A new rat brain tumor model: Glioma disseminated via the cerebral spinal fluid pathways

Abstract

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 x 10(2) to 5 x 10(5)) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible and dependent upon the number of cells injected. The median survival of three groups of rats receiving 5 x 10(5) cells in three different experiments was 17, 18 and 19 days respectively. For three groups receiving 5 x 10(4) cells, the median survival was 23, 24 and 25.5 days respectively and for two groups receiving 5 x 10(3) cells the median survival was 28 and 30 days respectively. The animals developed multiple tumor implants along the CSF pathways usually resulting in hydrocephalus. This tumor model was developed to simulate dissemination via CSF pathways as seen with medulloblastoma and other primitive neuroectodermal tumors of the central nervous system. It will be used to evaluate the therapeutic efficacy of intraventricularly administered anti-neoplastic drugs against small implants and malignant cells in the CSF pathways.

Animal models of tumour-associated epilepsy

“…In most cases, if not sacrificed before, or treated with cytostatic interventions, all animals die within approx. 30-35 days, with a 50% survival of 16-25 days (Aas et al, 1995;Beaumont et al, 1996;Desmarais et al, 2012;Krajewski et al, 1986;Rewers et al, 1990;Stafford et al, 2010;Scheck et al, 2012), and own unpublished observations in the course of pilot experiments to glioma-implantation studies Senner et al, Q6 2004). This somehow matches the clinical course of high-grade gliomas e.g.…”

“…The reason for this may be that the authors (often concentrating on oncological aspects) did not look for such signs, and indeed overlooked them since in many cases, even if seizure-like activity is being observed in the EEG, behavioural signs are often quite subtle, comprising freezing, facial automatisms and head tremor, or massive startle response in reaction to audiogenic stimuli, and only very seldom generalised tonic-clonic convulsions (Buckingham et al, 2011;Campbell et al, 2015;Köhling et al, 2006). Another reason may be that tumour cell injection into areas other than the neocortex such as capsula interna, corpus striatum or even cerebellar subdural space, are probably not ideal for the purpose of an epilepsy model (Aas et al, 1995;Beaumont et al, 1996;Hossmann et al, 1989;Krajewski et al, 1986;Linn et al, 1989;Rewers et al, 1990;Wechsler et al, 1989). Another problem is also revealed in Table 1.…”

lacZ Transduction of 9L Rat Tumor Cells without Cloning

“…Rats were anesthetized with Metofane (Pitman Moore, Chi cago, 111., USA), and a volume of 10 pi containing TumorBiol 1997;18:321-3315 x 104 cells was stercotactically injected into the cau date nucleus of Fisher 344 rats weighing 180-200 g. Rats were euthanized when they showed signs of tumor growth, and samples were collected. The meth od of tumor cell implantation was as described pre viously [13]. In accordance with animal welfare re quirements, rats with implanted tumor were killed when they lost more than 20% o f their body weight or showed overt signs of tumor growth, including loss of reflexes, failure to cat or drink for 2 days or porphyrin accumulations around the eyes.…”

“…Colony-forming efficiency (CFE) assay as a test of survival of cells with proliferative capacity was done as previously described [13]. Briefly, after different doses of radiation provided by an external 137Cs source (Shepherd, San Fernando, Calif, USA) or after treat ment with different doses of [3H] thymidine, cells were assessed for their colony-forming ability.…”

“…The method of culturing and handling 9L gliosarcoma cells has been described in detail previously [13][14][15]. Briefly, mycoplasma-free 9L rat gliosarcoma cells were stored in liquid nitrogen at a given passage, and every 3 months, an aliquot was thawed and tested before use in experiments.…”