Proteomics of Brain Trauma-associated Elevated Intracranial Pressure (ICP)

One of the major causes of death following brain trauma is increased intracranial pressure
(ICP). Currently, there are no effective ways to predict if the ICP of a patient will reach
uncontrollable levels. Various cytokines (balance between pro-and anti-inflammatory) and
other factors are thought to underlie increases in ICP. The specific aim of this research is
to determine if the blood from brain-injured patients contains reproducible protein markers
that appear prior to elevations in ICP. We propose to employ mass spectrometry, antibody
array and ELISA to profile proteins in the serum of patients suffering from traumatic brain
injury. These protein profiles will be compiled by a pattern recognition program that has the
capacity to learn and make predictions based on the spectra and associated patient
information. Each time a sample is analyzed, it is added to the database allowing the program
to make increasingly accurate predictions. Protein profiles of patients with known ICP values
will be analyzed. Our hypothesis is that alterations in serum protein composition will
precede changes in intracranial pressure giving rise to predictable patterns that can be
detected using large-scale proteomic analysis. After approximately 90 non-brain trauma and 90
brain-trauma patients are analyzed, if markers are found, the predictability of elevated ICP
will be tested. If successful, this may aid the neurosurgeon in determining future courses of
treatment.

Inclusion Criteria:

- 14-65 years old

- Non-penetrating brain injury

- ICP monitor or

- Healthy volunteer or

The orthopedic injury cohort will include patients admitted to the ED able to provide
informed consent with the following:

1. Fracture confirmed radiographically

2. No head trauma

3. No other known inflammatory process or infection

4. No history of neurological or psychiatric disorders or alcohol or drug dependency.

or The mild TBI patients will be defined as those experiencing,

1. Non-penetrating head trauma manifesting one or more of the following:

- Loss of consciousness

- Post-traumatic amnesia

- Altered mental status

- Focal neurologic deficits, seizure

2. GCS> 12

3. No abnormalities on CT other than contusion

4. No operative Lesions

5. Length of hospital stay < 48 hrs

6. No other known inflammatory process or infection

7. No history of neurological or psychiatric disorders or alcohol or drug dependency

Exclusion Criteria:

- Inability to obtain informed consent