Blood-brain barrier permeability, cerebral edema, and neurologic function after closed head injury in rats

Y. Shapira, D. Setton, A. A. Artru, E. Shohami

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132 Scopus citations


We previously described the time course of changes in neurologic status (as indicated by neurologic severity score [NSS]) and cerebral edema (as indicated by brain tissue specific gravity and water content) after closed head trauma in rats. The present study was designed to determine whether head trauma alters the integrity of the blood-brain barrier (BBB), the role of the BBB in edema formation and neurologic outcome, and the effect of MK-801 (a noncompetitive N-methyl-D-aspartate receptor antagonist) on BBB permeability. Rats in which cranial impact was delivered during ether anesthesia (n = 106) were killed at 15 min, 1, 2, 4, 10, and 24 h, and 2, 4, and 7 days. Control rats (n = 12) received no cranial impact. Subsets of head-injured rats killed at 4 and 24 h received MK-801 (3 mg/kg intraperitoneally) 1 h after injury. BBB permeability was assessed with intravenous injection of Evans Blue dye, cerebral edema was assessed by determining brain tissue specific gravity and water content, and neurologic status was assessed using NSS. Tissue extravasation of Evans Blue was maximal in the injured hemisphere 4 h after injury, but a residual BBB permeability defect was still evident as long as 4 days after the insult. In MK-801-treated rats, extravasation of Evans Blue in the injured hemisphere was not significantly different from that in the noninjured hemisphere. The time course of alteration of BBB permeability differed from that of cerebral edema (which was maximal at 24 h and then gradually resolved by 4-7 days) and from NSS (which was maximal at 1 h after injury, then decreased toward preinjury values at 10 h postinjury and thereafter). Our results indicate that this model of closed head trauma causes increased BBB permeability to Evans Blue and that the changes in BBB are not directly, temporally related to cerebral edema or NSS. Treatment with MK-801 did not prevent increased BBB permeability at 4 and 24 h after injury.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalAnesthesia and Analgesia
Issue number1
StatePublished - 1 Jan 1993
Externally publishedYes


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