bioRxiv ScienceSearch

Biology subjects

Wilson, R. H.

Publications and source records attributed to Wilson, R. H..

3 recordsLinked to original sources

Cerebral perfusion and metabolism coupling during a critical time window provides rapid assessment of cardiac arrest severity and prognosis in a preclinical model

Improved quantitative understanding of the dynamic relationship among cerebral blood flow, oxygen consumption, and electrical activity is important to clinicians treating acute brain injury. Such knowledge would elucidate the neurovascular response to ischemia, helping to potentially guide treatment. Using a multimodal optical imaging platform and a clinically-relevant rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR), we continuously measured cerebral blood flow (CBF), brain tissue oxygenation (StO2), cerebral metabolic rate of oxygen (CMRO2), and cerebral electrical activity (electrocorticography; ECoG). Multiple phases of cerebral hemodynamic recovery, with different degrees of mismatch between CBF and CMRO2, were observed following CPR. At 1 min post-resuscitation, we observed that the ratio CBF/CMRO2 is indicative of CA duration/severity and prognostic (with 87% accuracy) of short-term neurological recovery measured by the re-initiation of ECoG activity. These measurements provide the earliest known metrics for assessment of CA severity and prognosis post-CPR. Interestingly, the accuracy of this information is lost beyond 2-3 minutes post-CPR, highlighting a critical, easily overlooked, period immediately post-CPR. These metrics do not require pre-resuscitation data, underscoring translational potential in emergency-response settings when pre-CA information is unavailable. These metrics encourage validation in human studies, potentially offering real-time feedback during CA/CPR to optimize neurological outcome.

neuroscience

Spreading depolarization and repolarization during cardiac arrest as an ultra-early marker of neurological recovery in a preclinical model

Spreading depolarization (SD) accompanies numerous neurological conditions, including migraine, stroke, and traumatic brain injury. There is significant interest in understanding the relationship between SD and neuronal injury. However, characteristics underlying SD and repolarization (RP) induced by global cerebral ischemia (e.g., cardiac arrest (CA)) and reperfusion are not well understood. Quantifying features of SD and RP during CA and cardiopulmonary resuscitation (CPR) may provide important metrics for diagnosis and prognosis of neurological injury from hypoxia-ischemia. We characterized SD and RP in a rodent model of asphyxial CA+CPR using a multimodal platform including electrocorticography (ECoG) and optical imaging. We detected SD and RP by (1) alternating current (AC), (2) direct current (DC), and (3) optical imaging of spreading ischemia, spreading edema, and vasoconstriction. Earlier SD (r=-0.80; p<0.001) and earlier RP (r=-0.71, p<0.001) were associated with better neurological recovery after 24hrs. SD+RP onset times predicted good vs poor neurological recovery with 82% sensitivity and 91% specificity. To our knowledge, this is the first preclinical study to link SD and RP characteristics with neurological recovery post-CA. These data suggest that SD and RP may be ultra-early, real-time prognostic markers of post-CA outcome, meriting further investigation into translational implications during global cerebral ischemia.

neuroscience

High-speed quantitative optical imaging of absolute metabolism in the rat cortex

Quantitative measures of blood flow and metabolism are essential for improved assessment of brain health and response to ischemic injury. In this report, we demonstrate a multimodal technique for measuring the cerebral metabolic rate of oxygen (CMRO2) in the rodent brain on an absolute scale (M O2 / min). We use laser speckle imaging (LSI) at 809 nm and spatial frequency domain imaging (SFDI) at 655 nm, 730 nm, and 850 nm to obtain spatiotemporal maps of cerebral blood flow (CBF), tissue absorption (a), and tissue scattering (s). Knowledge of these three values enables calculation of a characteristic blood flow speed, which in turn is input to a mathematical model with a \"zero-flow\" boundary condition to calculate absolute CMRO2. We apply this method to a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation. With this model, the zero-flow condition occurs during entry into CA. The CMRO2 values calculated with our method are in good agreement with those measured with magnetic resonance (MR) and positron emission tomography (PET) by other groups. Our technique provides a quantitative metric of cerebral metabolism that can potentially be used for comparison between animals and longitudinal monitoring of a single animal over multiple days, to assess differences in baseline metabolism and track recovery of metabolism in survival studies following ischemia and reperfusion.

neuroscience