Resting metabolic rate, abdominal fat pad and liver metabolic gene expression in female rats provided a snacking diet from weaning to adulthood.

Our female rat model with continuous, ad libitum access to snacks and chow from weaning to adulthood closely mimics human feeding behavior from childhood onwards. It causes weight gain, enlarged abdominal fat pads, reduced insulin sensitivity and leptin resistance without an increase in total caloric intake. Our current study investigated if this change in energy partitioning is due to a decrease in resting metabolic rate (RMR). In addition, we determined if carbohydrate and lipid metabolism changes in abdominal fat pads and liver. RMR, using indirect calorimetry, was determined in control and snacking rats every two weeks from Days 28-29 to Days 76-77. RMR decreased with age in both groups, but there was no difference between snacking and control rats at any age. At termination, abdominal fat pads (parametrial, retroperitoneal and mesenteric) and liver samples were collected for determination of gene expression for 21 genes involved in carbohydrate and lipid metabolism using RT-qPCR. Analysis of gene expression data showed a striking difference between metabolic profiles of control and snacking rats in abdominal fat pads and liver, with a distinct segregation of genes for both lipid and carbohydrate metabolism that correlated with an increase in body weight and fat pad weights. Genes involved in lipogenesis were upregulated in abdominal fat pads, while genes involved in adipogenesis, and lipid recycling were upregulated in the liver. In conclusion, snacking in addition to chow from weaning in female rats causes a repartitioning of energy that is not due to depressed RMR in snacking rats. Rather, snacking from weaning causes a shift in gene expression resulting in energy partitioning toward enhanced abdominal fat pad lipogenesis, and adipogenesis and lipid recycling in liver.

Prehospital Detection of Life-Threatening Intracranial Pathology: An Unmet Need for Severe TBI in Austere, Rural, and Remote Areas.

Severe traumatic brain injury (TBI) is a leading cause of death and disability worldwide, especially in low- and middle-income countries, and in austere, rural, and remote settings. The purpose of this Perspective is to challenge the notion that accurate and actionable diagnosis of the most severe brain injuries should be limited to physicians and other highly-trained specialists located at hospitals. Further, we aim to demonstrate that the great opportunity to improve severe TBI care is in the prehospital setting. Here, we discuss potential applications of prehospital diagnostics, including ultrasound and near-infrared spectroscopy (NIRS) for detection of life-threatening subdural and epidural hemorrhage, as well as monitoring of cerebral hemodynamics following severe TBI. Ultrasound-based methods for assessment of cerebrovascular hemodynamics, vasospasm, and intracranial pressure have substantial promise, but have been mainly used in hospital settings; substantial development will be required for prehospital optimization. Compared to ultrasound, NIRS is better suited to assess certain aspects of intracranial pathology and has a smaller form factor. Thus, NIRS is potentially closer to becoming a reliable method for non-invasive intracranial assessment and cerebral monitoring in the prehospital setting. While one current continuous wave NIRS-based device has been FDA-approved for detection of subdural and epidural hemorrhage, NIRS methods using frequency domain technology have greater potential to improve diagnosis and monitoring in the prehospital setting. In addition to better technology, advances in large animal models, provider training, and implementation science represent opportunities to accelerate progress in prehospital care for severe TBI in austere, rural, and remote areas.

Localization of cortical tissue optical changes during seizure activity in vivo with optical coherence tomography.

Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth-resolved cross-sectional images. In this study, OCT was used to detect changes in the optical properties of cortical tissue in vivo in mice during the induction of global (pentylenetetrazol) and focal (4-aminopyridine) seizures. Through the use of a confidence interval statistical method on depth-resolved volumes of attenuation coefficient, we demonstrated localization of regions exhibiting both significant positive and negative changes in attenuation coefficient, as well as differentiating between global and focal seizure propagation.

In vivo optical microscopy of peripheral nerve myelination with polarization sensitive-optical coherence tomography.

Assessing nerve integrity and myelination after injury is necessary to provide insight for treatment strategies aimed at restoring neuromuscular function. Currently, this is largely done with electrical analysis, which lacks direct quantitative information. In vivo optical imaging with sufficient imaging depth and resolution could be used to assess the nerve microarchitecture. In this study, we examine the use of polarization sensitive-optical coherence tomography (PS-OCT) to quantitatively assess the sciatic nerve microenvironment through measurements of birefringence after applying a nerve crush injury in a rat model. Initial loss of function and subsequent recovery were demonstrated by calculating the sciatic function index (SFI). We found that the PS-OCT phase retardation slope, which is proportional to birefringence, increased monotonically with the SFI. Additionally, histomorphometric analysis of the myelin thickness and g-ratio shows that the PS-OCT slope is a good indicator of myelin health and recovery after injury. These results demonstrate that PS-OCT is capable of providing nondestructive and quantitative assessment of nerve health after injury and shows promise for continued use both clinically and experimentally in neuroscience.

Decreased light attenuation in cerebral cortex during cerebral edema detected using optical coherence tomography.

Cerebral edema develops in response to a variety of conditions, including traumatic brain injury and stroke, and contributes to the poor prognosis associated with these injuries. This study examines the use of optical coherence tomography (OCT) for detecting cerebral edema in vivo. Three-dimensional imaging of an in vivo water intoxication model in mice was performed using a spectral-domain OCT system centered at 1300 nm. The change in attenuation coefficient was calculated and cerebral blood flow was analyzed using Doppler OCT techniques. We found that the average attenuation coefficient in the cerebral cortex decreased over time as edema progressed. The initial decrease began within minutes of inducing cerebral edema and a maximum decrease of 8% was observed by the end of the experiment. Additionally, cerebral blood flow slowed during late-stage edema. Analysis of local regions revealed the same trend at various locations in the brain, consistent with the global nature of the cerebral edema model used in this study. These results demonstrate that OCT is capable of detecting in vivo optical changes occurring due to cerebral edema and highlights the potential of OCT for precise spatiotemporal detection of cerebral edema.