A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
Abstract Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-11-01
|
| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-021-00281-0 |
| _version_ | 1798034855422853120 |
|---|---|
| author | James P. McAllister Michael R. Talcott Albert M. Isaacs Sarah H. Zwick Maria Garcia-Bonilla Leandro Castaneyra-Ruiz Alexis L. Hartman Ryan N. Dilger Stephen A. Fleming Rebecca K. Golden Diego M. Morales Carolyn A. Harris David D. Limbrick |
| author_facet | James P. McAllister Michael R. Talcott Albert M. Isaacs Sarah H. Zwick Maria Garcia-Bonilla Leandro Castaneyra-Ruiz Alexis L. Hartman Ryan N. Dilger Stephen A. Fleming Rebecca K. Golden Diego M. Morales Carolyn A. Harris David D. Limbrick |
| author_sort | James P. McAllister |
| collection | DOAJ |
| description | Abstract Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. Methods Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed. Results Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45–55 days, (p < 0.001). Past the post-induction recovery period, untreated pigs were asymptomatic despite exhibiting mild-moderate ventriculomegaly. Three out of 4 shunted animals showed a reduction in ventricular volume after 20–30 days of treatment, however some developed ataxia and lethargy, from putative shunt malfunction. Conclusions Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus. |
| first_indexed | 2024-04-11T20:50:12Z |
| format | Article |
| id | doaj.art-73f88d36430b4518b7d5660ba1adf8ef |
| institution | Directory Open Access Journal |
| issn | 2045-8118 |
| language | English |
| last_indexed | 2024-04-11T20:50:12Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj.art-73f88d36430b4518b7d5660ba1adf8ef2022-12-22T04:03:52ZengBMCFluids and Barriers of the CNS2045-81182021-11-0118111710.1186/s12987-021-00281-0A novel model of acquired hydrocephalus for evaluation of neurosurgical treatmentsJames P. McAllister0Michael R. Talcott1Albert M. Isaacs2Sarah H. Zwick3Maria Garcia-Bonilla4Leandro Castaneyra-Ruiz5Alexis L. Hartman6Ryan N. Dilger7Stephen A. Fleming8Rebecca K. Golden9Diego M. Morales10Carolyn A. Harris11David D. Limbrick12Department of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Surgery, Division of Neurosurgery, University of Calgary School of MedicineDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Animal Sciences, Division of Nutritional Sciences, Neuroscience Program, University of Illinois, Champagne-UrbanaDepartment of Animal Sciences, Division of Nutritional Sciences, Neuroscience Program, University of Illinois, Champagne-UrbanaDepartment of Animal Sciences, Division of Nutritional Sciences, Neuroscience Program, University of Illinois, Champagne-UrbanaDepartment of Neurosurgery, Washington University in St. Louis School of MedicineDepartment of Chemical Engineering and Materials Science, Wayne State UniversityDepartment of Neurosurgery, Washington University in St. Louis School of MedicineAbstract Background Many animal models have been used to study the pathophysiology of hydrocephalus; most of these have been rodent models whose lissencephalic cerebral cortex may not respond to ventriculomegaly in the same way as gyrencephalic species and whose size is not amenable to evaluation of clinically relevant neurosurgical treatments. Fewer models of hydrocephalus in gyrencephalic species have been used; thus, we have expanded upon a porcine model of hydrocephalus in juvenile pigs and used it to explore surgical treatment methods. Methods Acquired hydrocephalus was induced in 33–41-day old pigs by percutaneous intracisternal injections of kaolin (n = 17). Controls consisted of sham saline-injected (n = 6) and intact (n = 4) animals. Magnetic resonance imaging (MRI) was employed to evaluate ventriculomegaly at 11–42 days post-kaolin and to plan the surgical implantation of ventriculoperitoneal shunts at 14–38-days post-kaolin. Behavioral and neurological status were assessed. Results Bilateral ventriculomegaly occurred post-induction in all regions of the cerebral ventricles, with prominent CSF flow voids in the third ventricle, foramina of Monro, and cerebral aqueduct. Kaolin deposits formed a solid cast in the basal cisterns but the cisterna magna was patent. In 17 untreated hydrocephalic animals. Mean total ventricular volume was 8898 ± 5917 SD mm3 at 11–43 days of age, which was significantly larger than the baseline values of 2251 ± 194 SD mm3 for 6 sham controls aged 45–55 days, (p < 0.001). Past the post-induction recovery period, untreated pigs were asymptomatic despite exhibiting mild-moderate ventriculomegaly. Three out of 4 shunted animals showed a reduction in ventricular volume after 20–30 days of treatment, however some developed ataxia and lethargy, from putative shunt malfunction. Conclusions Kaolin induction of acquired hydrocephalus in juvenile pigs produced an in vivo model that is highly translational, allowing systematic studies of the pathophysiology and clinical treatment of hydrocephalus.https://doi.org/10.1186/s12987-021-00281-0HydrocephalusAnimal modelsKaolinAcquired hydrocephalusShuntVentriculomegaly |
| spellingShingle | James P. McAllister Michael R. Talcott Albert M. Isaacs Sarah H. Zwick Maria Garcia-Bonilla Leandro Castaneyra-Ruiz Alexis L. Hartman Ryan N. Dilger Stephen A. Fleming Rebecca K. Golden Diego M. Morales Carolyn A. Harris David D. Limbrick A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments Fluids and Barriers of the CNS Hydrocephalus Animal models Kaolin Acquired hydrocephalus Shunt Ventriculomegaly |
| title | A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| title_full | A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| title_fullStr | A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| title_full_unstemmed | A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| title_short | A novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| title_sort | novel model of acquired hydrocephalus for evaluation of neurosurgical treatments |
| topic | Hydrocephalus Animal models Kaolin Acquired hydrocephalus Shunt Ventriculomegaly |
| url | https://doi.org/10.1186/s12987-021-00281-0 |
| work_keys_str_mv | AT jamespmcallister anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT michaelrtalcott anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT albertmisaacs anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT sarahhzwick anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT mariagarciabonilla anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT leandrocastaneyraruiz anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT alexislhartman anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT ryanndilger anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT stephenafleming anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT rebeccakgolden anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT diegommorales anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT carolynaharris anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT daviddlimbrick anovelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT jamespmcallister novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT michaelrtalcott novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT albertmisaacs novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT sarahhzwick novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT mariagarciabonilla novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT leandrocastaneyraruiz novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT alexislhartman novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT ryanndilger novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT stephenafleming novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT rebeccakgolden novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT diegommorales novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT carolynaharris novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments AT daviddlimbrick novelmodelofacquiredhydrocephalusforevaluationofneurosurgicaltreatments |