Neuroprotective effect of the surfactant poloxamer 188 in a model of intracranial hemorrhage in rats.
OBJECTIVE
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.
Cadichon
Sandra B
SB
Section of Neonatology, The University of Chicago, Chicago, Illinois 60637, USA.
Le Hoang
M
M
Wright
David A
DA
Curry
Daniel J
DJ
Kang
Un
U
Frim
David M
DM
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D020202:Cerebral Hemorrhage, Traumatic / Q000188:drug therapy* / Q000473:pathology; D002946:Cisterna Magna / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D020442:Poloxamer / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013501:Surface-Active Agents / Q000494:pharmacology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000473:pathology
D018696:Neuroprotective Agents; D013501:Surface-Active Agents; D020442:Poloxamer