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

Burwood, George W S / Dziennis, Suzan / Wilson, Teresa / Foster, Sarah / Zhang, Yuan / Liu, Gangjun / Yang, Jianlong / Elkins, Sean / Nuttall, Alfred L

Scientific reports

2020 Volume 10, Issue 1, Page(s) 9229

Abstract: 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 ...

Abstract	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. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. Therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.
MeSH term(s)	Acoustic Stimulation ; Animals ; Cadherins/genetics ; Cadherins/metabolism ; Cochlea/blood supply ; Cochlea/diagnostic imaging ; Cochlea/physiology ; Disease Models, Animal ; Hearing Loss, Noise-Induced/etiology ; Hearing Loss, Noise-Induced/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mutation ; Noise/adverse effects ; Regional Blood Flow/physiology ; Tomography, Optical Coherence
Chemical Substances	Cadherins ; Cdh23 protein, mouse
Language	English
Publishing date	2020-06-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-66192-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Macro-to-micro cortical vascular imaging underlies regional differences in ischemic brain.

Dziennis, Suzan / Qin, Jia / Shi, Lei / Wang, Ruikang K

Scientific reports

2015 Volume 5, Page(s) 10051

Abstract: 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 ... ...

Abstract	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. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.
MeSH term(s)	Angiography ; Animals ; Brain Infarction/complications ; Brain Infarction/pathology ; Brain Infarction/physiopathology ; Brain Ischemia/complications ; Brain Ischemia/diagnosis ; Brain Ischemia/pathology ; Brain Ischemia/physiopathology ; Capillaries/pathology ; Capillaries/physiopathology ; Cerebrovascular Circulation ; Contrast Media ; Diagnostic Imaging ; Hemoglobins/metabolism ; Infarction, Middle Cerebral Artery/complications ; Infarction, Middle Cerebral Artery/pathology ; Infarction, Middle Cerebral Artery/physiopathology ; Lasers ; Male ; Mice, Inbred C57BL ; Optical Imaging ; Oxygen/metabolism ; Reperfusion
Chemical Substances	Contrast Media ; Hemoglobins ; Oxygen (S88TT14065)
Language	English
Publishing date	2015-05-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep10051
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Article: Role of signal transducer and activator of transcription 3 in neuronal survival and regeneration.

Dziennis, Suzan / Alkayed, Nabil J

Reviews in the neurosciences

2008 Volume 19, Issue 4-5, Page(s) 341–361

Abstract: 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 ... ...

Abstract	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. We focus on STAT3 because of the expanding body of literature that investigates protective and regenerative effects of growth factors, hormones and cytokines that use STAT3 to mediate their effect, in part through transcriptional upregulation of neuroprotective and neurotrophic genes. Defining the endogenous molecular mechanisms that lead to neuroprotection by STAT3 after injury might identify novel therapeutic targets against acute neural tissue damage as well as chronic neurodegenerative disorders.
MeSH term(s)	Animals ; Cell Survival/drug effects ; Humans ; Nerve Regeneration/drug effects ; Nerve Regeneration/physiology ; Neurons/drug effects ; Neurons/physiology ; STAT3 Transcription Factor/genetics ; STAT3 Transcription Factor/metabolism ; STAT3 Transcription Factor/therapeutic use
Chemical Substances	STAT3 Transcription Factor
Language	English
Publishing date	2008-05-20
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	639035-3
ISSN	2191-0200 ; 0334-1763
ISSN (online)	2191-0200
ISSN	0334-1763
DOI	10.1515/revneuro.2008.19.4-5.341
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Article ; Online: Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography.

Yousefi, Siavash / Qin, Jia / Dziennis, Suzan / Wang, Ruikang K

Journal of biomedical optics

2014 Volume 19, Issue 7, Page(s) 76015

Abstract: 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 ... ...

Abstract	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. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies.
MeSH term(s)	Angiography/instrumentation ; Angiography/methods ; Animals ; Equipment Design ; Mice ; Mice, Hairless ; Microcirculation/physiology ; Skin/blood supply ; Tomography, Optical Coherence/instrumentation ; Tomography, Optical Coherence/methods ; Wound Healing/physiology
Language	English
Publishing date	2014-07-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.19.7.076015
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Article ; Online: The mechanoelectrical transducer channel is not required for regulation of cochlear blood flow during loud sound exposure in mice

George W. S. Burwood / Suzan Dziennis / Teresa Wilson / Sarah Foster / Yuan Zhang / Gangjun Liu / Jianlong Yang / Sean Elkins / Alfred L. Nuttall

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 11

Abstract: Abstract 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 ... ...

Abstract	Abstract 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. We hypothesize that genetic manipulation of the mechanoelectrical transducer complex will abolish sound induced cochlear blood flow regulation. We used salsa mice, a Chd23 mutant with no mechanoelectrical transduction, and deafness before p56. Using optical coherence tomography angiography, we measured the cochlear blood flow of salsa and wild-type mice in response to loud sound (120 dB SPL, 30 minutes low-pass filtered noise). An expected sound induced decrease in cochlear blood flow occurred in CBA/CaJ mice, but surprisingly the same sound protocol induced cochlear blood flow increases in salsa mice. Blood flow did not change in the contralateral ear. Disruption of the sympathetic nervous system partially abolished the observed wild-type blood flow decrease but not the salsa increase. Therefore sympathetic activation contributes to sound induced reduction of cochlear blood flow. Additionally a local, non-sensory pathway, potentially therapeutically targetable, must exist for cochlear blood flow regulation.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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

Qin, Jia / Reif, Roberto / Zhi, Zhongwei / Dziennis, Suzan / Wang, Ruikang

Biomedical optics express

2012 Volume 3, Issue 3, Page(s) 455–466

Abstract: 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- ... ...

Abstract	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). The OMAG system is used to acquire high resolution images of the functional blood vessel network. The vessel area density (VAD) is used to quantify the blood vessel network morphology, specifically the capillary recruitment. The proposed multi-functional system is employed to assess the blood perfusion status from a mouse pinna before and immediately after a burn injury. To our knowledge, this is the first non-invasive, non-contact and multifunctional imaging modality that can simultaneously measure variations of several blood perfusion parameters.
Language	English
Publishing date	2012-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085 ; 2156-7085
ISSN (online)	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.3.000455
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Article ; Online: External Compression Versus Intravascular Injection: A Mechanistic Animal Model of Filler-Induced Tissue Ischemia.

Chang, Shu-Hong / Yousefi, Sivash / Qin, Jia / Tarbet, Kristin / Dziennis, Suzan / Wang, Ruikang / Chappell, Michael C

Ophthalmic plastic and reconstructive surgery

2016 Volume 32, Issue 4, Page(s) 261–266

Abstract: 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 ...

Abstract	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. Methods: To determine the effect of external vascular compression on distal perfusion, the authors attempted to occlude vessels with subcutaneous hyaluronic acid gel (HAG) bolus injections into the pinna of hairless mice. The authors also performed suture ligation of a major vascular bundle. Following these interventions, laser speckle and optical microangiography were performed serially over 1 week follow up. To determine the effect of intravascular HAG injection, the authors devised and validated a novel method of cannulating the mouse external carotid artery for intraarterial access to the pinna vasculature. Using this model, the authors performed intraarterial HAG injections and completed optical microangiography and laser speckle contrast imaging. Results: Despite large HAG bolus injections directly adjacent to vascular bundles, the authors were unable to induce compressive occlusion of the mouse pinna vessels. Vascular occlusion was successfully performed with suture ligation, but optical microangiography and laser speckle contrast imaging confirmed undisturbed distal capillary bed perfusion. With intravascular HAG injection, large segments of pinna showed distinct perfusion reduction along a vascular distribution when compared with preinjection images, most noticeably at the capillary level. Conclusions: The novel mouse pinna model combining intravascular access and in vivo microvascular perfusion imaging has furthered the understanding of the mechanism of filler-induced tissue ischemia. Distal capillary perfusion was maintained despite external vascular compression. Intraarterial HAG filler injection, however, resulted in large areas of capillary nonperfusion and is the most likely etiology for filler-induced tissue necrosis that is observed clinically.
MeSH term(s)	Animals ; Cosmetic Techniques ; Dermal Fillers/administration & dosage ; Disease Models, Animal ; Hyaluronic Acid/administration & dosage ; Ischemia/physiopathology ; Ischemia/therapy ; Male ; Mice ; Mice, Hairless ; Regional Blood Flow ; Skin/blood supply
Chemical Substances	Dermal Fillers ; Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2016-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	632830-1
ISSN	1537-2677 ; 0740-9303
ISSN (online)	1537-2677
ISSN	0740-9303
DOI	10.1097/IOP.0000000000000484
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Article: Ciliary neurotrophic factor suppresses Phox2a in sympathetic neurons.

Dziennis, Suzan / Habecker, Beth A

Neuroreport

2004 Volume 15, Issue 1, Page(s) 33–36

Abstract: The cholinergic differentiation factor ciliary neurotrophic factor (CNTF) suppresses noradrenergic properties while inducing cholinergic and peptidergic properties in sympathetic neurons. In the rat, this includes suppression of the noradrenergic enzymes ...

Abstract	The cholinergic differentiation factor ciliary neurotrophic factor (CNTF) suppresses noradrenergic properties while inducing cholinergic and peptidergic properties in sympathetic neurons. In the rat, this includes suppression of the noradrenergic enzymes tyrosine hydroxylase and dopamine beta-hydroxylase. Lower enzyme levels result in part from suppression of gene transcription, but the mechanisms are unknown. We found that ciliary neurotrophic factor decreased the transcriptional activator Phox2a in neuroblastoma cells and cultured sympathetic neurons, suggesting that the loss of Phox2a is part of the mechanism by which CNTF suppresses tyrosine hydroxylase and dopamine beta-hydroxylase. Consistent with this model, Phox2a is suppressed in rat cholinergic sympathetic neurons where noradrenergic enzymes decrease, but is not altered in mouse cholinergic neurons where these enzymes remain high.
MeSH term(s)	Adrenergic Fibers/drug effects ; Adrenergic Fibers/metabolism ; Animals ; Cell Line, Tumor ; Cells, Cultured ; Ciliary Neurotrophic Factor/physiology ; Homeodomain Proteins/antagonists & inhibitors ; Homeodomain Proteins/biosynthesis ; Humans ; Nerve Tissue Proteins ; Rats ; Rats, Sprague-Dawley ; Superior Cervical Ganglion/drug effects ; Superior Cervical Ganglion/metabolism ; Transcription Factors/antagonists & inhibitors ; Transcription Factors/biosynthesis
Chemical Substances	Ciliary Neurotrophic Factor ; Homeodomain Proteins ; Nerve Tissue Proteins ; PHOX2A protein, human ; Phox2a protein, mouse ; Phox2a protein, rat ; Transcription Factors
Language	English
Publishing date	2004-01-19
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/00001756-200401190-00008
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Article ; Online: Responses of peripheral blood flow to acute hypoxia and hyperoxia as measured by optical microangiography.

Jia, Yali / Li, Peng / Dziennis, Suzan / Wang, Ruikang K

PloS one

2011 Volume 6, Issue 10, Page(s) e26802

Abstract: 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 ... ...

Abstract	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. In this paper, optical micro-angiography (OMAG) was employed that uses intrinsic optical scattering signals backscattered from blood flows for imaging PBF in skeletal muscle challenged by the alteration of oxygen concentration. By utilizing optical reflectance signals, we demonstrated that OMAG is able to show the response of hemodynamic activities upon acute hypoxia and hyperoxia, including the modulation of macrovascular caliber, microvascular density, and flux regulation within different sized vessels within skeletal muscle in mice in vivo. Our results suggest that OMAG is a promising tool for in vivo monitoring of functional macro- or micro-vascular responses within peripheral vascular beds.
MeSH term(s)	Angiography/methods ; Animals ; Diagnostic Imaging/methods ; Hemodynamics ; Hyperoxia/blood ; Hyperoxia/physiopathology ; Hypoxia/blood ; Hypoxia/physiopathology ; Light ; Mice ; Microcirculation ; Muscle, Skeletal/blood supply ; Oxygen/analysis ; Oxygen/blood ; Regional Blood Flow/physiology ; Scattering, Radiation
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2011-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0026802
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Reif, Roberto / Zhi, Zhongwei / Dziennis, Suzan / Nuttall, Alfred L / Wang, Ruikang K

Quantitative imaging in medicine and surgery

2013 Volume 3, Issue 5, Page(s) 235–242

Abstract: 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 ...

Abstract	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 ~1.5 mm radius) of tissue. Both systems determined that the blood flow within the cochlea is reduced due to the LSE stimulation.
Language	English
Publishing date	2013-11-05
Publishing country	China
Document type	Journal Article
ZDB-ID	2653586-5
ISSN	2223-4306 ; 2223-4292
ISSN (online)	2223-4306
ISSN	2223-4292
DOI	10.3978/j.issn.2223-4292.2013.10.02
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