title: Noninvasive early detection of brain edema in mice by near-infrared light scattering.
abstract: Brain edema accounts for significant morbidity and mortality in many neurologic conditions such as head trauma, stroke, meningitis, and brain tumor. The water channel aquaporin-4 (AQP4) has been found to be an important determinant of brain water accumulation and clearance of excess brain water. We report the development of a noninvasive near-infrared (NIR) light-scattering method to compare the early kinetics of brain swelling in normal and AQP4-deficient mice. Brain tissue was illuminated through the intact skull with NIR light at 850 nm, and steady-state scattered light intensity was monitored at an angle of 90 degrees at a position on the skull approximately 10 mm from the illuminated site. NIR light scattering reversibly increased with brain swelling (DeltaI/Io approximately 25% per 1% increase in brain water content), but was insensitive to changes in cerebral blood flow, blood oxygenation, or blood flow-related changes in intracranial pressure (ICP). DeltaI/Io increased approximately linearly with brain water content as measured by wet-to-dry weight ratios. Acute water intoxication (intraperitoneal water, 20% body weight) produced a gradual increase in DeltaI/Io of 12 +/- 4% in wild-type mice at 5 min, much greater than that of 2 +/- 1% in AQP4-null mice. Correlation of the NIR signal with ICP showed that increased DeltaI/Io preceded measurable increases in ICP, indicating the ability of the NIR method to detect early brain edema before ICP elevation. NIR light scattering provides a simple noninvasive method to monitor brain edema in mice, with potential clinical applications.
authors.affiliation: Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, 94143-0521, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Thiagarajah
authors.forename: Marios C
authors.initials: MC
authors.lastname: Papadopoulos
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
mesh_terms: D000818:Animals; D051401:Aquaporin 4; D020346:Aquaporins / Q000172:deficiency / Q000235:genetics; D001929:Brain Edema / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012542:Scattering, Radiation; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins