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W H Marcussen

Publications and source records attributed to W H Marcussen.

7 recordsLinked to original sources
PubMed1989

Systemic carbachol used in radiation-controlled focal brain pharmacology can decrease rat running.

Radiation-controlled focal brain pharmacology is a method to concentrate a neuropharmacologic agent in any selected portion of the brain by irradiating that selected area and thereby lowering the BBB in that area. Then, when a drug that does not cross the normal BBB is administered systemically, the drug will preferentially penetrate and act only in the selected part of the brain. Rats received 20 Gy to the brainstem and then were tested with normal 0.9% saline 1 ml/kg, GABA 400 mg/kg, taurine 200 mg/kg, carbachol 1 mg/kg, amphetamine 2 mg/kg, and bicuculline methiodide 27 mg/kg. Opening the BBB produced no change in the average amount of running following the injection of saline. With the BBB closed, carbachol, bicuculline methiodide and taurine produced no statistically significant effect compared to saline. Comparing the effects of a drug when the BBB is open to that of saline when the BBB is open showed no significant effect of bicuculline methiodide, taurine and GABA. Carbachol produced a 73% reduction, significant at p less than .0001. Comparing a drug when the BBB is open to the same drug when the BBB is closed showed no significant effect of bicuculline methiodide, taurine and GABA. Carbachol produced a 65% reduction, significant at p less than .001. This shows that radiation-controlled focal brain pharmacology with carbachol can decrease the complex behavior of running.

Animals↗
PubMed1986

The late effects of radiation on the blood brain barrier.

Rats were irradiated with 60 to 20 Gy in a single dose focussed to a volume of 0.5 cc in the center of the left hemisphere. Breakdown of the BBB was detected by the presence of spikes on EEG after subcutaneous injection of Bicuculline methiodide, and the presence of staining following Evans Blue dye injection. Breakdown of the BBB (mean and standard deviation) occurred in 38/46 of the 60 Gy rats at 98 +/- 16 days, 7/11 of the 50 Gy rats at 128 +/- 25 days, 11/18 of the 40 Gy rats at 162 +/- 3 days, 5/11 of the 30 Gy rats at 178 +/- 5 days and, 7/12 of the 20 Gy rats at 217 +/- 7 days post irradiation. This study suggests that endothelial damage could be the principle mechanism mediating the late radiation syndrome.

Animals↗
PubMedDate not supplied

Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy.

Focal epilepsy can be produced by a blood-brain barrier (BBB)-excluded systemic convulsant (penicillin, folic acid, etc.) in the presence of a focal BBB lesion. Bicuculline methiodide, a gamma-aminobutyric acid blocking epileptogen, crosses the normal BBB of rats poorly and produces no consistent abnormality behaviorally or on EEG at 36 mg/kg. When the BBB is opened in 0.25 ml of cortex by 6,000 rad of alpha particles, by a pin trauma lesion, or by a heat lesion, the rats are normal clinically and on EEG. When these lesioned rats are challenged with bicuculline methiodide, 36 mg/kg, an intense, highly localized epileptiform discharge results that begins approximately 20 min after injection and lasts 30-90 min. The plausibility and experimental utility of the BBB-epileptogen model of epilepsy are enhanced by these observations.

Animals↗
PubMedDate not supplied

Systemic focal epileptogenesis.

Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

Animals↗
PubMedDate not supplied

Pharmacological response of systemically derived focal epileptic lesions.

Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

Action Potentials↗