Joan M. Fischer

Permeability of Different Experimental Brain Tumor Models to Horseradish Peroxidase

The permeability of different brain tumor models to horseradish peroxidase (HRP) was examined by determining the fraction of tumor that contained HRP after intravenous administration. The intracerebral tumor models studied were Avian Sarcoma Virus (ASV)-induced tumors and tumors from transplanted RG-2, S69-C1-5, and 9L cell lines. The average fraction of RG-2 tumors permeable to HRP was .95; of S69-C1-5 tumors, .699; of ASV-induced tumors, .63; and of 9L tumors, .52. Except for the RG-2 tumors, there was considerable regional variation in HRP permeability, which was most marked in the ASV-induced tumors. In ASV-induced tumors, HRP permeability did not correlate with tumor histo ogical classification, size, or anatomic location within the brain. The subcutaneous tumor models studied were RG-2-, S69-C1-5, and 9L-transplanted tumors in rats, and human glioblastoma cell lines transplanted into nude mice. All were completely permeable to HRP. These results indicate that significant differences in permeability to HRP exist among brain tumor models when the tumors are intracerebral, and that all subcutaneous tumors from transplanted glial cell lines are completely permeable to HRP. These variables must be considered in future studies of permeability in experimental brain tumors. Care must be exercised in extrapolating results about permeability from one brain tumor model to another

Regional cerebral blood flow in the beagle puppy model of neonatal intraventricular hemorrhage Studies during systemic hypertension

The newborn beagle puppy serves as an animal model for intraventricular hemorrhage (IVH) of the premature infant. Since increased systemic blood pressure has been implicated in the genesis of IVH in both babies and puppies, we studied regional cerebral blood flow in control and hypertensive puppies. Hypertension significantly increased blood flow to all structures. The largest increases occurred in gray matter, especially deep cerebral and brainstem nuclei. Blood flow also increased to deep hemispheric white matter, but the magnitude of the increase was smaller. Hypertension also increased blood flow to the subependymal germinal matrix (GM). The magnitude of the increase to most of the GM was small and similar to deep hemispheric white matter. The increase to the most rostral GM was higher and equal to the mean increase seen in gray matter. This rostralcaudal gradient of hypertension-induced hyperperfusion may explain the tendency for IVH to occur in rostral GM in premature babies. However, the failure to find a disproportionate increase in blood flow to GM during hypertension implies that additional factors besides hypertension-induced GM hyperperfusion may be involved in the pathogenesis of IVH.

Regional Cerebral Blood Flow in the Newborn Beagle Pup: the Germinal Matrix is a “Low-Flow” Structure

Summary: The newborn beagle pup serves as a model for neonatal intraventricular hemorrhage (IVH). Fluctuations in germinal matrix blood flow are felt to play a major role in the pathogenesis of IVH. We studied regional cerebral blood flow in awake newborn beagle pups utilizing [14C]-iodoantipyrine as a blood flow indicator and quantitative autoradiography. The equilibrium [tissue]:[blood] partition coefficient for iodoantipyrine was 1.13 ± .06 for grey matter. Blood flow was calculated for cerebral cortex (frontal = 59 ± 9 ml/100 g/min), 14 subcortical nuclear structures (e.g., caudate = 45 ± 6 ml/100 g/min), 3 white matter structures (centrum semiovale = 7 ± 1 ml/100 g/min), and germinal matrix (7 ± 1 ml/100 g/min) (mean ± S.E.).We conclude that under normal physiologic conditions the germinal matrix receives relatively low blood flow. This information can be used for comparison with germinal matrix blood flow during adverse experimental conditions.Speculation: wLow baseline blood flow may place the germinal matrix at risk for ischemic injury during hypoxic or hypotensive stress. This ischemic injury may be a critical step in the pathogenesis of intraventricular hemorrhage, either by disrupting vascular integrity or by producing a disproportionate increase in germinal matrix blood flow (luxury perfusion) after reestablishment of normoxemia and normotension.

Computed tomography of virally induced canine brain tumors: a preliminary report.

Seven neonatal dogs were inoculated intracerebrally with Avian Sarcoma Virus (ASV) and studied by computed tomography (CT) for intracranial tumors. The tumor yield was five anaplastic astrocytomas and two sarcomas, with an average latency of 57 days. Computed tomography accurately detected all tumors over 5 mm in diameter and predicted the size of the tumors within 3 mm. The intensity of contrast enhancement was directly related to the dose of Conray-60°. The area of enhancement on the CT scan correlated precisely with tumor permeability as determined histologically with horseradish peroxidase (HRP). Edema seen in CT scans correlated well with edema present in histological sections. Peritumoral edema was impermeable to both Conray-60° and HRP. The ASV-induced canine brain tumor model appears well suited for future CT studies.

Experimental gliomas An autoradiographic study of the endothelial component

Autochthonous gliomas were induced in rats by intracerebral inoculation of avian sarcoma virus and studied by 3H-thymidine autoradiography. Parenchymal glial tumor cells had a 3H-labeling index (LI) of 3.0 to 13.6%. Endothelial cells in tumor blood vessels had an LI of 2.6 to 34.3%, independent of and in most instances higher than the LI of the glial tumor. Endothelial cells of normal blood vessels had an average LI of 0.3%. This study documents the high proliferative rate of the endothelial cells in anaplastic experimental gliomas, and emphasizes the necessity for seeking direct, incontrovertible evidence to determine whether or not the rapidly proliferating endothelial cells are malignant.