = 92.8 +/- A 2.4%, LowPG = 85.0 +/- A 8.5%, HighPG = 95.3 +/- A 2.4%, and SNP = 96.4 +/- A 0.7%, P < 0.01; entorhinal cortex: Control = 73.8 +/- A 4.0%, LowPG = 53.2 +/- A 12.3%, HighPG = 72.1 +/- A 12.6%, and SNP = 76.5 +/- A 4.1%, P < 0.01). Pre-ischemic administration of low-dose PGE(1) in rats provided neuroprotection against severe forebrain ischemia. A dose dependency was not observed with PGE(1) dose and outcome.