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Uttio Roy Chowdhury, Bradley Holman, Cheryl Hann, Cindy Bahler, Michael Fautsch; A Novel Rat Model to Study the Role of Intracranial Hypotension in Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2292.
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Retrospective studies from our laboratory have identified low cerebrospinal fluid pressure (CSFP) as a risk factor for glaucoma. The low CSFP will presumably be reflected in a proportionally lowered intracranial pressure (ICP). Unfortunately, there are no existing animal models to investigate the role of ICP and the glaucoma phenotype. In the current study, we developed a rat model that can be used to manipulate ICP, and eventually be used to study the role of ICP on optic neuropathy.
Brown Norway rats (n=3, retired breeders, age >8 months, weight > 300 g) were surgically implanted with a 20 gauge cannula into the lateral ventricle. The cannula was held in place by dental cement and secured to the skull with 4 screws. An external 3 mm post was connected to PE60 tubing protected by a flexible metal tether. The tether was connected to a swivel mount that enabled movement within the cage. The tubing was attached to a pressure transducer connected to a computer that recorded ICP in real-time. An artificial CSF syringe column was attached in series and positioned at head-level. Lowering of the column enabled manual reduction of ICP. After completion of data collection, rats were sacrificed and processed for histological analysis. Daily ICP was calculated by averaging 24 hours of consecutive data.
Rats undergoing manual manipulation resulting in chronic depression of ICP showed no signs of apparent discomfort during length of experiments which lasted up to 3 months. Baseline ICP for rats was 4.1 ± 1.0 mmHg (n=3). Lowering of artificial CSF column by 2-cm below head level reduced ICP to 2.4 ± 1.3 mmHg (n=3), nearly 50% below baseline levels. Histological studies confirmed correct cannula placement and indicated minimal invasive damage to brain tissues.
We have developed a unique and viable rat model to study the effect of reduced intracranial ICP on optic neuropathies.
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