Comparative Medicine - LABSG



Comparative Medicine

Volume 65, Number 1, February 2015

ORIGINAL RESEARCH

Mouse Models

Henderson et al. A Comparison of Mouse Parvovirus 1 Infection in BALB/c and C57BL/6 Mice:  Susceptibility, Replication, Shedding, and Seroconversion, pp. 5-14

Primary Species: Mouse (Mus musculus)

Domain 1

 

SUMMARY: According to the article, mouse parvovirus 1 (MPV1) is the most common parvovirus of laboratory mice.   Although MPV1, unlike mouse minute virus (MMV), has not been shown to cause disease in susceptible animals, it can alter the immune response of infected mice.   Adventitious infections of laboratory mice with both parvoviruses continue to occur.   This recurrence is attributed to the virus being both relatively stable in the environment and resistant to many disinfection procedures.   The virus also has a predilection for dividing cells, hence can be a contaminant rodent-derived biologics such as tumor cell lines.   Exclusion of this pathogen routinely involves indirect sentinel health surveillance system.   Some have shown, though, that efficient transmission of pathogen to sentinels may not occur when prevalence of infection is low.   There has been conflicting information regarding sentinel age and resistance to infection.  A recent study found that sentinel age did not affect MPV1 infection, which is the opposite of what earlier studies have shown.

 

The authors of this study, along with others, have noted that C57BL/6 (B6) mice are less likely to be MPV1 seropositive, even if MPV1 infection is widespread.   This study used a representative field strain, MPV1e, to determine whether the resistance of B6 mice compared to BALB/c (C) mice to infection with MPV1 varied with inoculation route.   They used oral gavage to simulate natural infection.   The second inoculation route used was intraperitoneal (IP).  They evaluated whether infection correlated with differences in the time course, and levels of viral infection, replication and shedding and of humoral immunity.  

 

Mice were inoculated with the virus either IP or by oral gavage.   Feces were collected antemortem from both strains at 1 and 2 d post-inoculum and postmortem on days 42 and 56.  Three mice from each strain were euthanized by CO2 inhalation at 3, 5, 7, 10, 14, 21, 28, 42, and 56 days after inoculation.   Blood, fecal pellets, mesenteric lymph nodes (MLN), spleen, and ileum were aseptically collected for analysis.

 

ID50 for both inoculation routes for C and B6 mice were determined.   Mice of each strain received serial dilutions either by gavage of IP injection to determine the effect of inoculation route on susceptibility to infection.   The ID50 for both inoculum routes were higher for C mice compared with B6 mice.   The results from the ID50 confirmed that C mice were more susceptible than B6 mice to MPV1e infection.  

 

ELISA and PCR results were in agreement for 78 of the 79 mice that were administered titrations of varying doses of MPV1e.   According to the authors, this agreement demonstrated that MPV1e infection consistently elicited a humoral immune response in both mouse strains, a finding supported by other studies.   These results contradicted the belief that B6 mice do not seroconvert when infected with a low dose of MPV1.

 

The authors used qPCR to determine the amount of MPV1e DNA in tissues and feces.   RT-qPCR measured MPV1e mRNA in tissues and evaluated the amount of viral replication.  In C mice, MPV1e infection, replication, and fecal shedding peaked between 3 and 10 days post inoculation.  In B6 mice, the authors found that the peaks of infection and viral shedding occurred 2 to 3 d later and were significantly lower than those found in C mice.  Results showed that changes in levels of viral replication and fecal shedding closely followed one another.   Viral replication was no longer detected in tissues 56d post inoculation.   Viral shedding in feces was undetectable in B6 mice and was reduced by 3 logs in C mice 56 d post inoculation.   qPCR results for tissue samples showed that infection levels peaked at 28d post infection then remained stable though study conclusion at 56d post infection.  Infection persisted in tissues of C mice at concentrations that were significantly higher than those in B6 mice.   Results of this study supported that B6 mice are less susceptible to MPV1e infection than C mice.   This susceptibility was independent of route of inoculation.

 

QUESTIONS

1. Mouse Parvovirus is:

a.  Double stranded RNA virus

b. Single stranded RNA virus

c.  Double stranded DNA virus

d.  Single stranded DNA virus

2.  The most common parvovirus of laboratory mice is:

a.  Mouse parvovirus

b.  Mouse minute virus

3.  One reason that parvoviruses are environmentally stable is because they are enveloped.  T or F

4.  Authors of this study concluded that B6 mice were less susceptible to MPV1e infection and do not consistently seroconvert once infected.   T or F

 

ANSWERS

1.  d     

2. a     

3. F     

4. F       

Alvarado et al. Pathogenicity of Helicobacter ganmani in Mice Susceptible and Resistant to Infection with H. hepaticus, pp. 15-22 

Primary Species: Mouse (Mus musculus)

 

SUMMARY: Helicobacter hepaticus is the most notorious of the murine helicobacters found in laboratory rodents. However, H. ganmani has been isolated from intestines of many laboratory mice, producing intestinal disease in immunodeficient mice. The study aimed to evaluate the effect of H. ganmani infection on intestinal disease and to characterize alterations of inflammatory gene expression associated with infection in immunocompetent and immunodeficient mice. A total of 60 female A/JCr mice, 60 female B6 mice and 60 female IL10 KO mice, all 4 wk of age, were used in this study. Within each strain, 20 mice were assigned to H. ganmani-inoculated, H. hepaticus-inoculated and control groups; and cecal tissue and contents were harvest at 4d and 90d post oral gavage inoculation for detection of infection and bacterial quantification by qPCR. Intestinal disease was also evaluated by using a scoring system (0, no inflammation; 1, mild; 2, moderate; and 3, severe). In addition, ceca were assessed for hyperplasia. Cecal gene expression of IFNγ and IL 12/23 was analyzed since are proinflammatory signaling molecules for the manifestation of typhlitis. Mice inoculated with H. ganmani showed similar or significantly more copies of cecum-associated Helicobacter DNA than did mice inoculated with H. hepaticus. Cecal lesion scores at 4 and 90 d post inoculation were not significantly greater in all strains for H. ganmini-inoculated group in comparison with the control group. Gene expression results showed that H. ganmani infection did not cause significant elevation of IFNγ in any of the mice strains. However, in IL10 KO mice, H. ganmani infection was associated with a significant increase in the expression of cytokine IL12/23. Finally, H. ganmani infection did not induce typhlitis as H. hepaticus infection did but H. ganmani was associated with alteration in inflammatory cytokines in IL10-deficient mice.

 

QUESTIONS

1.  T or F. The hallmarks of infection by H. hepaticus in mice are typhlitis, colitis, and hepatitis

2.  H. hepaticus is not considered as a microbial trigger in susceptible mice strains for inflammatory bowel disease

3.  Co-infection of H. ganmani with other Helicobacter in mice has showed severe intestinal disease in mice

 

ANSWERS

1. T

2. T

3. F. No studies have been reported of the severity of intestinal disease in rodents due to the co-infection of H. ganmani with other Helicobacter

Rat Models

Geletneky et al. Pathology, Organ Distribution, and Immune Response after Single and Repeated Intravenous Injection of Rats with Clinical-Grade Parvovirus H1, pp. 23-35

Domain 1

Primary Species: Rat (Rattus norvegicus)

 

SUMMARY: Parvovirus H1 (H1PV) is an autonomous parvovirus that is transmitted in rodent populations. H1PV infection of human cancer cells caused strong oncolytic effects in preclinical models. For a clinical trial of H1PV in patients with brain tumors, clinical-grade H1PV was produced according to Good Manufacturing Practices. The main purpose of the 2 studies was to assess the potential toxicity profile of H1PV in rats as the natural host and thereby representing a model system that is permissive for virus replication, possibly enhancing deleterious effects. This report focuses on results obtained after a single high-dose intravenous injection of highly purified H1PV in 30 rats and multiple (n = 17) intravenous injections at 3 dose levels in 223 rats. In addition to providing safety information, the data offer insights into the biology of H1PV in the natural host including organ distribution, relative organ concentration, crossing of the blood-brain barrier, virus shedding, and immunologic reactions.

 

In studies, no virus-related mortality or macroscopic organ changes related to H1PV occurred. Histopathology after multiple virus injections revealed minimal diffuse bile duct hyperplasia in livers of animals of the highest dose group and germinal center development in spleens of animals from the high-dose group. Liver changes were reversible within a 2-wk recovery period after the last injection. In conclusion, all test results indicate that repeated injections of high doses of H1PV lead to only minor structural changes in the liver and that these changes are transient and are not accompanied by cellular damage.

 

Hematology, blood chemistry, and coagulation analyses did not reveal significant toxicologic changes due to H1PV. Virus injection stimulated the production of IgG antibodies but did not alter mononuclear cell function or induce cytokine release. PCR analysis showed dose-dependent levels of viral genomes in all organs tested. The virus was excreted primarily through feces (also present in urine and saliva but the amount of viral DNA were lower than in the feces). These data provide important information regarding H1PV infection in its natural host. The results of this study were mandatory for the regulatory approval of a clinical trial (ParvOryx01), which started in October 2011. Due to the confirmation of the favorable safety profile of H1PV in a permissive animal model, a phase I/IIa clinical trial of H1PV in brain tumor patients could be initiated.

 

QUESTIONS

1. T or F: The encouraging rates of complete remissions after intratumoral or intravenous H1PV injection of rats bearing large intracranial gliomas led to a clinical trial in patients with recurrent glioblastoma multiforme.

2. T or F: H1PV infection is nonpathogenic in rat and hamster of all ages

3. T or F: The persistence of viral DNA after 2 wk of recovery corroborates previously published results on rat parvoviruses, which showed that infectious parvovirus can be recovered from inoculated rats as late as 6 mo after infection.

4. Histopathology after multiple virus injections revealed minimal diffuse bile duct hyperplasia in livers of animals of the highest dose group. What does that mean in terms of the main route of clearance of H1PV?

 

ANSWERS

1. True

2. False. H1PV infection is nonpathogenic except in rat and hamster fetuses and newborns

3. True

4. The dose-dependent changes in the liver support that the main route of clearance of H1PV is via the reticuloendothelial system and digestive tract.

 

 

Geletneky et al. Bioavailability, Biodistribution, and CNS Toxicity of Clinical-Grade Parvovirus H1 after Intravenous and Intracerebral Injection in Rats, pp. 36-45

Domain 3: Research

Primary Species: Rat (Rattus norvegicus)

 

SUMMARY: Parvovirus H1 (H1PV) naturally occurs in the rat and is readily transmitted in rodent populations via fecal and oronasal routes.  The virus is unique in that the pathogenicity is dependent on the age at infection.  H1PV is pathogenic in newborns and is embryo- and fetotoxic.  The virus also has oncosuppressive and direct oncolytic properties which is the focus of this study.  The authors were looking at the tissue availability and biodistribution of H1PV after a single intravenous and intracranial injection and the potential CNS toxicity of H1PV after direct injection into the rat brain.  The H1 virus preparation conformed to the standards of GMP to ensure the purity, infectivity, and stability of the stock.  H1PV DNA was detected in almost all organs at all three time points (6h, 48hr, and 14 days pi) after intravenous and intracerebral injection.  The concentrations of H1PV were similar after intracranial and intravenous injections indicating that the virus has a high permeability of the blood-brain barrier.  The authors concluded that H1PV has significant advantages for possible therapeutic use including favorable tissue distribution and minimal CNS toxicity.   

 

QUESTIONS

1.  What species is the natural host of parvovirus H1 (H1PV)?

2.  a. What life stages are most significantly impacted by H1PV infection? 

  b. What life stage is minimally impacted by H1PV infection?

3.  What tissues had the highest concentration of H1PV?

4. In what tumor entity did H1PV show strong oncolytic effects?

 

ANSWERS

1. Rat

2. a. Infection in the middle of the gestation period results in fetal death.  Infection during late gestation or newborn results in osteolytic syndrome. 

     b. Infection of adults during ovular preimplantation does not result in fetal pathology.

3. Liver and spleen

4. Glioblastoma

 

Robinson et al. Four-Point Bending as a Method for Quantitatively Evaluating Spinal Arthrodesis in a Rat Model, pp. 46-50

Domain 3: Research

Primary Species: Rat (Rattus norvegicus)

 

SUMMARY: Rat spinal fusion models are commonly used to develop surgical techniques and grafting materials for use in human spinal fusion surgery for the treatment of lower back pain. The most common method for evaluating the efficacy of the procedures in the rat model is manual palpation, a qualitative assessment. This study sought to evaluate the use of four-point bending in a model of single posterolateral intertransverse process fusion, providing a quantitative data set. Explanted L4-L5 lumbar segments were isolated from twenty Sprague-Dawley rats (non-operated=3; operated=17), manually palpated and graded (fused [n=6], restricted motion [n=6], not fused [n=5]), then potted and mechanically tested with a four-point bending technique. Fused segments (n=6) were significantly different in stiffness compared to all other groups. No significant differences between “restricted motion” and “not fused” segments were detected but “restricted motion” segments were significantly stiffer than non-operated segments. Though the four-point bending technique has some limitations, this method validates the outcomes of qualitative manual palpation assessment and provides a quantitative data set to evaluate the success of spinal fusion surgery in a rat model.

 

QUESTIONS

1.   ApcPirc/+ and KAD rats are models of what human disease?

a.  Crigler-Najjar Syndrome (hereditary unconjugated bilirubinemia)

b.  Insulin-dependent diabetes mellitus

c.  Familial colon cancer

d. Multiple sclerosis

2.  Which rat strain serves as a host for transplantable Morris hepatomas?

a.  Brown Norway

b.  Lewis

c. Buffalo

d. Fischer 344

3.  True or False. Despite having a rudimentary thymus (athymic), tonsillar tissue can be isolated from nude rats.

 

ANSWERS

1.   c

2.   c

3.  False – Rats (and mice) do not have tonsils

Avian Model

Siddalls et al. Infestation of Research Zebra Finch Colony with 2 Novel Mite Species, pp. 51-53

Domain 1; Task 2; K 1 and 2

Tertiary Species: Other birds

SUMMARY: Zebra Finches (Taeniopygia guttata) are commonly used in neurobiology and behavior studies. They are often sourced from other investigators or non-commercial sources that have a poorly defined health status. This case report describes 2 novel mite species. Initially birds were observed with “moving dandruff” on them. Microscopic examination quickly revealed the presence of 2 different types of mites. Heavy infestations were linked to poor health with clinical signs including closed eyes and ruffled feathers. An entomologist confirmed that the 2 species of mites were previously undescribed. The less frequently identified mite was a novel ‘true’ feather mite in the genus Megninialges. The second more prolific mite, Neicheyletiella parvisetosa, while not a true feather mite was living in the feathers where they construct silken nests. Using a pyrethrin-based spray, 6 treatments at 2 week intervals was required to eradicate the mites. Initially birds were sprayed in-situ, however the relative ineffectiveness of this lead to individual animal treatments. The stress of the treatments and the labor required for treatment lead to a shift in treatments to topical ivermectin (200 ug/kg in propylene glycol applied to the skin under the wing). This treatment was less labor intensive and effectively removed mites in 2 treatments. It was suspected that the mites were introduced in small numbers at a previous time and numbers amplified over time possible perturbed by environmental factors. Housing conditions, researcher manipulations and surgical procedures could further aggravate mite numbers through immunosuppression. Given the insidious nature of this infection the authors recommend that resident colonies be tested regularly for ectoparasites. 

QUESTIONS

1. Academic institutions routinely treat quarantined zebra finches against ectoparasites.

2. Name the two novel genus identified in this case report

3. What was the authors recommended treatment for ectoparasites on zebra finch?

ANSWERS

1. T

2. Megninialges sp. and Neicheyletiella parvisetosa

3. topical ivermectin (200 ug/kg in propylene glycol applied to the skin under the wing)

Swine Model

Beam et al. Comparison of Isoflurane and α-Chloralose in an Anesthetized Swine Model of Acute Pulmonary Embolism Producing Right Ventricular Dysfunction, pp. 54-61

Domain 2: Management of Pain and Distress

Primary Species: Pig (Sus scrofa)

 

SUMMARY: Pulmonary embolism (PE) is a leading cause of non-cardiac sudden death and is the third most common cause of cardiovascular morbidity. Individuals surviving a severe PE experience right heart damage with subsequent hypotension and circulatory shock. A model of this disease is needed for evaluating potential treatments targeted at reducing right heart failure.

 

In working to create this model, the authors evaluated two anesthetic regimens in swine to assess their hemodynamic effects. The swine that received α-Chloralose had lower HR, cardiac output, and higher SpO2, end tidal CO2, and MAP than did those receiving isoflurane. Intraexperiment mortality was 0 of 6 for α-Chloralose whereas it was 2 of 9 for isoflurane. The swine receiving α-Chloralose were shown to more closely mimic the hemodynamic consequences of PE in humans (sustained pulmonary hypertension, RV dilation, lowered end-tidal CO2, and had none of the confounding vasodilatory or coagulatory {widely variable fibrinogen and activated partial thromboplastin time} effects of isoflurane).  Accordingly, α-Chloralose proved to be a much better anesthetic choice as compared to isoflurane as it relates to this model.

 

The PE model was created by occluding the lobar and pulmonary arteries while the animal was under a surgical plane of anesthesia. Specifically, the occlusion occurred after injecting blood clots of various sizes by way of a jugular vein catheter at which time echocardiography was utilized to confirm the transmission of the clots through the right ventricle and into the lung.  Various hemodynamic and physiologic parameters were assessed in an intricate fashion (defined in detail in article) to verify the establishment of the model.   

 

QUESTIONS

1. Apart from its use in an acute terminal experiment as in this study, the authors advocate the use of α-Chloralose for chronic survival surgeries. (T or F)

2. The primary negative factor associated with isoflurane in this study is that of its vasodilatory properties which likely account for the subsequent elevated HR and low systolic arterial BP. (T or F) 

 

ANSWERS

1. False (due to problems associated with the development of adynamic ileus)

2. True    

 

 

Nonhuman Primate Models

Ng et al. Use of Genome-wide Heterospecific Single-Nucleotide Polymorphisms to Estimate Linkage Disequilibrium in Rhesus and Cynomolgus Macaques, pp. 62-69

Domain 3 – Research; Task: T3 – design and conduct research; Knowledge:  6 – characterization of animal models (phenotyping, behavioral assessment)

Primary Species: Macaques (Macaca spp.)

SUMMARY: Study compared the linkage disequilbrium (LD) between macaque species (Chinese, Indian and cynomolgus).  Using 1781 SNPs and 183 (97 Chinese and 86 Indian rhesus) rhesus blood samples and blood samples from 96 cynomolgus macaques, results confirm that all three species are very genetically diverse. Their results unexpectedly revealed that the Chinese macaques had lower genetic diversity, but they attributed the finding to the ascertainment bias the SNPs were chosen by. This study did confirm that cynomolgus exhibited a lower rate of decay compared to both rhesus macaques making them an ideal species in genome-wide associated studies. 

QUESTIONS

1.  What is linkage disequilibrium (LD)?

2.  What influences LD?

3.  What two characteristics does this study use to quantify genetic diversity?

ANSWERS

1.  Linkage disequilbrium is the non-random association of alleles at two or more loci that descend from a single chromosome.  LD is a measurement of proximal genomic space that occurs in a population. 

2.  LD is influenced by rate of recombination, mutation, genetic drift, non-mating and population structure. 

3.  Genetic diversity is defined as heterozygosity and minor allele frequency. 

Yasmin et al. Detection and Quantification of Male-Specific Fetal DNA in the Serum of Pregnant Cynomolgus Monkeys (Macaca fascicularis), pp. 70-76

Domain 3: Research; Task T3 - Design and conduct research; Knowledge Topic K2 - Research Methods

Primary Species: Macaques (Macaca spp.)

 

SUMMARY: The detection and analysis of cell free fetal nucleic acids in maternal plasma or serum has allowed for early detection of several conditions in a developing fetus, including sex determination and inherited diseases. This is a technically challenging technique, as fetal DNA concentrations in maternal serum are low (only 3 to 6% of total free DNA in plasma) and cannot easily be differentiated from maternal DNA. However, the detection of a male fetus is relatively simple and highly accurate in humans as early as 7 weeks of gestation. Due to the usefulness of non-human primate models in studying human diseases, it is important to also study cell free fetal DNA in non-human primate models to aid the progress of fetal developmental research that is applicable to human health. In this study, the authors developed a standardized PCR system to detect male specific fetal DNA in maternal serum of cynomolgus macaques at different time points during gestation, using male specific sex associated markers used widely in humans,  sex-determining-region Y ( SRY), testis-specific-protein Y linked (TSPY) and DYS14. These markers were selected because the SRY gene is single copy and thus highly specific, while the DYS14 and TSPY genes are multicopy and yield increased sensitivity for the assay.

They hypothesized that they could predict fetal sex of cynomolgus monkeys at different stages of gestation. Blood samples were taken from pregnant monkeys at 5, 12, or 22 weeks gestation, and blood was centrifuged at 1700 x g for 15 minutes to pellet cells and allow removal of serum. As positive and negative controls blood was also taken from male and female monkeys for extraction of genomic DNA. DNA was extracted using a commercially available kit and an automated extraction system. Male specific targets were amplified using TaqMan PCR assay and primer sequences for the target genes based on Rhesus monkeys. To determine the detection limits of the assay and quantify the number of targets within each sample, a standard curve was generated by cloning amplicons of each gene amplified from male specific genomic DNA into appropriate plasmid vectors. Plasmids were them serially diluted for use as a standard curve in the quantitative PCR assay. The primers for the selected targets were demonstrated to have good specificity as appropriately sized targets were successfully amplified from genomic DNA from males, but not females. Sequence analysis revealed 85% sequence homology with the human TSPY gene and 100% homology with two other macaque species, M. mulatta and M. fuscata. Male specific SRY and DYS14 targets were amplified from maternal serum in 28 monkeys, thus the authors predicted those dams were gestating male fetuses. In 18 dams, no amplification of male specific targets was seen, thus the authors predicted those dams were gestating female fetuses. At delivery, it was determined that the real time PCR assay was in 100% accordance with fetal sex determination and all male bearing pregnancies had detectable levels of male DNA in the maternal serum. The lowest amount of DNA detectable was determined to be 1.0x101 DNA copies per 40uL of serum. Male DNA was detectable in maternal serum at all time points tested. From this study, the authors concluded that they could predict fetal sex with high accuracy by amplifying male specific DNA from maternal serum. The selected primers and probes proved to be successful for detecting male specific DNA in a laboratory setting. The real time PCR analysis used in this study was a highly sensitive, specific, and non-invasive method for detecting male specific DNA from maternal serum.

 

QUESTIONS

1. T/F. Detection of multicopy genes, such as DYS14, increases specificity of the assay.

2. What other macaque species have high sequence homology of the DYS14 and SRY genes with M. fascicularis?

a. M. mulatta

b. M. fuscata

c. M. nemestrina

d. All of the above

e. a and b only

3. T/F. Detection of DYS14 and SRY DNA in maternal serum as early as 5 weeks gestation accurately predicted sex of the fetus with 100% accordance at time of delivery.

 

ANSWERS

1. False. Detection of multicopy genes increases sensitivity of the assay.

2. e

3. True

 

 

Lester McCully et al. Development of a Cerebrospinal Fluid Lateral Reservoir Model in Rhesus Monkeys (Macaca mulatta), pp. 77-82

Domain 1 and 3

Primary Species: Macaques (Macaca spp.)

 

SUMMARY: Serial ventricular collection of CSF and/or intraventricular drug administration in NHPs is common in many studies.

It is typically accomplished by two established models of which both are closed, indwelling, subcutaneous systems that allow collection/administration in restrained, anaesthetized NHPs

1.   4th ventricle model (FR) or previously known as the Ommaya reservoir (see figure below; A)

• Catheter is placed in 4th ventricle through the aqueduct of Magendie

• Connected to a silastic reservoir implanted SC over the occipital bone

• Able to “pump” reservoir to circulate CSF to maintain unbiased samples (bidirectional flow)

• Typically has a low rate of successful establishment

o Hypothesis that catheter blocks CSF flow and causes hydrocephalus

o Bleeding of the choroid plexus may also lead to patency problems

• Established FR models remain patent for long periods w/o neurologic sequelae

• Post-surgical care is extensive requiring prolonged periods of analgesics and steroids

2.  Lateral port (LP) model (see figure below; B)

• Catheter implanted in the lateral ventricles and connected to a SC, IV access port

• Percutaneous sampling and drug administration

• This model is a static model as CSF is not circulated and flow is unidirectional

• CSF sampling is restrictive as the volume (dead space) must be removed to get unbiased sample

• Collection by gravitational flow (not aspiration) and frequency dependent on rate of replacement

• Choroid plexus blood contamination possible, but hydrocephalus is avoided with this model

• Less recovery time, less analgesic and steroid use, and a high rate of successful establishment vs. FR model

Authors sought to combine models to get the functionality of the FR model with the success of establishment and quicker recovery of the LP model.

1.   Description of the Lateral ventricular reservoir model (LR)

• Closed, indwelling, and subcutaneous system with circulating CSF flow and unrestrictive sampling

• Hypothesis that new method would avoid post-surgical hydrocephalus, nonpatency issues, prolonged recovery and care

• Catheter placement in the lateral ventricle using MRI coordinates and a stereotactic device. The reservoir is attached to the ventricular catheter and implanted SC on the parietal bone (see figure below; C)

2.  Results of LR model

• LR systems remained functional at 221 days in 67% of animals studied (6/9), 56% retained function for 352 days, and 44% had continued functionality at 426-510 days

• The three failed cases had unavoidable choroid plexus resulting in bleeding and non-patency

• In comparison to the FR model (internal data comparison): 72% improvement of successful establishment rate (SER) at 4 months, 33% improvement SER at 1 year, 90% reduction in days of abnormal food intake, 46% reduction in duration of analgesic use, 38% reduction in duration of steroid use, 62% decrease in abnormal CSF collection, and 53% reduction in duration of post-op recovery.

3.   Conclusions

• The combination of circulating CSF flow and unrestricted sampling combined with better post-op recovery makes this model of CSF collection and drug administration an advantageous alternative to the 2 other commonly used models.

[pic]

QUESTIONS

1. Which of the following models for collection of CSF allows for circulation of the CSF and prevents sampling bias?

a.  The 4th ventricle model

b. The lateral port model

c.  The lateral ventricular reservoir model

d.  a and b

e.  b and c

f.  a and c

2. T/F. The lateral port model was developed for intrathecal drug administration.

3. T/F. The sole purpose or function of the choroid plexus is to produce CSF.

 

ANSWERS

1.   f

2.  T

3. F

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