title: Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus.
abstract: It has been assumed that the pathogenesis of hydrocephalus includes a cerebrospinal fluid (CSF) absorption deficit. Because a significant portion of CSF absorption occurs into extracranial lymphatics located in the olfactory turbinates, the purpose of this study was to determine whether CSF transport was compromised at this location in a kaolin-induced communicating (extraventricular) hydrocephalus model in rats. Under 1-3% halothane anesthesia, kaolin (n = 10) or saline (n = 9) was introduced into the basal cisterns of Sprague-Dawley rats, and the development of hydrocephalus was assessed 1 wk later using MRI. After injection of human serum albumin ((125)I-HSA) into a lateral ventricle, the tracer enrichment in the olfactory turbinates 30 min postinjection provided an estimate of CSF transport through the cribriform plate into nasal lymphatics. Lateral ventricular volumes in the kaolin group (0.073 +/- 0.014 ml) were significantly greater than those in the saline-injected animals (0.016 +/- 0.001 ml; P = 0.0014). The CSF tracer enrichment in the olfactory turbinates (expressed as percent injected/g tissue) in the kaolin rats averaged 0.99 +/- 0.39 and was significantly lower than that measured in the saline controls (5.86 +/- 0.32; P < 0.00001). The largest degree of ventriculomegaly was associated with the lowest levels of lymphatic CSF uptake with lateral ventricular expansion occurring only when almost all of the lymphatic CSF transport capacity had been compromised. We conclude that lymphatic CSF absorption is impaired in a kaolin-communicating hydrocephalus model and that the degree of this impediment may contribute to the severity of the induced disease.
authors.affiliation: Neuroscience Program, Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Nagra
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J P
authors.initials: JP
authors.lastname: McAllister
authors.forename: J
authors.initials: J
authors.lastname: Miller
authors.forename: M
authors.initials: M
authors.lastname: Wagshul
authors.forename: M
authors.initials: M
authors.lastname: Johnston
mesh_terms: D000818:Animals; D001099:Arachnoid / Q000033:anatomy & histology / Q000378:metabolism; D002552:Cerebral Ventricles / Q000033:anatomy & histology; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004396:Coloring Agents; D005070:Evans Blue; D005260:Female; D006849:Hydrocephalus / Q000134:cerebrospinal fluid* / Q000139:chemically induced / Q000473:pathology; D007616:Kaolin; D042601:Lymphatic Vessels / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009830:Olfactory Bulb / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014420:Turbinates / Q000033:anatomy & histology / Q000378:metabolism
chemical_list: D004396:Coloring Agents; D007616:Kaolin; D005070:Evans Blue