Proteomics of Brain Trauma-associated Elevated Intracranial Pressure (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 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.

Consenting healthy volunteers, head trauma, mild head trauma or acute orthopedic injury patients meeting enrollment criteria listed below.

• Brain Injuries, Traumatic
• Traumatic Brain Injury

• 1 healthy volunteers
  Healthy volunteers to act as controls
  Intervention: Other: Blood/saliva samples for protein/molecular analysis
• 2 head trauma
  Head trauma patients meeting enrollment criteria
  Intervention: Other: Blood/saliva samples for protein/molecular analysis
• 3 orthopedic injury

  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
  Intervention: Other: Blood/saliva samples for protein/molecular analysis
• 4 Mild TBI

  The mild TBI patients will be defined as those admitted to the ED 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
  Intervention: Other: Blood/saliva samples for protein/molecular analysis

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

• TIRR/Mission Connect
• The Center for Clinical and Translational Sciences (CCTS) Clinical Research Unit at The University of Texas Health Science Center at Houston