Head injury is still a leading cause of death and disability despite the implementation of aggressive methods of evaluation and treatment. To further improve outcome, effort must now be directed at the basic pathophysiologic processes involved. This project seeks to elucidate the pathophysiology of two secondary insults associated with severe head injury that are linked to poor outcome: 1. Cerebral ischemia, early (within the first 6 hours) after injury, and focal ischemia in later stages, and 2. The role of increased cerebral blood volume (CBV) in increasing intracranial pressure (ICP) or """"""""brain stiffness"""""""". To date, only a trend suggesting that ischemia occurs early after injury has been found, as measurements with 133Xe made in the Intensive Care Unit could not be performed early enough to confirm this suspicion. Accordingly, we propose to measure cerebral blood flow (CBF) as early as possible, using the stable Xenon enhanced CT technique, during the initial diagnostic CT scan of the patient. To investigate ongoing (focal) ischemia, follow-up Xe-CT CBF studies will be done on subsequent days. Regional CBF so obtained, will be related to clinical condition (GCS), CT findings, and outcome. Similar to the problems associated with early CBF studies, determinations of CBV in both normal and head-injured patients also have been cumbersome to date, but a recently developed technique enables fast measurement of CBV during the initial CT scan and at any ensuing CT scan. Following measurement of CBF with the stable Xenon CT method, mean transit time (MTT) and CBV will be determined in the same session, using dynamic CT scanning following an i.v. bolus of iodine contrast. CBV will be correlated with ICP and a measure of brain stiffness, the pressure-volume-index (PVI). Additionally, in the same patient population considered above, the influence of vascular factors upon ICP and PVI will be investigated by correlating responses of these parameters to blood pressure changes in patients with intact or defective autoregulation of CBF. The latter will be determined in the Intensive Care Unit by repeated measurements of CBF, using the 133Xe-method, and CMRO2, during manipulations of blood pressure. The successful conduct of this study will provide important information in an area for which little data exists. More importantly, the results of these investigations should allow for the determination of those patients who will benefit from therapies to prevent ischemia (e.g. by induced hypertension, or mannitol therapy), while understanding of the pathophysiology of increased ICP and brain stiffness will lead to more rational therapy aimed at either reduce brain edema or cerebral vascular engorgement. We feel confident, that these improved treatment modalities will eventually contribute to better outcome.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Neurology A Study Section (NEUA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Virginia Commonwealth University
Schools of Medicine
United States
Zip Code
Ritter, A M; Muizelaar, J P; Barnes, T et al. (1999) Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries. Neurosurgery 44:941-8
Schroder, M L; Muizelaar, J P; Fatouros, P P et al. (1998) Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia. Neurosurgery 42:1276-80;discussion 1280-1
Muizelaar, J P; Fatouros, P P; Schroder, M L (1997) A new method for quantitative regional cerebral blood volume measurements using computed tomography. Stroke 28:1998-2005
Schroder, M L; Muizelaar, J P; Kuta, A J et al. (1996) Thresholds for cerebral ischemia after severe head injury: relationship with late CT findings and outcome. J Neurotrauma 13:17-23
Bouma, G J; Muizelaar, J P (1995) Cerebral blood flow in severe clinical head injury. New Horiz 3:384-94
Schroder, M L; Muizelaar, J P; Bullock, M R et al. (1995) Focal ischemia due to traumatic contusions documented by stable xenon-CT and ultrastructural studies. J Neurosurg 82:966-71
Schroder, M L; Muizelaar, J P; Kuta, A J (1994) Documented reversal of global ischemia immediately after removal of an acute subdural hematoma. Report of two cases. J Neurosurg 80:324-7
Muizelaar, J P; Schroder, M L (1994) Overview of monitoring of cerebral blood flow and metabolism after severe head injury. Can J Neurol Sci 21:S6-11
Muizelaar, J P (1993) Cerebral ischemia-reperfusion injury after severe head injury and its possible treatment with polyethyleneglycol-superoxide dismutase. Ann Emerg Med 22:1014-21