PROTEINURIA PRECEDES CEREBRAL EDEMA IN STROKE-PRONE RATS - A MAGNETIC-RESONANCE-IMAGING STUDY

Background and Purpose-Stroke-prone spontaneously hypertensive rats (S HRSP) subjected to high sodium intake develop severe hypertension, cer ebral edema, and proteinuria, culminating in organ damage and early de ath. MRI, which can be applied serially, provides the unique opportuni ty to study temporal and quantitative relations between these changes and whether-diminution of sodium intake can attenuate established cere bral edema. Methods-SHRSP were subjected to 1% NaCl in drinking water. Cerebral MRI, proteinuria and systolic blood pressure (SBP) were meas ured serially, After detection of cerebral edema (T2-weighted MRI), 6 rats were killed for histology, to confirm the diagnosis of cerebral e dema. The others were followed up for 7 more days while salt loading w as continued (n=10, group 1) or after sodium intake was normalized (n= 7, group 2). Results-SHRSP invariably developed cerebral edema in 30 d ays (range, 8 to 54 days). At this point neurological signs were absen t in 16 of 23 rats. SBP rose until 1 week before detection of cerebral edema, and then stabilized at approximately 265 mm Hg. Proteinuria in variably preceded cerebral edema, with a concentration exceeding 40 mg /d predicting development of cerebral edema in 9 days (range, 3 to 15 days). There was linear correlation (R=.62, P<.0001) between proteinur ia and cerebral edema (pixels with an intensity above a defined thresh old). Rats in group 1 showed an increase in cerebral edema (from 5.8+/ -1.1% to 13.5+/-2.8%; P<.05), and proteinuria remained high (from 305/-44 to 338+/-29 mg/d); and 2 died spontaneously. Rats in group 2 show ed no significant change in edema (from 4.9+/-0.5% to 6.9+/-1.3%) but a marked fall in proteinuria (from 294+/-34 to 119+/-10 mg/d; P<.05), both significantly different from group 1 (P<.05); all survived. SBP r emained unaltered in both groups. Conclusions-Our data establish MRI a s a sensitive method for detection of cerebral edema, often prior to n eurological signs, in SHRSP. Proteinuria predicts cerebral edema, and these two variables, both obtained noninvasively, are quantitatively r elated. Moreover, in SHRSP normalizing sodium intake after salt loadin g attenuates development of cerebral edema and reduces proteinuria.