Experimental intracerebral hemorrhage: relationship between brain edema, blood flow, and blood-brain barrier permeability in rats

Guo-Yuan Yang M.D., Ph.D.1, A. Lorris Betz M.D., Ph.D.1, Thomas L. Chenevert Ph.D.1, James A. Brunberg M.D.1, and Julian T. Hoff M.D.1
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  • 1 Departments of Surgery (Neurosurgery), Pediatrics, Neurology, and Radiology, University of Michigan, Ann Arbor, Michigan
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✓ There have been few investigations of brain edema formation after intracerebral hemorrhage (ICH), despite the fact that mass effect and edema are important clinical complications. The present study was designed to investigate the time course for the formation and resolution of brain edema and to determine how changes in cerebral blood flow (CBF) and blood-brain barrier (BBB) permeability are temporally related to edema formation following ICH.

Anesthetized adult rats received a sterile injection of 100 µl of autologous blood into the caudate nucleus. Water and ion contents were measured immediately, at 4 and 12 hours, and daily to Day 7 (10 time points, six rats at each time) after experimental ICH. The water content of the ipsilateral basal ganglia increased progressively (p < 0.002) over the first 24 hours, then remained constant until after Day 5, when the edema began to resolve. Edema was most severe in the tissue immediately surrounding the hemorrhage; however, it was also present in the ipsilateral cortex, the contralateral cortex, and the basal ganglia. Measurements of local CBF (using [14C]-iodoantipyrine) and BBB permeability (using [3H]-α-aminoisobutyric acid) were obtained in separate groups of six to eight rats at various time intervals between 1 and 48 hours after ICH. Cerebral blood flow was reduced to 50% of control at 1 hour, returned to control values by 4 hours, but then decreased to less than 50% of control between 24 and 48 hours after ICH. The BBB permeability increased significantly prior to the occurrence of significant edema in the tissue surrounding the clot. However, BBB permeability in the more distant structures remained normal despite the development of edema.

These results demonstrate a time course for the formation and resolution of brain edema following ICH similar to that observed during focal ischemia. Brain edema forms in the immediate vicinity of the clot as a result of both BBB disruption and the local generation of osmotically active substances and then spreads to adjacent structures. While local ischemia, due to the mass effect of the hemorrhage, may play a role in producing cytotoxic and vasogenic edema, the release of toxic substances from the clot should also be considered. Since edema is nearly maximal by 24 hours after ICH, therapy directed at reducing edema formation must be instituted within the 1st day.

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