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1.  Early Cerebral Perfusion Pressure Augmentation with Phenylephrine after Traumatic Brain Injury may be Neuroprotective in a Pediatric Swine Model 
Critical Care Medicine  2012;40(8):2400-2406.
Objective
Cerebral perfusion pressure (CPP) less than 40 mm Hg following pediatric traumatic brain injury (TBI) has been associated with increased mortality independent of age, and current guidelines recommend maintaining CPP between 40–60 mm Hg. Although adult TBI studies have observed an increased risk of complications associated with targeting a CPP > 70, we hypothesize that targeting a CPP of 70 mm Hg with the use of phenylephrine early after injury in the immature brain will be neuroprotective.
Design
Animals were randomly assigned to injury with CPP = 70 mm Hg (CPP70) or CPP = 40 mm Hg (CPP40). Diffuse TBI was produced by a single rapid rotation of the head in the axial plane. Cerebral microdialysis, brain tissue oxygen, intracranial pressure, and cerebral blood flow (CBF) were measured 30 min – 6 h post-injury. One hour after injury, CPP was manipulated with the vasoconstrictor phenylephrine. Animals were euthanized 6 h post-TBI, brains fixed, and stained to assess regions of cell injury and axonal dysfunction.
Setting
University center.
Subject
21 four week-old female swine.
Measurements and Main Results
Augmentation of CPP to 70 mm Hg resulted in no change in axonal dysfunction, but significantly smaller cell injury volumes at 6 hours post injury compared to CPP40 (1.1% vs. 7.4%, p < 0.05). Microdialysis lactate/pyruvate ratios were improved at CPP70 compared to CPP40. CBF was higher in the CPP70 group but did not reach statistical significance. Phenylephrine was well tolerated and there were no observed increases in serum lactate or intracranial pressure in either group.
Conclusions
Targeting a CPP of 70 mm Hg resulted in a greater reduction in metabolic crisis and cell injury volumes compared to a CPP of 40 mm Hg in an immature swine model. Early aggressive CPP augmentation to a CPP of 70 mm Hg in pediatric TBI before severe intracranial hypertension has the potential to be neuroprotective, and further investigations are needed.
doi:10.1097/CCM.0b013e31825333e6
PMCID: PMC3400930  PMID: 22809910
pediatric head injury; cerebral perfusion pressure; phenylephrine; neuroprotection; swine; cerebral blood flow
2.  Evidence that a Panel of Neurodegeneration Biomarkers Predicts Vasospasm, Infarction, and Outcome in Aneurysmal Subarachnoid Hemorrhage 
PLoS ONE  2011;6(12):e28938.
Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6–9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H,
14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.
doi:10.1371/journal.pone.0028938
PMCID: PMC3235169  PMID: 22174930
3.  Noninvasive Measurement of Cerebral Blood Flow and Blood Oxygenation Using Near-Infrared and Diffuse Correlation Spectroscopies in Critically Brain-Injured Adults 
Neurocritical care  2010;12(2):173-180.
Background
This study assesses the utility of a hybrid optical instrument for noninvasive transcranial monitoring in the neurointensive care unit. The instrument is based on diffuse correlation spectroscopy (DCS) for measurement of cerebral blood flow (CBF), and near-infrared spectroscopy (NIRS) for measurement of oxy- and deoxy-hemoglobin concentration. DCS/NIRS measurements of CBF and oxygenation from frontal lobes are compared with concurrent xenon-enhanced computed tomography (XeCT) in patients during induced blood pressure changes and carbon dioxide arterial partial pressure variation.
Methods
Seven neurocritical care patients were included in the study. Relative CBF measured by DCS (rCBFDCS), and changes in oxy-hemoglobin (ΔHbO2), deoxy-hemoglobin (ΔHb), and total hemoglobin concentration (ΔTHC), measured by NIRS, were continuously monitored throughout XeCT during a baseline scan and a scan after intervention. CBF from XeCT regions-of-interest (ROIs) under the optical probes were used to calculate relative XeCT CBF (rCBFXeCT) and were then compared to rCBFDCS. Spearman’s rank coefficients were employed to test for associations between rCBFDCS and rCBFXeCT, as well as between rCBF from both modalities and NIRS parameters.
Results
rCBFDCS and rCBFXeCT showed good correlation (rs = 0.73, P = 0.010) across the patient cohort. Moderate correlations between rCBFDCS and ΔHbO2/ΔTHC were also observed. Both NIRS and DCS distinguished the effects of xenon inhalation on CBF, which varied among the patients.
Conclusions
DCS measurements of CBF and NIRS measurements of tissue blood oxygenation were successfully obtained in neurocritical care patients. The potential for DCS to provide continuous, noninvasive bedside monitoring for the purpose of CBF management and individualized care is demonstrated.
doi:10.1007/s12028-009-9305-x
PMCID: PMC2844468  PMID: 19908166
Near-infrared spectroscopy; Diffuse correlation spectroscopy; Cerebral blood flow; Xenon CT; Neurocritical care

Results 1-3 (3)