Microvascular Injury and Blood-brain Barrier Dysfunction as Novel Biomarkers and Targets for Treatment in Traumatic Brain Injury

Microvascular Injury and Blood-brain Barrier Dysfunction as Novel Biomarkers and Targets for Treatment in Traumatic Brain Injury

Traumatic brain injury (TBI) is a leading cause of death and disability around the world. The social and economic burden of TBI is tremendous and the cost of TBI is estimated at $1 billion per year in Canada- $650 million in care and $580 million in lost productivity. Novel interventions aimed at TBI-linked molecular targets have been successful in limiting injury and improving neurologic recovery in animal models, thus providing compelling evidence that effective intervention is possible after injury. This study proposes to investigate traumatic microvascular injury (TMI) and specifically blood-brain barrier dysfunction (BBBD) as a candidate biomarker and therapeutic target in TBI.

Inclusion Criteria:

• Age 18 - 85 inclusive

• Clinically diagnosed TBI or evidence of TBI

• For mild TBI, as defined by the American Congress on Rehabilitation Medicine (1993), clear evidence and/or documentation of blunt head injury and any one of the following:

  • any loss of consciousness up to 30 min
  • any loss of memory for events immediately before or after the injury as much as 24 h
  • any alteration of mental state at the time of the injury
  • focal neurologic deficits that might or might not be transient

but where the severity of the injury does not exceed oss of consciousness exceeding 30 min, posttraumatic amnesia longer than 24 h, a Glasgow Coma Scale score falling below 13 after 30 min.

• For moderate TBI (GCS 9-12) and severe TBI (GCS 4-8) CT evidence of TBI-linked abnormality (intracranial lesion including traumatic SAH, contusion, extra-axial hematoma). For patients who are intubated, use best documented GCS within first 48 hours of injury.
• Stable respiratory or hemodynamic status allowing MRI within 2-4 days of TBI as determined by the attending physician
• Patient or substitute decision maker can provide consent

Exclusion Criteria:

• Pre-existing known neurologic, psychiatric disease (dementia, prior severe TBI, schizophrenia, uncontrolled epilepsy, major depressive disorder, stroke, multiple sclerosis, brain tumor)
• Serious infection, complications (sepsis, multilobe pneumonia, etc.) < 4 days after TBI
• Acute ischemic heart disease (MI or unstable angina)
• SBP < 100 mm Hg, DBP < 60 mm Hg
• MRI contraindications; patient has metal implant, pacemaker, biostimulator, neurostimulator, internal defibrillator, history of metal in eye, inner ear implant, cerebral aneurism clip, joint replacement, any known metal in their body, or are pregnant or breast feeding
• History or evidence of active malignancy
• History or evidence of serious kidney (GFR =<60) , heart, or liver disease
• Pregnant or breast-feeding women
• Inability to complete follow up visits (e.g. tourists)