The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice.

The mammalian cochlea possesses unique acoustic sensitivity due to a mechanoelectrical 'amplifier', which requires the metabolic support of the cochlear lateral wall. Loud sound exposure sufficient to induce permanent hearing damage causes cochlear blood flow reduction, which may contribute to hearing loss. However, sensory epithelium involvement in the cochlear blood flow regulation pathway is not fully described.

External Compression Versus Intravascular Injection: A Mechanistic Animal Model of Filler-Induced Tissue Ischemia.

Purpose: Soft tissue ischemia is a devastating and unpredictable complication following dermal filler injection. Multiple mechanisms to explain this complication have been proposed, including vascular compression, vessel damage, and intraarterial filler emboli. To elucidate the mechanism of injury, the authors introduce a mouse model, imaged with optical microangiography and laser speckle contrast imaging technologies, to demonstrate in vivo microvascular response to soft tissue and intravascular filler injection.

Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain.

The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia.

Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography.

Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques.

Changes in cochlear blood flow in mice due to loud sound exposure measured with Doppler optical microangiography and laser Doppler flowmetry.

In this work we determined the contributions of loud sound exposure (LSE) on cochlear blood flow (CoBF) in an in vivo anesthetized mouse model. A broadband noise system (20 kHz bandwidth) with an intensity of 119 dB SPL, was used for a period of one hour to produce a loud sound stimulus. Two techniques were used to study the changes in blood flow, a Doppler optical microangiography (DOMAG) system; which can measure the blood flow within individual cochlear vessels, and a laser Doppler flowmetry (LDF) system; which averages the blood flow within a volume (a hemisphere of ~1.

Tracking dynamic microvascular changes during healing after complete biopsy punch on the mouse pinna using optical microangiography.

Optical microangiography (OMAG) and Doppler optical microangiography (DOMAG) are two non-invasive techniques capable of determining the tissue microstructural content, microvasculature angiography, and blood flow velocity and direction. These techniques were used to visualize the acute and chronic microvascular and tissue responses upon an injury in vivo. A tissue wound was induced using a 0.

Monitoring hypoxia induced changes in cochlear blood flow and hemoglobin concentration using a combined dual-wavelength laser speckle contrast imaging and Doppler optical microangiography system.

A synchronized dual-wavelength laser speckle contrast imaging (DWLSCI) system and a Doppler optical microangiography (DOMAG) system was developed to determine several ischemic parameters in the cochlea due to a systemic hypoxic challenge. DWLSCI can obtain two-dimensional data, and was used to determine the relative changes in cochlear blood flow, and change in the concentrations of oxyhemoglobin (HbO), deoxyhemoglobin (Hb) and total hemoglobin (HbT) in mice. DOMAG can obtain three-dimensional data, and was used to determine the changes in cochlear blood flow with single vessel resolution.

Effects of hypoxia on cochlear blood flow in mice evaluated using Doppler optical microangiography.

Reduced cochlear blood flow (CoBF) is a main contributor to hearing loss. Studying CoBF has remained a challenge due to the lack of available tools. Doppler optical microangiography (DOMAG), a method to quantify single-vessel absolute blood flow, and laser Doppler flowmetry (LDF), a method for measuring the relative blood flow within a large volume of tissue, were used for determining the changes in CoBF due to systemic hypoxia in mice.

Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice.

We present a novel application of optical microangiography (OMAG) imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able to provide true capillary level imaging of the retinal and choroidal vasculature.

Fast synchronized dual-wavelength laser speckle imaging system for monitoring hemodynamic changes in a stroke mouse model.

In this Letter, we describe a newly developed synchronized dual-wavelength laser speckle contrast imaging system, which contains two cameras that are synchronously triggered to acquire data. The system can acquire data at a high spatiotemporal resolution (up to 500 Hz for ~1000×1000 pixels). A mouse model of stroke is used to demonstrate the capability for imaging the fast changes (within tens of milliseconds) in oxygenated and deoxygenated hemoglobin concentration, and the relative changes in blood flow in the mouse brain, through an intact cranium.

Quantifying optical microangiography images obtained from a spectral domain optical coherence tomography system.

The blood vessel morphology is known to correlate with several diseases, such as cancer, and is important for describing several tissue physiological processes, like angiogenesis. Therefore, a quantitative method for characterizing the angiography obtained from medical images would have several clinical applications. Optical microangiography (OMAG) is a method for obtaining three-dimensional images of blood vessels within a volume of tissue.

Hemodynamic and morphological vasculature response to a burn monitored using a combined dual-wavelength laser speckle and optical microangiography imaging system.

A multi-functional imaging system capable of determining relative changes in blood flow, hemoglobin concentration, and morphological features of the blood vasculature is demonstrated. The system combines two non-invasive imaging techniques, a dual-wavelength laser speckle contrast imaging (2-LSI) and an optical microangiography (OMAG) system. 2-LSI is used to monitor the changes in the dynamic blood flow and the changes in the concentration of oxygenated (HbO), deoxygenated (Hb) and total hemoglobin (HbT).

Responses of peripheral blood flow to acute hypoxia and hyperoxia as measured by optical microangiography.

Oxygen availability is regarded as a critical factor to metabolically regulate systemic blood flow. There is a debate as to how peripheral blood flow (PBF) is affected and modulated during hypoxia and hyperoxia; however in vivo evaluating of functional PBF under oxygen-related physiological perturbation remains challenging. Microscopic observation, the current frequently used imaging modality for PBF characterization often involves the use of exogenous contrast agents, which would inevitably perturb the intrinsic physiologic responses of microcirculation being investigated.

Recombinant T cell receptor ligands improve outcome after experimental cerebral ischemia.

A key target for novel stroke therapy is the regulation of post-ischemic inflammatory mechanisms. Recent evidence emphasizes the role of T lymphocytes of differing subtypes in the evolution is ischemic brain damage. We have recently demonstrated the benefit of myelin antigen-specific immunodulatory agents known as recombinant T cell receptor ligands (RTLs) in a standard murine model of focal stroke.

Regulatory B cells limit CNS inflammation and neurologic deficits in murine experimental stroke.

Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient μMT(-/-) mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated μMT(-/-) versus WT mice.

Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.

Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO).

Role of dihydrotestosterone in post-stroke peripheral immunosuppression after cerebral ischemia.

Stroke is a sexually dimorphic disease with male gender considered a disadvantage in terms of risk and disease outcome. In intact males, stroke induces peripheral immunosuppression, characterized by decreased splenocyte numbers and proliferation and altered percentages of viable T, B, and CD11b+ cells. To investigate whether the potent androgen and known immunomodulator, dihydrotestosterone (DHT), exacerbates post-stroke immunosuppression in castrated male mice after focal stroke, we evaluated the effect of middle cerebral artery occlusion (MCAO) on peripheral and central nervous system (CNS) immune responses in castrated mice with or without controlled levels of DHT.

Involvement of Stat3 in mouse brain development and sexual dimorphism: a proteomics approach.

Although the role of STAT3 in cell physiology and tissue development has been largely investigated, its involvement in the development and maintenance of nervous tissue and in the mechanisms of neuroprotection is not yet known. The potentially wide range of STAT3 activities raises the question of tissue- and gender-specificity as putative mechanisms of regulation. To explore the function of STAT3 in the brain and the hypothesis of a gender-linked modulation of STAT3, we analyzed a neuron-specific STAT3 knockout mouse model investigating the influence of STAT3 activity in brain protein expression pattern in both males and females in the absence of neurological insult.

Estradiol and G1 reduce infarct size and improve immunosuppression after experimental stroke.

Reduced risk and severity of stroke in adult females is thought to depend on normal endogenous levels of estrogen, a well-known neuroprotectant and immunomodulator. In male mice, experimental stroke induces immunosuppression of the peripheral immune system, characterized by a reduction in spleen size and cell numbers and decreased cytokine and chemokine expression. However, stroke-induced immunosuppression has not been evaluated in female mice.

Mechanisms of gender-linked ischemic brain injury.

Biological sex is an important determinant of stroke risk and outcome. Women are protected from cerebrovascular disease relative to men, an observation commonly attributed to the protective effect of female sex hormones, estrogen and progesterone. However, sex differences in brain injury persist well beyond the menopause and can be found in the pediatric population, suggesting that the effects of reproductive steroids may not completely explain sexual dimorphism in stroke.

Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration.

Signal Transducers and Activators of Transcription (STATs) comprise a family of transcription factors that mediate a wide variety of biological functions in the central and peripheral nervous systems. Injury to neural tissue induces STAT activation, and STATs are increasingly recognized for their role in neuronal survival. In this review, we discuss the role of STAT3 during neural development and following ischemic and traumatic injury in brain, spinal cord and peripheral nerves.

Developmental exposure to polychlorinated biphenyls influences stroke outcome in adult rats.

Background: The "developmental origins of adult disease" hypothesis was originally derived from evidence linking low birth weight to cardiovascular diseases including stroke. Subsequently, it has been expanded to include developmental exposures to environmental contaminants as risk factors for adult onset disease.

Objective: Our goal in this study was to test the hypothesis that developmental exposure to poly-chlorinated biphenyls (PCBs) alters stroke outcome in adults.

Role of signal transducer and activator of transcription-3 in estradiol-mediated neuroprotection.

Estradiol is protective in experimental cerebral ischemia, but the precise mechanisms remain unknown. Signal transducer and activator of transcription-3 (STAT3) is a transcription factor that is activated by estrogen, translocates to the nucleus, and induces the transcription of neuroprotective genes, such as bcl-2. We determined whether estradiol increases STAT3 activation in female rat brain after focal cerebral ischemia and whether STAT3 activation contributes to estradiol-mediated neuroprotection against ischemic brain injury.

ERK1/2 is a negative regulator of homeodomain protein Arix/Phox2a.

The homeodomain protein Arix/Phox2a plays a role in the development and maintenance of the noradrenergic cell type by regulating the transcription of genes involved in the biosynthesis and metabolism of noradrenaline. Previous work has shown that Arix/Phox2a is a phosphoprotein, and the phosphorylated form of Arix/Phox2a exhibits poorer DNA-binding activity than does the dephosphorylated form. Here, we demonstrate that Arix/Phox2a is phosphorylated by extracellular signal-related kinase (ERK)1/2 at two sites within the N-terminal transactivation domain.

Age and diet act through distinct isoforms of the class II transactivator gene in mouse intestinal epithelium.

Background & Aims: Normal weaning induces class II major histocompatibility complex (Ia) and invariant chain (Ii) expression in the mouse intestinal epithelium. Because the class II transactivator protein (CIITA) induces Ia and Ii in most cell types, we hypothesized that diet-induced expression of these genes was through CIITA.

Methods: Mouse litters were split and weaned onto an elemental diet or a normal (complex) chow diet.