Non-invasive Measurement of Cerebrovascular Reactivity After Traumatic Brain Injury

Cerebrovascular Reactivity Assessed With Functional Near-infrared Spectroscopy as a Biomarker of Traumatic Microvascular Injury After Moderate-severe Traumatic Brain Injury

The investigators will longitudinally measure cerebrovascular reactivity (CVR) by functional near-infrared spectroscopy (fNIRS) in acute (≤3 days from injury), subacute, and chronic phases after TBI as a biomarker of TCVI as compared to healthy controls. CVR will be measured by fNIRS response to hypercapnia. The investigators hypothesize that CVR will be decreased after TBI and that these decreases will correlate with clinical outcomes. Furthermore, the investigators predict that administration of a vasodilatory medication (sildenafil) will augment CVR after TBI.

Inclusion Criteria:

1. Men and women, aged ≥18

2. CT evidence of TBI-linked abnormality

   • Traumatic subarachnoid hemorrhage
   • Intracerebral hemorrhage/contusion
   • Subdural/epidural hematoma

3. Ability to undergo fNIRS testing with hypercapnia challenge

4. Subject able to provide informed consent

5. Attending of record agrees to include subject in study

Exclusion Criteria:

1. Unstable respiratory or hemodynamic status

2. Evidence of penetrating brain injury

3. TBI requiring craniotomy or craniectomy

4. Evidence or risk of ICP crisis

5. History of disabling pre-existing neurologic disorder (e.g. dementia, uncontrolled epilepsy, multiple sclerosis, strokes, brain tumors, prior severe TBI, or other disorder that confounds interpretation of NIRS testing or neuropsychological results)

6. History of pre-existing disabling mental illness (e.g. major depression or schizophrenia)

7. Exclusion criteria for sildenafil administration:

   • History of melanoma
   • current use of organic nitrate vasodilators
   • current use of ritonavir (HIV-protease inhibitor)
   • current use of erythromycin, ketoconazole, or itraconazole; current use of cimetidine
   • current use of alpha-blockers such as doxazosin (Cardura), tamsulosin (Flomax), and terazosin (Hytrin) prazosin (Minipres)
   • resting hypotension (systolic BP <90)
   • severe renal insufficiency
   • hepatic cirrhosis
   • acute ischemic stroke within past 2 months
   • acute myocardial infarction within past 2 months
   • unstable angina pectoris
   • acute or chronic heart failure
   • retinitis pigmentosa
   • pregnant or breastfeeding female
   • known hypersensitivity or allergy to sildenafil

8. Unstable cardiac status that constitutes a contraindication to sexual activity

9. Inability to read and communicate in English (necessary to obtain reliable neuropsychometric data)

10. Nursing mothers