Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus

doi:10.1152/ajpregu.00748.2007

Impaired lymphatic cerebrospinal fluid absorption in a rat model of kaolin-induced communicating hydrocephalus

G. Nagra,¹ J. Li,³ J. P. McAllister, II,² J. Miller,⁵ M. Wagshul,⁴ and M. Johnston¹

¹Neuroscience Program, Department of Laboratory Medicine and Pathobiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; ²Department of Neurosurgery, Division of Pediatric Neurosurgery, University of Utah School of Medicine, Salt Lake City, Utah; ³Department of Neurological Surgery, Wayne State University School of Medicine, University Health Center, Detroit, Michigan; ⁴Department of Radiology, Stony Brook University, Health Science Center L4-120, Stony Brook, New York; and ⁵DNA Sequencing and Analysis Facility, Central Michigan University, Mount Pleasant, Michigan

Submitted 16 October 2007 ; accepted in final form 27 February 2008

It has been assumed that the pathogenesis of hydrocephalus includesa cerebrospinal fluid (CSF) absorption deficit. Because a significantportion of CSF absorption occurs into extracranial lymphaticslocated in the olfactory turbinates, the purpose of this studywas to determine whether CSF transport was compromised at thislocation 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 basalcisterns of Sprague-Dawley rats, and the development of hydrocephaluswas assessed 1 wk later using MRI. After injection of humanserum albumin (¹²⁵I-HSA) into a lateral ventricle, the tracerenrichment in the olfactory turbinates 30 min postinjectionprovided an estimate of CSF transport through the cribriformplate into nasal lymphatics. Lateral ventricular volumes inthe kaolin group (0.073 ± 0.014 ml) were significantlygreater than those in the saline-injected animals (0.016 ±0.001 ml; P = 0.0014). The CSF tracer enrichment in the olfactoryturbinates (expressed as percent injected/g tissue) in the kaolinrats averaged 0.99 ± 0.39 and was significantly lowerthan that measured in the saline controls (5.86 ± 0.32;P < 0.00001). The largest degree of ventriculomegaly wasassociated with the lowest levels of lymphatic CSF uptake withlateral ventricular expansion occurring only when almost allof the lymphatic CSF transport capacity had been compromised.We conclude that lymphatic CSF absorption is impaired in a kaolin-communicatinghydrocephalus model and that the degree of this impediment maycontribute to the severity of the induced disease.

extraventricular hydrocephalus; ventriculomegaly; cribriform plate; olfactory turbinates; arachnoid villi and granulations; lymph; intracranial pressure

Address for reprint requests and other correspondence: M. G. Johnston, Neuroscience Research, Sunnybrook Health Sciences Centre, Univ. of Toronto, Research Bldg., S-111, 2075 Bayview Ave., Toronto, Ontario, M4N 3M5 (e-mail: miles.johnston{at}sunnybrook.ca) or J. P. (Pat) McAllister, Division of Pediatric Neurosurgery, University of Utah School of Medicine, 175 N. Medical Drive East, Salt Lake City, UT 84132-2303 (e-mail: pat.mcallister{at}hsc.utah.edu)