Mannitol therapy in perinatal hypoxic-ischemic brain damage in rats

Dennis J. Mujsce, Javad Towfighi, Diane Stern, Robert C. Vannucci

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30 Scopus citations


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° 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/1 (p<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<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 effect on ultimate brain damage occurs. Mannitol therapy affords little or no protection for the perinatal brain from hypoxic-ischemic damage.

Original languageEnglish (US)
Pages (from-to)1210-1214
Number of pages5
Issue number8
StatePublished - Aug 1990

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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