Medical Neurobiology Commons^™

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …

Neural Correlates Of Fear Extinction: Investing The Impact Of Puberty And Sex In Children And Adolescents Through Neuroimaging, Sneha Bhargava, Clara Zundel, Samantha Ely, Carmen Carpenter, Reem Tamimi, Leah Gowatch, Mackenna Shampine, Emilie-Clare O'Mara, Jovan Jande, Shravya Chanamolu, Ahmad Almaat, Hilary Marusak

Medical Student Research Symposium

Fear-based disorders, including anxiety and posttraumatic stress disorder, are more prevalent in females than males. Steroid hormones (e.g., estradiol) are involved in fear extinction learning and later recall—a process implicated in the pathophysiology of fear-based disorders. Fear-based disorders commonly emerge during the transition from childhood to adolescence, a period marked by the onset of puberty and a natural increase of steroid hormones. Here, we examined the effects of puberty, sex, and their interaction on extinction recall and underlying neural circuitry in youth. Eighty-five youth (6-17 years, 46% female) completed a two-day Pavlovian fear extinction paradigm while undergoing functional magnetic resonance …

Enriched Environment Contributes To The Recovery From Neurotoxin-Induced Parkinson’S Disease Pathology, Daphne Alcala Zúñiga, Erika Espinoza-Torres, Ranjit Kumar Das, Magaly Vargas, Alejandro Lopez-Juarez, Masoud M. Zarei, Kelsey Baker, Mario Gil, Hansapani Rodrigo, Upal Roy

Health & Biomedical Sciences Faculty Publications and Presentations

Parkinson’s disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with …

Blood And Mri Biomarkers Of Mild Traumatic Brain Injury In Non-Concussed Collegiate Football Players, Eunhan Cho, Joshua Granger, Bailey Theall, Nathan Lemoine, Derek Calvert, Jack Marucci, Shelly Mullenix, Hollis O’Neal, Tomas Jacome, Brian A. Irving, Neil M. Johannsen, Owen Carmichael, Guillaume Spielmann

School of Medicine Faculty Publications

Football has one of the highest incidence rates of mild traumatic brain injury (mTBI) among contact sports; however, the effects of repeated sub-concussive head impacts on brain structure and function remain under-studied. We assessed the association between biomarkers of mTBI and structural and functional MRI scans over an entire season among non-concussed NCAA Division I linemen and non-linemen. Concentrations of S100B, GFAP, BDNF, NFL, and NSE were assessed in 48 collegiate football players (32 linemen; 16 non-linemen) before the start of pre-season training (pre-camp), at the end of pre-season training (pre-season), and at the end of the competitive season (post-season). …

Elovanoid-N34 Modulates Txnrd1 Key In Protection Against Oxidative Stress-Related Diseases, Jorgelina M. Calandria, Surjyadipta Bhattacharjee, Sayantani Kala-Bhattacharjee, Pranab K. Mukherjee, Yuehan Feng, Jakob Vowinckel, Tobias Treiber, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

The thioredoxin (TXN) system is an NADPH + H+/FAD redox-triggered effector that sustains homeostasis, bioenergetics, detoxifying drug networks, and cell survival in oxidative stress-related diseases. Elovanoid (ELV)-N34 is an endogenously formed lipid mediator in neural cells from omega-3 fatty acid precursors that modulate neuroinflammation and senescence gene programming when reduction-oxidation (redox) homeostasis is disrupted, enhancing cell survival. Limited proteolysis (LiP) screening of human retinal pigment epithelial (RPE) cells identified TXNRD1 isoforms 2, 3, or 5, the reductase of the TXN system, as an intracellular target of ELV-N34. TXNRD1 silencing confirmed that the ELV-N34 target was isoform 2 or 3. This …

Dha Shortage Causes The Early Degeneration Of Photoreceptors And Rpe In Mice With Peroxisomal Β-Oxidation Deficiency, Daniëlle Swinkels, Sai Kocherlakota, Yannick Das, Adriaan D. Dane, Eric J.M. Wever, Frédéric M. Vaz, Nicolas G. Bazan, Paul P. Van Veldhoven, Myriam Baes

School of Medicine Faculty Publications

PURPOSE. Patients deficient in peroxisomal β-oxidation, which is essential for the synthesis of docosahexaenoic acid (DHA, C22:6n-3) and breakdown of very-long-chain polyunsaturated fatty acids (VLC-PUFAs), both important components of photoreceptor outer segments, develop retinopathy present with retinopathy. The representative mouse model lacking the central enzyme of this pathway, multifunctional protein 2 (Mfp2−/−), also show early-onset retinal decay and cell-autonomous retinal pigment epithelium (RPE) degeneration, accompanied by reduced plasma and retinal DHA levels. In this study, we investigated whether DHA supplementation can rescue the retinal degeneration of Mfp2−/− mice. METHODS. Mfp2+/− breeding pairs and their offspring were fed a 0.12% DHA …

Ca2+-Regulated Expression Of High Affinity Methylaminoisobutryic Acid Transport In Hippocampal Neurons Inhibited By Riluzole And Novel Neuroprotective Aminothiazoles, Jeffrey D. Erickson, Thomas Kyllo, Heike Wulff

School of Medicine Faculty Publications

High affinity methylaminoisobutyric acid(MeAIB)/glutamine(Gln) transport activity regulated by neuronal firing occurs at the plasma membrane in mature rat hippocampal neuron-enriched cultures. Spontaneous Ca2+-regulated transport activity was similarly inhibited by riluzole, a benzothiazole anticonvulsant agent, and by novel naphthalenyl substituted aminothiazole derivatives such as SKA-378. Here, we report that spontaneous transport activity is stimulated by 4-aminopyridine (4-AP) and that phorbol-myristate acetate (PMA) increases high K+ stimulated transport activity that is inhibited by staurosporine. 4-AP-stimulated spontaneous and PMA-stimulated high K+-induced transport is not present at 7 days in vitro (DIV) and is maximal by DIV∼21. The relative affinity for MeAIB is similar …

Integrated Inflammatory Signaling Landscape Response After Delivering Elovanoid Free-Fatty-Acid Precursors Leading To Experimental Stroke Neuroprotection, Madigan M. Reid, Ludmila Belayev, Larissa Khoutorova, Pranab K. Mukherjee, Andre Obenaus, Kierany Shelvin, Stacey Knowles, Sung Ha Hong, Nicolas G. Bazan

School of Graduate Studies Faculty Publications

Despite efforts to identify modulatory neuroprotective mechanisms of damaging ischemic stroke cascade signaling, a void remains on an effective potential therapeutic. The present study defines neuroprotection by very long-chain polyunsaturated fatty acid (VLC-PUFA) Elovanoid (ELV) precursors C-32:6 and C-34:6 delivered intranasally following experimental ischemic stroke. We demonstrate that these precursors improved neurological deficit, decreased T2WI lesion volume, and increased SMI-71 positive blood vessels and NeuN positive neurons, indicating blood–brain barrier (BBB) protection and neurogenesis modulated by the free fatty acids (FFAs) C-32:6 and C-34:6. Gene expression revealed increased anti-inflammatory and pro-homeostatic genes and decreases in expression of pro-inflammatory genes in …

Rod-Specific Downregulation Of Omega-3 Very-Long-Chain Polyunsaturated Fatty Acid Pathway In Age-Related Macular Degeneration, William C. Gordon, Marie Audrey I. Kautzmann, Bokkyoo Jun, Megan L. Cothern, Zhide Fang, Nicolas G. Bazan

School of Medicine Faculty Publications

Docosahexaenoic acid (DHA; 22:6) plays a key role in vision and is the precursor for very-long-chain polyunsaturated fatty acids (VLC-PUFAs). The release of 32- and 34-carbon VLC-PUFAs and DHA from sn-1 and sn-2 of phosphatidylcholine (PC) leads to the synthesis of cell-survival mediators, the elovanoids (ELVs) and neuroprotectin D1 (NPD1), respectively. Macula and periphery from age-related macular degeneration (AMD) donor retinas were assessed for the availability of DHA-related lipids by LC-MS/MS-based lipidomic analysis and MALDI-molecular imaging. We found reduced retina DHA and VLC-PUFA pathways to synthesize omega-3 ELVs from precursors that likely resulted in altered disks and photoreceptor loss. Additionally, …

Cerebellar Interneurons Control Fear Memory Consolidation Via Learning-Induced Hcn Plasticity, Kathryn Lynn Carzoli, Georgios Kogias, Jessica Fawcett-Patel, Si-Qiong J. Liu

School of Medicine Faculty Publications

While synaptic plasticity is considered the basis of learning and memory, modifications of the intrinsic excitability of neurons can amplify the output of neuronal circuits and consequently change behavior. However, the mechanisms that underlie learning-induced changes in intrinsic excitability during memory formation are poorly understood. In the cerebellum, we find that silencing molecular layer interneurons completely abolishes fear memory, revealing their critical role in memory consolidation. The fear conditioning paradigm produces a lasting reduction in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in these interneurons. This change increases intrinsic membrane excitability and enhances the response to synaptic stimuli. HCN loss is driven …

Lipoxin A4 (Lxa4) Reduces Alkali-Induced Corneal Inflammation And Neovascularization And Upregulates A Repair Transcriptome, Jiucheng He, Thang L. Pham, Azucena H. Kakazu, Abhilash Ponnath, Khanh V. Do, Haydee E.P. Bazan

School of Graduate Studies Faculty Publications

Purpose: To investigate the anti-inflammatory and anti-angiogenic effects of the bioactive lipid mediator LXA4 on a rat model of severe corneal alkali injury. Methods: To induce a corneal alkali injury in the right eyes of anesthetized Sprague Dawley rats. They were injured with a Φ 4 mm filter paper disc soaked in 1 N NaOH placed on the center of the cornea. After injury, the rats were treated topically with LXA4 (65 ng/20 μL) or vehicle three times a day for 14 days. Corneal opacity, neovascularization (NV), and hyphema were recorded and evaluated in a blind manner. Pro-inflammatory cytokine expression …

Dynamic Role Of Exosome Micrornas In Cancer Cell Signaling And Their Emerging Role As Noninvasive Biomarkers, Jaya Aseervatham

Department of Neurology Faculty Papers

Exosomes are extracellular vesicles that originate from endosomes and are released by all cells irrespective of their origin or type. They play an important role in cell communication and can act in an autocrine, endocrine, or paracrine fashion. They are 40–150 nm in diameter and have a similar composition to the cell of origin. An exosome released by a particular cell is unique since it carries information about the state of the cell in pathological conditions such as cancer. miRNAs carried by cancer-derived exosomes play a multifaceted role by taking part in cell proliferation, invasion, metastasis, epithelial–mesenchymal transition, angiogenesis, apoptosis, …

A Conditional Strategy For Cell-Type-Specific Labeling Of Endogenous Excitatory Synapses In Drosophila, Michael J. Parisi, Michael A. Aimino, Timothy J. Mosca

Farber Institute for Neuroscience Faculty Papers

Chemical neurotransmission occurs at specialized contacts where neurotransmitter release machinery apposes neurotransmitter receptors to underlie circuit function. A series of complex events underlies preand postsynaptic protein recruitment to neuronal connections. To better study synaptic development in individual neurons, we need cell-type-specific strategies to visualize endogenous synaptic proteins. Although presynaptic strategies exist, postsynaptic proteins remain less studied because of a paucity of cell-type-specific reagents. To study excitatory postsynapses with cell-type specificity, we engineered dlg1[4K], a conditionally labeled marker of Drosophila excitatory postsynaptic densities. With binary expression systems, dlg1[4K] labels central and peripheral postsynapses in larvae and adults. Using dlg1[4K], we find …

Refinement Of Saliva Microrna Biomarkers For Sports-Related Concussion, Steven D. Hicks, Cayce Onks, Raymond Y. Kim, Kevin J. Kim, Kevin J. Zhen, Jayson Loeffert, Andrea C. Loeffert, Robert P. Olympia, Gregory Fedorchak, Samantha Devita, Zofia Gagnon, Callan Mcloughlin, Miguel M. Madeira, Scott L. Zuckerman, Timothy Lee, Matthew Heller, Chuck Monteith, Thomas R. Campbell, Christopher Neville, Elise Fengler, Michael N. Dretsch

Rehabilitation Sciences Faculty Publications

Purpose

Recognizing sport-related concussion (SRC) is challenging and relies heavily on subjective symptom reports. An objective, biological marker could improve recognition and understanding of SRC. There is emerging evidence that salivary micro-ribonucleic acids (miRNAs) may serve as biomarkers of concussion; however, it remains unclear whether concussion-related miRNAs are impacted by exercise. We sought to determine whether 40 miRNAs previously implicated in concussion pathophysiology were affected by participation in a variety of contact and non-contact sports. Our goal was to refine a miRNA-based tool capable of identifying athletes with SRC without the confounding effects of exercise.

Methods

This case-control study harmonized …

The Effects Of Exosomal Derived Tsg-6 On Microglia Activation, Jonathan A. Martinez, Rajashekhar Gangaraju Md

Longitudinal Scholar's Project

Following a traumatic brain injury, microglia become overactive for long periods and display pathologic behavior. We have shown that concentrated conditioned media from adipose tissue-derived mesenchymal stem cells (MSC-CCM) can suppress microglial activation. In this pilot study, we evaluated the efficacy of exosomes containing TNF-stimulated gene 6 (TSG6) derived from MSC-CCM on decreasing microglial activation in vitro via phagocytic activity and pro-inflammatory microglial gene expression.

Regeneration Of Neurons In Human Brain Tissue; A Revolutionary Concept With Therapeutic Potential, Mackenzie R. Dunn

Other Undergraduate Research

There is current research to suggest that endogenous neuronal regeneration, exogenous neuronal stem cell transplantation and glial cell reprogramming could be prospective therapeutic treatments for neurodegeneration and traumatic injury. With these conditions, there is significant brain atrophy, loss of neurons and loss of synaptic connections which can have devastating effects on executive functioning, cognition, learning and memory. This review will examine these modern approaches to adult neurogenesis, and assess the viable mechanisms and future outlook of these three therapies for neurological regenerative medicine.

Group-Based Four-Dimensional Brain Mapping Of Executive Control, Matthew T. Brennan, Kazuki Sakakura Md, Masaki Sonoda Md, Phd, Aimee Luat Md, Neena Marupudi, Sandeep Sood Md, Eishi Asano Md, Phd

Medical Student Research Symposium

Rationale: Humans utilize executive control processes to carry out non-automatic tasks. These tasks require coordination from higher brain centers to both suppress inappropriate behaviors and initiate correct responses. The goal of this study is to generate a novel, dynamic brain atlas to visualize and understand the network dynamics underlying executive control.

Methods: We studied 547 non-epileptic intracranial electrode sites sampled from seven patients with focal epilepsy. Each patient performed two types of verbal tasks: word-reading and Stroop color-naming. Mixed model analysis compared high-gamma cortical activation prior to response onset between the word-reading and Stroop color-naming tasks. Based on mixed model …

Intravital Imaging Of Cellular Response Due To Traumatic Brain Injury Using Confocal Microscopy, Enoch G. Kim, Jeffrey Horbatiuk, Carolyn Harris

Medical Student Research Symposium

Introduction: Cellular reaction to traumatic brain injury is complex and involves considerable interactions between cells and reactivity to foreign bodies. Our objective was to assess neurons, microglia, astrocytes, and intracellular Ca²⁺ signaling by creating a novel confocal microscopy technique involving an air immersed lens that does not sacrifice resolution and limits signal attenuation. This study aimed to create a consistent dynamic methodology to observe the cortical cellular response using real-time intravital imaging as trauma is being induced.

Methods: Once surgical plane was achieved, rodent cortices were exposed via craniotomy and blunt insertion with a silicone shunt catheter into the …

Varied Performance Of Picture Description Task As A Screening Tool Across Mci Subtypes, Joan A. Mefford, Zilong Zhao, Leah Heilier, Man Xu, Guifeng Zhou, Rachel Mace, Kelly L. Sloane, Shannon M. Sheppard, Shenly Glenn

Communication Sciences and Disorders Faculty Articles and Research

A picture description task is a component of Miro Health’s platform for self-administration of neurobehavioral assessments. Picture description has been used as a screening tool for identification of individuals with Alzheimer’s disease and mild cognitive impairment (MCI), but currently requires in-person administration and scoring by someone with access to and familiarity with a scoring rubric. The Miro Health implementation allows broader use of this assessment through self-administration and automated processing, analysis, and scoring to deliver clinically useful quantifications of the users’ speech production, vocal characteristics, and language. Picture description responses were collected from 62 healthy controls (HC), and 33 participants …

Massive Loss Of Proprioceptive Ia Synapses In Rat Spinal Motoneurons After Nerve Crush Injuries In The Postnatal Period, Ariadna Arbat-Plana, Sara Bolívar, Xavier Navarro, Esther Udina, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries (PNIs) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from α-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed, and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. The goal of this study was to analyze …

Loss-Of-Function KCa2.2 Mutations Abolish Channel Activity, Young-Woo Nam, Mohammad Asikur Rahman, Grace Yang, Razan Orfali, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium channels subtype 2 (K_Ca2.2, also called SK2) are operated exclusively by a Ca²⁺-calmodulin gating mechanism. Heterozygous genetic mutations of K_Ca2.2 channels have been associated with autosomal dominant neurodevelopmental disorders including cerebellar ataxia and tremor in humans and rodents. Taking advantage of these pathogenic mutations, we performed structure-function studies of the rat K_Ca2.2 channel. No measurable current was detected from HEK293 cells heterologously expressing these pathogenic K_Ca2.2 mutants. When co-expressed with the K_Ca2.2_WT channel, mutations of the pore-lining amino acid residues (I360M, Y362C, G363S …

Fast Blue And Cholera Toxin-B Survival Guide For Alpha-Motoneurons Labeling: Less Is Better In Young B6sjl Mice, But More Is Better In Aged C57bl/J Mice, Hasan Farid, Weston B. Gleford, Lori L. Goss, Teresa L. Garrett, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Fast Blue (FB) and Cholera Toxin-B (CTB) are two retrograde tracers extensively used to label alpha-motoneurons (α-MNs). The overall goals of the present study were to (1) assess the effectiveness of different FB and CTB protocols in labeling α-MNs, (2) compare the labeling quality of these tracers at standard concentrations reported in the literature (FB 2% and CTB 0.1%) versus lower concentrations to overcome tracer leakage, and (3) determine an optimal protocol for labeling α-MNs in young B6SJL and aged C57Bl/J mice (when axonal transport is disrupted by aging). Hindlimb muscles of young B6SJL and aged C57Bl/J mice were intramuscularly …

G Protein-Coupled Receptor Kinase-2 (Grk-2) Controls Exploration Through Neuropeptide Signaling In Caenorhabditis Elegans, Kristen Davis, Christo Mitchell, Olivia Weissenfels, Jihong Bai, David M. Raizen, Michael Ailion, Irini Topalidou

Department of Neuroscience Faculty Papers

Animals alter their behavior in manners that depend on environmental conditions as well as their developmental and metabolic states. For example, C. elegans is quiescent during larval molts or during conditions of satiety. By contrast, worms enter an exploration state when removed from food. Sensory perception influences movement quiescence (defined as a lack of body movement), as well as the expression of additional locomotor states in C. elegans that are associated with increased or reduced locomotion activity, such as roaming (exploration behavior) and dwelling (local search). Here we find that movement quiescence is enhanced, and exploration behavior is reduced in …

Infiltrating Cd8+ T Cells Exacerbate Alzheimer’S Disease Pathology In A 3d Human Neuroimmune Axis Model, Jefin Jose, Devam Purohit

VCU's Medical Journal Club: The Work of Future Health Professionals

In this study, Jorfi et al. employed a neuroimmune axis model containing neurons, astrocytes, and microglia to examine the role of immune cells in Alzheimer's disease. Jorfi et al. found that T cells selectively infiltrated the BRAIN compartment of the neuroimmune axis model as compared to B cells and monocytes. Jorfi et al. further found that CD8+ T cells demonstrated heightened cytotoxicity in the Alzheimer's disease brain, illuminating the role of immune cells in neurodegeneration. Upon further examination, the CXCR3-CXCL10 signaling pathway was found to have an important role in inflammation.

Nasal Accumulation And Metabolism Of Δ9-Tetrahydrocannabinol Following Aerosol (‘Vaping’) Administration In An Adolescent Rat Model, Alexa Torrens, Christina M Ruiz, Maricela X Martinez, Alex Mabou Tagne, Pritam Roy, Dakota Grimes, Faizy Ahmed, Valeria Lallai, Victoria Inshishian, Malia Bautista, Yen-Chu Chen, Marilyn A. Huestis, Aditi Das, Christie D Fowler, Stephen V Mahler, Daniele Piomelli

Institute of Emerging Health Professions Faculty Papers

Passive aerosol exposure to Δ9-tetrahydrocannabinol (THC) in laboratory animals results in faster onset of action and less extensive liver metabolism compared to most other administration routes and might thus provide an ecologically relevant model of human cannabis inhalation. Previous studies have, however, overlooked the possibility that rodents, as obligate nose breathers, may accumulate aerosolized THC in the nasal cavity, from where the drug might directly diffuse to the brain. To test this, we administered THC (ten 5-s puffs of 100 mg/mL of THC) to adolescent (31-day-old) Sprague-Dawley rats of both sexes. We used liquid chromatography/tandem mass spectrometry to quantify the …

A Genome-Wide In Vivo Crispr Screen Identifies Essential Regulators Of T Cell Migration To The Cns In A Multiple Sclerosis Model, Jefin Jose

VCU's Medical Journal Club: The Work of Future Health Professionals

Kendirli et al. (2023) used a CRISPR screen to determine the proteins involved in T cell migration into the CNS in multiple sclerosis. Overall, eighteen facilitators and five brakes to T cell infiltration into the CNS were identified. Kendirli et al. specifically identified ITGA4, FERMT3, and HSP90B1 to make up the adhesion module, CXCR3, GNAI2, and TBX21 to make up the chemotaxis module, and GRK2 and S1PR2 to make up the egress module. This study demonstrated the ability of a CRISPR screen to identify elements in a disease process and thus identify targets for future multiple sclerosis therapies.

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iii: Executive Functions, Eliyas Jeffay, Jennie Ponsford, Amber Harnett, Shannon Janzen, Eleni Patsakos, Jacinta Douglas, Mary Kennedy, Ailene Kua, Robert Teasell, Penny Welch-West, Mark Theodore Bayley, Robin Green

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments.

Methods:

An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice.

Results:

A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 …

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury: What’S Changed From 2014 To Now?, Mark Theodore Bayley, Shannon Janzen, Amber Harnett, Peter Bragge, Leanne Togher, Ailene Kua, Eleni Patsakos, Lyn S. Turkstra, Robert Teasell, Mary Kennedy, Shawn Marshall, Jennie Ponsford

Communication Sciences and Disorders Faculty Articles and Research

IT IS CRITICAL TO KEEP clinical practice guidelines (CPGs) up to date through integration of the latest evidence. Therefore, it is with great excitement that the INCOG team presents the INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury (TBI). In this brief introduction, we provide an overview of changes in the evidence from 2014; share insights into the current state and challenges implementing cognitive rehabilitation; and provide an overview of INCOG 2022.

Incog 2.0 Guidelines For Cognitive Rehabilitation Following Traumatic Brain Injury, Part Iv: Cognitive-Communication And Social Cognition Disorders, Leanne Togher, Jacinta Douglas, Lyn S. Turkstra, Penny Welch-West, Shannon Janzen, Amber Harnett, Mary Kennedy, Ailene Kua, Eleni Patsakos, Jennie Ponsford, Robert Teasell, Mark Theodore Bayley, Catherine Wiseman-Hakes

Communication Sciences and Disorders Faculty Articles and Research

Introduction:

Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others' emotions, and infer others' thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person's ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition.

Methods:

An expert panel of clinicians/researchers reviewed evidence published since …