Neuronal injury remains a leading cause of morbidity in both neonates and adults with injuries induced by intracranial hemorrhage, ischemia–reperfusion, and excitotoxicity. To date, a number of neuroprotective strategies have been evaluated, but they have shown little benefit. Poloxamer 188 (P-188), a membrane-active triblock copolymer, has been studied extensively as a cell-membrane sealant. The authors used an animal model to study the neuroprotectant effects of P-188 administered by intracisternal (IC) injection after experimentally induced intraparenchymal hemorrhage.
Sprague–Dawley rats received an IC injection of either P-188 or vehicle (artificial cerebrospinal fluid) 10 minutes after striatal infusion of 50 μl of autologous blood. Animals from both treatment groups were killed either 2 or 7 days later. In a second experiment, after striatal blood infusion and early IC injection of either P-188 or vehicle, animals received daily IC injections of either P-188 or vehicle for 5 days, and were killed 7 days after induction of the experimental hemorrhage. Striatal tissues were histologically analyzed for neuronal loss, and lesion volumes were determined.
Lesion volumes in the animals that received a single dose of P-188 were significantly smaller (mean ± standard deviation 18.3 ± 4.3 mm3, six rats; p = 0.04) than those in the control group (31.4 ± 4.3 mm3, seven rats) when measured 2 days postinjection; however, no difference in lesion volumes was present 7 days postinjection. Lesion volumes in the animals who received 5 days of daily P-188 injections were significantly smaller (1.50 ± 0.58 mm3, 10 rats; p = 0.04) than those in the corresponding control group (5.04 ± 1.85 mm3, eight rats) when measured at 7 days.
A single dose of P-188 protects against early neuronal loss after hemorrhage but has no effect on long-term hemorrhage-induced neuronal loss. However, repeated daily P-188 treatment appears to produce effective long-term neuronal protection.