Neuroprotective effect of the surfactant poloxamer 188 in a model of intracranial hemorrhage in rats

J Neurosurg. 2007 Jan;106(1 Suppl):36-40. doi: 10.3171/ped.2007.106.1.36.


Object: 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.

Methods: Sprague-Dawley rats received an IC injection of either P-188 or vehicle (artificial cerebrospinal fluid) 10 minutes after striatal infusion of 50 microl 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 mm(3), six rats; p = 0.04) than those in the control group (31.4+/-4.3 mm(3), 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 mm(3), 10 rats; p = 0.04) than those in the corresponding control group (5.04+/-1.85 mm(3), eight rats) when measured at 7 days.

Conclusions: 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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cerebral Hemorrhage, Traumatic / drug therapy*
  • Cerebral Hemorrhage, Traumatic / pathology
  • Cisterna Magna / pathology
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Injections, Intraventricular
  • Lipid Peroxidation / drug effects
  • Male
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Poloxamer / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Surface-Active Agents / pharmacology*
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / pathology


  • Neuroprotective Agents
  • Surface-Active Agents
  • Poloxamer