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...

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Autores principales: 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
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Publicado: BMC 2021
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spelling oai:doaj.org-article:73f88d36430b4518b7d5660ba1adf8ef2021-11-14T12:07:05ZA novel model of acquired hydrocephalus for evaluation of neurosurgical treatments10.1186/s12987-021-00281-02045-8118https://doaj.org/article/73f88d36430b4518b7d5660ba1adf8ef2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12987-021-00281-0https://doaj.org/toc/2045-8118Abstract 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.James P. McAllisterMichael R. TalcottAlbert M. IsaacsSarah H. ZwickMaria Garcia-BonillaLeandro Castaneyra-RuizAlexis L. HartmanRyan N. DilgerStephen A. FlemingRebecca K. GoldenDiego M. MoralesCarolyn A. HarrisDavid D. LimbrickBMCarticleHydrocephalusAnimal modelsKaolinAcquired hydrocephalusShuntVentriculomegalyNeurology. Diseases of the nervous systemRC346-429ENFluids and Barriers of the CNS, Vol 18, Iss 1, Pp 1-17 (2021)
institution DOAJ
collection DOAJ
language EN
topic Hydrocephalus
Animal models
Kaolin
Acquired hydrocephalus
Shunt
Ventriculomegaly
Neurology. Diseases of the nervous system
RC346-429
spellingShingle Hydrocephalus
Animal models
Kaolin
Acquired hydrocephalus
Shunt
Ventriculomegaly
Neurology. Diseases of the nervous system
RC346-429
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
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.
format article
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
title 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_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_sort novel model of acquired hydrocephalus for evaluation of neurosurgical treatments
publisher BMC
publishDate 2021
url https://doaj.org/article/73f88d36430b4518b7d5660ba1adf8ef
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