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Browsing by Author "Berbari, Nick"
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Item Effects of Hydrocephalus on Rodent Optic Nerve and Optic Disc(2021-08) McCue, Rachel A.; Belecky-Adams, Teri; Blazer-Yost, Bonnie; Mao, Weiming; Baucum, A.J.; Berbari, NickHydrocephalus affects 1 in 1,000 newborns and nearly 1,000,000 Americans, leading to an increase in intercranial pressure due to the build-up of cerebrospinal fluid. There are numerous complications that arise as a result of hydrocephalus, but this study focuses on optic disc edema. The subarachnoid space surrounding the optic nerve contains cerebrospinal fluid. The cerebrospinal fluid increases in hydrocephalus, putting pressure on the optic nerve. The additional intracranial pressure has been proposed to cause axoplasmic stasis within the retinal ganglion cell axons, leading to axonal damage and retinal ischemia. The purpose of this study was to determine the effects of hydrocephalus on the optic disc and retina in several animal models of hydrocephalus. This study uses two genetic and two injury-induced models of hydrocephalus in addition to immunohistochemistry and histological stains to examine the optic disc, thickness of retinal layers, and numbers of retinal cells. This study serves as preliminary work to help build the case that hydrocephalus causes cell loss in the retina, as well as swelling of the retinal ganglion cell axons, leading to axoplasmic stasis and cell death.Item TRPV4 in the Choroid Plexus Epithelium: Pathway Analysis and Implications for Cerebrospinal Fluid Production(2019-12) Preston, Daniel; Blazer-Yost, Bonnie; Belecky-Adams, Teri; Clack, James; Berbari, NickHydrocephalus is a disease characterized by an increase in cerebrospinal fluid (CSF) in the ventricles of the brain. This manifests as a result of either overproduction or underabsorption of CSF leading to increases in pressure, swelling and loss of brain matter. Current treatments for this disease include surgical interventions via the introduction of shunts or endoscopic third ventriculostomy, both of which aim to redirect flow of CSF in to another cavity for absorption. Limited pharmacotherapies are available in the treatment of hydrocephalus, and there exists a clinical need for drug therapies, which can ameliorate the pathophysiology associated with hydrocephalus and ventriculomegaly. CSF is produced primarily by the choroid plexus (CP), found in the ventricles of the brain. Composed of a high resistance epithelium surrounding a capillary network, the CP epithelium acts as a barrier, regulating ion transport between the CSF and blood. Transient Receptor Potential Vanilloid-4 (TRPV4) is a nonselective Ca2+-permeable cation channel expressed in the CP which is being investigated for its role in CSF production. To study hydrocephalus, we utilize two model systems; the TMEM67-/- Wpk rat, and the PCP-R cell line. The Wpk rat model is used to study the effects of drug intervention on the development and progression of hydrocephalus. The PCP-R cell line is utilized for studies which aim to understand the mechanisms by which CSF is produced. Using Ussing chamber electrophysiology, we are able to study the role of specific channels, transporters and modulators in driving epithelial ion flux across the CP. This research aims to establish a role for TRPV4 in production and regulation of CSF, and to interrogate a mechanism by which this ion transport occurs. The chapters that follow describe components of the pathway by which TRPV4 is activated and ion flux is stimulated.