Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury

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Object. It is well established that posttraumatic secondary ischemia contributes to poor outcome. Ion dysfunction leading to cytotoxic edema is a primary force in the formation of ischemic brain edema and is a principal component of traumatic brain swelling. Because cell swelling is the result of net ion and water movement, it is crucial to have a thorough understanding of these transient phenomena. The purpose of this study was to characterize the effects of secondary ischemia following traumatic brain injury (TBI) on the ability to restore ion homeostasis.

Methods. Twenty-four Sprague—Dawley rats were divided into four groups of six animals each. The rats underwent transient forebrain ischemia via bilateral carotid artery occlusion combined with hypotension: 15 minutes of forebrain ischemia (Group 1); 60 minutes of forebrain ischemia (Group 2); impact acceleration/TBI (Group 3); and impact acceleration/TBI followed by 15 minutes of ischemia (Group 4).

Ischemia resulted in a rapid accumulation of [K+]e: 41.94 ± 13.65 and 66.33 ± 6.63 mM, respectively, in Groups 1 and 2, with a concomitant decrease of [Na+]e: 64 ± 18 mM and 72 ± 11 mM in Groups 1 and 2. Traumatic brain injury resulted in a less severe although identical trend in ion dysfunction ([K+]e 30.42 ± 11.67 mM and [Na+]e 63 ± 33 mM). Secondary ischemia resulted in prolonged and sustained ion dysfunction with a concomitant elevation of intracranial pressure (ICP).

Conclusions. Analysis of these results indicates that ischemia and TBI are sublethal in isolation; however, when TBI is associated with secondary ischemia, ion dysfunction is sustained and is associated with elevated ICP.

Article Information

Address reprint requests to: Anthony Marmarou, Ph.D., Department of Neurosurgery, Virginia Commonwealth University, P.O. Box 980508, 1001 East Broad Street, Old City Hall, Suite 235, Richmond, Virginia 23298–0508. email:

© AANS, except where prohibited by US copyright law.



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    Graph depicting data obtained in Group 1. Note the changes in MABP, ICP, [Na+]e, and [K+]e during ischemia—reperfusion. Mean data are presented ± SDs.

  • View in gallery

    Graph demonstrating data obtained in Group 2. Note the changes in MABP, ICP, [Na+]e, and [K+]e during ischemia—reperfusion. Mean data are presented ± SDs.

  • View in gallery

    Graph depicting data obtained in Group 3. Note the changes in MABP, ICP, [Na+]e, and [K+]e. Mean data are presented ± SDs.

  • View in gallery

    Graph showing data obtained in Group 4. Note the changes in MABP, ICP, [Na+]e, and [K+]e following TBI and secondary ischemic injury. Mean data are presented ± SDs.



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