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  • Insights into the Pathogenesis of Papilledema in an Experimental Model of Hydrocephalus

    Final Number:

    Satish Krishnamurthy MD, MCh; J Li MD; Kenneth Jenrow PhD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2011 Annual Meeting

    Introduction: Pathogenesis of papilledema is unknown. Several conditions such as raised intracranial pressure, venous sinus thrombosis, hydrocephalus and others are known to be associated with papilledema. Although elevated venous pressure and venous occlusion are regarded as primary factors responsible for papilledema, experimental models that replicate these conditions do not result in papilledema (2). We present our findings in an animal model of hydrocephalus (1).

    Methods: Hyperosmotic 10KD fluorescent labeled dextran solution was infused into the lateral ventricle (in 40 animals) through osmotic pump chronically in normal adult Sprague-Dawley rats. Hydrocephalus was demonstrated by MRI scan in the chronically infused animals (see figure) and animals were sacrificed at the end of the experiments. The brain tissue, the optic nerves, the 5th cranial nerve and spinal cord were cut for histology examination and immunohistochemistry stains for the particles distribution. Our results related to optic nerve findings will be presented here.

    Results: Fluorescent dextran particles were found in the substance of the optic nerve uniformly in animals with hydrocephalus (see figure with optic nerve section). Microscopic examination of the location of these particles show close proximity of the labeled dextran to the capillaries and some of the particles were clearly intracellular in microglia. Since the dextran solution was infused intraventricularly, we believe that the dextrans gained access to the optic pathways through the third ventricle.

    Conclusions: Transport of intraventricularly administered dextran particles into the optic nerves has not been previously reported. Their occurrence in this animal model of hydrocephalus suggests that transport through the optic nerves is a mechanism of egress of excess macromolecules similar to egress through the olfactory pathways. Since infusion of macromolecules such as thrombin into the brain causes brain edema, we hypothesize that excess macromolecules draw water into the optic nerve and result in papilledema.

    Patient Care: Understanding the pathogenesis of papilledema will help us design treatment strategies and early recognition to prevent visual loss from papilledema.

    Learning Objectives: By the conclusion of the session, participants should be able to:1) Describe the current understanding of papilledema, 2) Describe the experimental model of hydrocephalus, 3) Describe the hypothesis proposed in light of transportation of macromolecules through the optic nerve.

    References: 1.Krishnamurthy S, Li J, Schultz L, McAllister JPII: Intraventricular infusion of hyperosmolar dextran induces hydrocephalus: a novel animal model of hydrocephalus. Cerebrospinal Fluid Research December 2009 6(1):16. 2. Schirmer CM, Hedges TR 3rd. Mechanisms of visual loss in papilledema. Neurosurg Focus 2007: 23(5):E5. 3. Lee KR, Betz AL, Keep RF, Chenevert TL, Kim S, Hoff JT: Intracerebral infusion of thrombin as a cause of brain edema. J Neurosurg 1995 Vol 83(6): 1045-1051

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