Physiology Commons^™

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Synthesis Of Rhamnosylated Arginine Glycopeptides And Determination Of The Glycosidic Linkage In Bacterial Elongation Factor P, Siyao Wang, Leo Corcilius, Phillip B. Sharp, Andrei Rajkovic, Michael Ibba, Benjamin L. Parker, Richard J. Payne

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

A new class of N-linked protein glycosylation – arginine rhamnosylation – has recently been discovered as a critical modification for the function of bacterial elongation factor P (EF-P). Herein, we describe the synthesis of suitably protected α- and β-rhamnosylated arginine amino acid “cassettes” that can be directly installed into rhamnosylated peptides. Preparation of a proteolytic fragment of Pseudomonas aeruginosa EF-P bearing both α- and β-rhamnosylated arginine enabled the unequivocal determination of the native glycosidic linkage to be α through 2D NMR and nano-UHPLC-tandem mass spectrometry studies.

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

Effects Of An 18- Week Strength, Conditioning, And Circuit Training Program On Weight Loss In A Middle Aged Adult Male, Aryeh D. Spingarn

Publications and Research

Aryeh Spingarn Queens College, City University of New York Department of Family, Nutrition, and Exercise Sciences, Effects of an 18-week strength, conditioning, and circuit training program on weight loss in a middle-aged male. Purpose: The purpose of this study was to examine the effects of a strength, conditioning, and circuit training program on weight loss in a middle age adult. Methods: The subject participated in an 18-week strength and conditioning program 2 days per week for one hour per session, totaling 2 hours of training time per week. The first 12 weeks of the program included only strength training for …

Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese

Pharmacology and Physiology Faculty Publications

No abstract provided.

The Complex Evolutionary History Of Aminoacyl-Trna Synthetases, Anargyros Chaliotis, Panayotis Vlastaridis, Dimitris Mossialos, Michael Ibba, Hubert D. Becker, Constantinos Stathopoulos, Grigorios D. Amoutzias

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Aminoacyl-tRNA synthetases (AARSs) are a superfamily of enzymes responsible for the faithful translation of the genetic code and have lately become a prominent target for synthetic biologists. Our large-scale analysis of >2500 prokaryotic genomes reveals the complex evolutionary history of these enzymes and their paralogs, in which horizontal gene transfer played an important role. These results show that a widespread belief in the evolutionary stability of this superfamily is misconceived. Although AlaRS, GlyRS, LeuRS, IleRS, ValRS are the most stable members of the family, GluRS, LysRS and CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent …

Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) elicits the production of superoxide (O2(•-)) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O2(•-) in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O2(•-) is causal in the development of AngII-induced hypertension, or if mitochondrial O2(•-) in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive. Herein, we hypothesized that increased mitochondrial O2(•-) in the absence of pro-hypertensive stimuli, such as AngII, elevates baseline systemic mean arterial …

Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey

Pharmacology and Physiology Faculty Publications

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially for …

Elucidating The Role Of Mifs-Mifr Two-Component System In Regulating Pseudomonas Aeruginosa Pathogenicity, Gorakh Digambar Tatke

FIU Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative, metabolically versatile, opportunistic pathogen that exhibits a multitude of virulence factors, and is extraordinarily resistant to a gamut of clinically significant antibiotics. This ability is in part mediated by two-component systems (TCS) that play a crucial role in regulating virulence mechanisms, metabolism and antibiotic resistance. Our sequence analysis of the P. aeruginosa PAO1 genome revealed the presence of two open reading frames, mifS and mifR, which encodes putative TCS proteins, a histidine sensor kinase MifS and a response regulator MifR, respectively. This two-gene operon was found immediately upstream of the poxAB operon, where poxB encodes …

Effects Of Target-Controlled Infusion Of High-Dose Naloxone On Pain And Hyperalgesia In A Human Thermal Injury Model: A Study Protocol, Anders D. Springborg, Elisabeth K. Jensen, Bradley K. Taylor, Mads U. Werner

Physiology Faculty Publications

Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion.

The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to …

Regulation Of Microvascular Flow And Metabolism: An Overview, Michelle A. Keske, Renee M. Dwyer, Ryan D. Russell, Sarah J. Blackwood, Aascha A. Brown, Donghua Hu, Dino Premilovac, Stephen M. Richards, Stephen Rattigan

Health & Human Performance Faculty Publications and Presentations

Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes. Either of these responses (myocyte and/or vascular) may be impaired …

Human Anatomy & Physiology Society ( Haps ) Southern Regional Meeting 2016, Cheryl Purvis

Faculty Proceedings, Presentations, Speeches and Lectures

No abstract provided.

Unusual Presentation Of A Young Man With Disseminated Tuberculosis And Right Ventricular Mass, Shahrukh Hashmani, Fateh Ali Tipoo Sultan, Muhammad Qamar Masood

Section of Cardiology

We report a 22-year-old man who presented to the emergency department with worsening shortness of breath and chronic fever for 2 months. Physical examination was unremarkable except for raised jugular venous pressure and palpable liver. Echocardiogram showed a large right ventricular mass causing obstruction at tricuspid valve. A subsequent chest CT scan confirmed the presence of a large mass in the right ventricle. There were multiple enlarged lymph nodes and consolidation in the right upper lobe. Diagnosis of disseminated tuberculosis(TB) was made and later confirmed by histopathology of lymph node biopsy along with positive sputum culture for acid-fast bacilli. Remarkable …

Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O2●-) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O2●- in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O2●- levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O2●- levels in response to …

Stable Engraftment Of Bifidobacterium Longum Ah1206 In The Human Gut Depends On Individualized Features Of The Resident Microbiome, María X. Maldonado-Gómez, Inés Martínez, Francesca Bottacini, Amy O’Callaghan, Marco Ventura, Douwe Van Sinderen, Benjamin Hillmann, Pajau Vangay, Dan Knights, Robert W. Hutkins, Jens Walter

Department of Food Science and Technology: Faculty Publications

Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. …

Neuromuscular Alterations After Ankle Sprains: An Animal Model To Establish Causal Links After Injury, Lindsey K. Lepley, Patrick O. Mckeon, Shane G. Fitzpatrick, Catherine L. Beckemeyer, Timothy L. Uhl, Timothy A. Butterfield

Physical Therapy Faculty Publications

Context: The mechanisms that contribute to the development of chronic ankle instability are not understood. Investigators have developed a hypothetical model in which neuromuscular alterations that stem from damaged ankle ligaments are thought to affect periarticular and proximal muscle activity. However, the retrospective nature of these studies does not allow a causal link to be established.

Objective: To assess temporal alterations in the activity of 2 periarticular muscles of the rat ankle and 2 proximal muscles of the rat hind limb after an ankle sprain.

Design: Controlled laboratory study.

Setting: Laboratory.

Patients or Other Participants: …

An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese

Pharmacology and Physiology Faculty Publications

Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop …

Effects Of Short‐Term Free‐Weight And Semi‐Block Periodization Resistance Training On Metabolic Syndrome, Mark A. South, Andrew S. Layne, N. Travis Triplett, William A. Sands, Satoshi Mizuguchi, W. Guy Hornsby, Ashley Kavanaugh, Michael H. Stone

ETSU Faculty Works

The effects of short-term resistance training on performance and health variables associated with prolonged sedentary lifestyle and metabolic syndrome (MS) were investigated. Resistance training may alter a number of health-related, physiological, and performance variables. As a result, resistance training can be used as a valuable tool in ameliorating the effects of a sedentary lifestyle including those associated with MS. Nineteen previously sedentary subjects (10 with MS and 9 with nonmetabolic syndrome [NMS]) underwent 8 weeks of supervised resistance training. Maximum strength was measured using an isometric midthigh pull and resulting force-time curve. Vertical jump height (JH) and power were measured …

Hypocretin/Orexin Peptides Alter Spike Encoding By Serotonergic Dorsal Raphe Neurons Through Two Distinct Mechanisms That Increase The Late Afterhyperpolarization, Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N. Ross, Christopher S. Leonard

NYMC Faculty Publications

Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), …

Cycle Training Modulates Satellite Cell And Transcriptional Responses To A Bout Of Resistance Exercise, Kevin A. Murach, R. Grace Walton, Christopher S. Fry, Sami L. Michaelis, Jason S. Groshong, Brian S. Finlin, Philip A. Kern, Charlotte A. Peterson

Physical Therapy Faculty Publications

This investigation evaluated whether moderate‐intensity cycle ergometer training affects satellite cell and molecular responses to acute maximal concentric/eccentric resistance exercise in middle‐aged women. Baseline and 72 h postresistance exercise vastus lateralis biopsies were obtained from seven healthy middle‐aged women (56 ± 5 years, BMI 26 ± 1, VO_2max 27 ± 4) before and after 12 weeks of cycle training. Myosin heavy chain (MyHC) I‐ and II‐associated satellite cell density and cross‐sectional area was determined via immunohistochemistry. Expression of 93 genes representative of the muscle‐remodeling environment was also measured via NanoString. Overall fiber size increased ~20% with cycle training ( …

Isoacceptor Specific Characterization Of Trna Aminoacylation And Misacylation In Vivo, Kyle Mohler, Rebecca Mann, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Amino acid misincorporation during protein synthesis occurs due to misacylation of tRNAs or defects in decoding at the ribosome. While misincorporation of amino acids has been observed in a variety of contexts, less work has been done to directly assess the extent to which specific tRNAs are misacylated in vivo, and the identity of the misacylated amino acid moiety. Here we describe tRNA isoacceptor specific aminoacylation profiling (ISAP), a method to identify and quantify the amino acids attached to a tRNA species in vivo. ISAP allows compilation of aminoacylation profiles for specific isoacceptors tRNAs. To demonstrate the efficacy and …

Maintenance Of Transcription-Translation Coupling By Elongation Factor P, Sara Elgamal, Irina Artsimovitch, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Under conditions of tight coupling between translation and transcription, the ribosome enables synthesis of full-length mRNAs by preventing both formation of intrinsic terminator hairpins and loading of the transcription termination factor Rho. While previous studies have focused on transcription factors, we investigated the role of Escherichia coli elongation factor P (EF-P), an elongation factor required for efficient translation of mRNAs containing consecutive proline codons, in maintaining coupled translation and transcription. In the absence of EF-P, the presence of Rho utilization (rut) sites led to an ~30-fold decrease in translation of polyproline-encoding mRNAs. Coexpression of the Rho inhibitor Psu …

Relationship Between Bone-Specific Physical Activity Scores And Measures For Body Composition And Bone Mineral Density In Healthy Young College Women., Sojung Kim, Wi-Young So, Jooyoung Kim, Dong Jun Sung

Faculty Scholarship for the College of Science & Mathematics

OBJECTIVE: The purpose of this cross-sectional study was to investigate the relationship between bone-specific physical activity (BPAQ) scores, body composition, and bone mineral density (BMD) in healthy young college women.

METHODS: Seventy-three college women (21.7 ± 1.8 years; 162.1 ± 4.6 cm; 53.9 ± 5.8 kg) between the ages of 19 and 26 years were recruited from the universities in Seoul and Gyeonggi province, South Korea. We used dual energy X-ray absorptiometry to measure the lumbar spine (L2-L4) and proximal femur BMD (left side; total hip, femoral neck). The BPAQ scores (past, pBPAQ; current, cBPAQ; total, tBPAQ) were used to …

Maternal Sleep Loss During Fetal Development Alters Offspring Endocrine Responses To Stress Throughout Life, Audrey Brown

Mahurin Honors College Capstone Experience/Thesis Projects

The hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids, including corticosterone (CORT), in response to stress. CORT then negatively feeds back to inhibit its own production by binding to glucocorticoid receptors (GRs) in the hypothalamus and pituitary gland. The HPA axis is subject to “programming” by abnormal stimuli during early development, which may permanently alter how the HPA axis responds to stress. These altered responses have been linked to an increased risk for human psychiatric and metabolic disorders in later life, but the mechanism by which this happens is not fully understood. This study tests the hypothesis that changes to GR expression patterns …

Effects Of Echinostoma Trivolvis Metacercariae Infection During Development And Metamorphosis Of The Wood Frog (Lithobates Sylvaticus), Sarah A. Orlofske, Lisa K. Belden, William A. Hopkins

Biology Faculty Publications

Many organisms face energetic trade-offs between defense against parasites and other host processes that may determine overall consequences of infection. These trade-offs may be particularly evident during unfavorable environmental conditions or energetically demanding life history stages. Amphibian metamorphosis, an ecologically important developmental period, is associated with drastic morphological and physiological changes and substantial energetic costs. Effects of the trematode parasite Echinostoma trivolvis have been documented during early amphibian development, but effects during later development and metamorphosis are largely unknown. Using a laboratory experiment, we examined the energetic costs of late development and metamorphosis coupled with E. trivolvis infection in wood …

Predominant Expression Of Alzheimer’S Disease-Associated Bin1 In Mature Oligodendrocytes And Localization To White Matter Tracts, Pierre De Rossi, Virginie Buggia-Prévot, Benjamin L. L. Clayton, Jared B. Vasquez, Carson Van Sanford, Robert J. Andrew, Ruben Lesnick, Alexandra Botté, Carole Deyts, Someya Salem, Eshaan Rao, Richard C. Rice, Angèle Parent, Satyabrata Kar, Brian Popko, Peter Pytel, Steven Estus, Gopal Thinakaran

Physiology Faculty Publications

Background: Genome-wide association studies have identified BIN1 within the second most significant susceptibility locus in late-onset Alzheimer’s disease (AD). BIN1 undergoes complex alternative splicing to generate multiple isoforms with diverse functions in multiple cellular processes including endocytosis and membrane remodeling. An increase in BIN1 expression in AD and an interaction between BIN1 and Tau have been reported. However, disparate descriptions of BIN1 expression and localization in the brain previously reported in the literature and the lack of clarity on brain BIN1 isoforms present formidable challenges to our understanding of how genetic variants in BIN1 increase the risk for AD.

Methods: …

Effect Of Taste Stimuli On Swallowing Function In Persons With Traumatic Injuries, Megan Asselin, Angela M. Dietsch

UCARE Research Products

Background

Swallowing disorders are prevalent and costly. As of now, there are limited therapeutic options available to treat them. Extant research in limited populations has suggested that swallowing mechanics can be improved by extremely sour liquids, but this has not been tested in traumatically injured populations. However, sour tastants are unpleasant, and more palatable taste mixtures have not been tested.

Methods

The quantitative data were extracted from an existing pool of de-identified video fluoroscopic swallowing studies (moving radiographs) obtained from traumatically injured young adults under another research protocol. Each participant completed swallows of custom-mixed plain, sour, and sweet-sour boluses. Positions …

Cellular And Subcellular Oxidative Stress Parameters Following Severe Spinal Cord Injury, Nishant P. Visavadiya, Samir P. Patel, Jenna L. Vanrooyen, Patrick G. Sullivan, Alexander G. Rabchevsky

Spinal Cord and Brain Injury Research Center Faculty Publications

The present study undertook a comprehensive assessment of the acute biochemical oxidative stress parameters in both cellular and, notably, mitochondrial isolates following severe upper lumbar contusion spinal cord injury (SCI) in adult female Sprague Dawley rats. At 24 h post-injury, spinal cord tissue homogenate and mitochondrial fractions were isolated concurrently and assessed for glutathione (GSH) content and production of nitric oxide (NO^•), in addition to the presence of oxidative stress markers 3-nitrotyrosine (3-NT), protein carbonyl (PC), 4-hydroxynonenal (4-HNE) and lipid peroxidation (LPO). Moreover, we assessed production of superoxide (O₂^•-) and hydrogen peroxide (H₂O …

Altered Differential Control Of Sympathetic Outflow Following Sedentary Conditions: Role Of Subregional Neuroplasticity In The Rvlm, Madhan Subramanian, Patrick J. Mueller

Physiology Faculty Research Publications

Despite the classically held belief of an “all-or-none” activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA) can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA) but not lumbar SNA (LSNA) to activation of the rostral ventrolateral medulla (RVLM) in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would …

Repeated Closed Head Injury In Mice Results In Sustained Motor And Memory Deficits And Chronic Cellular Changes, Amanda Nicholle Bolton Hall, Binoy Joseph, Jennifer M. Brelsfoard, Kathryn E. Saatman

Spinal Cord and Brain Injury Research Center Faculty Publications

Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at …