Stroke, Vol 21, 1210-1214, Copyright © 1990 by American Heart Association
DJ Mujsce, J Towfighi, D Stern and RC Vannucci
To study the efficacy of mannitol in reducing cerebral edema and improving
the ultimate neuropathologic outcome in perinatal cerebral
hypoxia-ischemia, 67 7-day postnatal rats were subjected to unilateral
common carotid artery ligation followed by exposure to 8% oxygen at 37
degrees C for 3 hours. Twenty-seven rat pups received a subcutaneous
injection of 0.1 ml mannitol in a dosage of 4 mg/kg body wt immediately
following cerebral hypoxia-ischemia and every 12 hours thereafter for a
total of four doses. Control animals received either no therapy (n = 16) or
an equivalent volume of normal saline (n = 24). Mannitol injections in six
rat pups not subjected to hypoxia-ischemia produced no mortality but
significantly increased serum osmolality from 287 to 361 mos/l (p less than
0.01). Preliminary studies indicated that substantial mortality occurred
when greater doses of mannitol were administered to rats. After 48 hours of
recovery from hypoxia-ischemia, the animals were killed and their brains
were examined for either tissue water content (33 rat pups) or the presence
of neuropathologic alterations (34 rat pups). Mannitol significantly
reduced (p less than 0.001) brain water content, as a reflection of
cerebral edema, in both the ipsilateral (88.5% compared with 90.6% in
controls) and the contralateral (85.0% compared with 87.2% in controls)
cerebral hemispheres. Mannitol therapy did not ameliorate the incidence,
distribution, or severity of tissue injury in the cerebral cortex,
subcortical white matter, hippocampus, striatum, or thalamus of the
ipsilateral cerebral hemisphere compared with the controls. Thus, while
mannitol substantially reduces the extent of cerebral edema following
hypoxia-ischemia, no beneficial affect on ultimate brain damage
occurs.(ABSTRACT TRUNCATED AT 250 WORDS)
ARTICLES
Mannitol therapy in perinatal hypoxic-ischemic brain damage in rats
Departments of Pediatrics, Neonatology, Pennsylvania State University School of Medicine, Milton S. Hershey Medical Center, Hershey 17033.
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