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Daniel J Curry

Publications and source records attributed to Daniel J Curry.

7 recordsLinked to original sources
PubMed2007

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

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.

Animals↗
PubMed2004

The surfactant poloxamer-188 protects against glutamate toxicity in the rat brain.

Membrane repair of damaged neurons by surfactant poloxamers has been noted in experimental spinal cord injury and in vitro excitotoxicity. We examined poloxamer-188 (P-188)-mediated neuroprotection in a rat model of glutamate toxicity. Quinolinate was infused into the striatum followed 10 min and 4 h later by P-188 administered either i.v. or intracisternally (i.c.), or by vehicle. Mean neuronal loss examined volumetrically 7 days later in control animals was 50% greater (P < 0.01) than after i.c. P-188 treatment; control lesion volumes were 38% greater than lesion volumes after i.v. P-188 treatment; however, that comparison did not reach significance. This robust protection against glutamate toxicity may predict P-188-mediated neuroprotection against a broad range of clinically relevant neural insults.

Animals↗
PubMed2004

Poloxamer 188 volumetrically decreases neuronal loss in the rat in a time-dependent manner.

OBJECTIVE: Excitotoxicity is a multistep process that results in either necrosis or apoptosis. It has been associated with neuronal death in trauma, ischemia, and neurodegeneration. The final step in necrotic cell death is the rupture of a cell's plasma membrane; repair of this membrane rupture is a potentially powerful technique of neuroprotection. Poloxamer 188 (P-188) is a synthetic surfactant that seals experimentally porated membranes. This study investigated the usefulness and time dependence of intrathecal P-188 in protecting neurons in an in vivo model of excitotoxicity in the rat. METHODS: Twenty-eight Sprague-Dawley rats underwent striatal infusion of quinolinic acid to produce a spherical excitotoxic lesion. Each animal then received either vehicle or P-188 at 10 minutes, 4 hours, or both time points after surgery by direct cisterna magna injection. Animals were killed at 1 week, and brains were stained immunohistochemically for the neuronal marker Neu-N. Volumes of neuronal loss were calculated and compared between groups by analysis of variance. RESULTS: All animals were found to have spherical, stereotyped lesions. The animals that received intrathecal poloxamer at the early injection time had statistically smaller lesions (8.16 +/- 6.12 mm(3); n = 5; P = 0.0015) than controls (18.25 +/- 11.42 mm(3); n = 11). Those animals that received poloxamer at both injection times also had statistically smaller lesions (10.57 +/- 9.00 mm(3); n = 7; P = 0.0095). The group that received poloxamer at the late injection time only did not have significantly decreased lesion size (14.86 +/- 7.95 mm(3); n = 5). CONCLUSION: Intrathecal P-188 reduces neuronal loss after excitotoxic injury in the rat only when delivered immediately after the toxin. This observation confirms the potential of surfactant molecules as neuroprotectants but predicts that their usefulness is best realized by early and potentially ongoing treatment.

Animals↗
PubMed2004

Magnesium and experimental vasospasm.

OBJECT: Interest has developed in the use of magnesium (Mg++) as a neuroprotectant and antivasospastic agent. Magnesium may increase cerebral blood flow (CBF) and reduce the contraction of cerebral arteries caused by various stimuli. In this study the authors tested the hypothesis that a continuous intravenous infusion of Mg++ reduces cerebral vasospasm after experimental subarachnoid hemorrhage (SAH). METHODS: A dose-finding study was conducted in five monkeys (Macaca fascicularis) to determine what doses of intravenous MgSO4 elevate the cerebrospinal fluid (CSF) concentrations of Mg++ to vasoactive levels and to determine what effects these doses have on the diameters of cerebral arteries, as shown angiographically. After a standard dose of MgSO4 had been selected it was then administered in a randomized, controlled, blinded study to 10 monkeys (five animals/group) with SAH, beginning on Day 0 and continuing for 7 days, at which time angiography was repeated. A 0.086-g/kg bolus of MgSO4 followed by an infusion of 0.028 g/kg/day MgSO4 significantly elevated serum and CSF levels of Mg++ (five monkeys). Magnesium sulfate significantly elevated the serum level of total Mg++ from a control value of 0.83 +/- 0.04 mmol/L to 2.42 +/- 1.01 mmol/L on Day 7 and raised the CSF level from 1.3 +/- 0.04 mmol/L to 1.76 +/- 0.14 mmol/L. There was no angiographic evidence of any effect of MgSO4 on normal cerebral arteries. After SAH, the vasospasm in the middle cerebral artery was not significantly reduced (46 +/- 8% in the MgSO4-treated group compared with 35 +/- 6% in the placebo [vehicle]-treated group, p > 0.05, unpaired t-test). CONCLUSIONS: Magnesium sulfate did not significantly reduce cerebral vasospasm after SAH in the doses tested. An investigation of SAH is warranted mainly to test whether a benefit can be achieved by neuroprotection or by augmentation of CBF by dilation of small vessels and/or collateral pathways.

Animals↗
PubMed2004

Surfactant poloxamer 188-related decreases in inflammation and tissue damage after experimental brain injury in rats.

OBJECT: The surfactant, poloxamer 188 (P-188), has been found to protect against tissue injury in various experimental models. Its protective mechanism may involve the effects of the surfactant against oxidative stress and inflammation. The authors investigated the role of P- 188 in the reduction of tissue injury and macrophage response in a model of excitotoxic brain injury in the rat striatum. METHODS: Fifteen Sprague-Dawley rats underwent stereotactic injection of 120 nmol of quinolinic acid into the striatum and received intracisternal injection of vehicle or P-188 (40 mg/kg) at 10 minutes and 4 hours postinjury. Rats were killed after 1 week, and the histological score was determined based on the degree of overall tissue injury (Grades 1-4) at the lesion site. The number of macrophages within the lesioned striatum was compared with that found within the striatum on the nonoperated contralateral side. The scores related to tissue damage and the macrophage ratios of each group were then compared using t-tests. Striatal injection of the toxin produced a lesion characterized by necrosis and inflammation surrounding the injection site in all six control animals. In rats in which intracisternal P-188 was administered, significantly less tissue injury was demonstrated (mean score 2.45 +/- 0.74) than in controls (mean score 3.14 +/- 0.75) (p = 0.045). The rats that received intracisternal surfactant also had significantly less macrophage infiltrate (mean ratio 1.06 +/- 0.18) than control animals (mean ratio 2.00 +/- 0.48) (p = 0.004). CONCLUSIONS: The surfactant P-188 reduces tissue loss and macrophage infiltrate after excitotoxic brain injury in the rat. Possible mechanisms of this effect may include direct surfactant modulation of inflammatory cell membrane fluidity.

Animals↗
PubMedDate not supplied

Endoscopic, single-catheter treatment of Dandy-Walker syndrome hydrocephalus: technical case report and review of treatment options.

Optimal treatment for hydrocephalus related to Dandy-Walker syndrome (DWS) remains elusive. Patients with DWS-related hydrocephalus often require combinations of shunting systems to effectively drain both the supratentorial ventricles and posterior fossa cyst. We describe an endoscopic technique, whereby a frontally placed, single-catheter shunting system effectively drained the supratentorial and infratentorial compartments. This reduces the complexity and potential risk associated with the combined shunting systems required by so many with DWS-related hydrocephalus.

Catheterization↗