scholarly journals RhoA-ROCK Signaling as a Therapeutic Target in Traumatic Brain Injury

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 245 ◽  
Author(s):  
Shalaka Mulherkar ◽  
Kimberley F. Tolias
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Traumatic Event ◽  
Treatment Options ◽  
Work Productivity ◽  
Rho Kinase ◽  
Small Gtpase ◽  
Cns Injury ◽  
Functional Impairments ◽  
The Brain

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. TBIs, which range in severity from mild to severe, occur when a traumatic event, such as a fall, a traffic accident, or a blow, causes the brain to move rapidly within the skull, resulting in damage. Long-term consequences of TBI can include motor and cognitive deficits and emotional disturbances that result in a reduced quality of life and work productivity. Recovery from TBI can be challenging due to a lack of effective treatment options for repairing TBI-induced neural damage and alleviating functional impairments. Central nervous system (CNS) injury and disease are known to induce the activation of the small GTPase RhoA and its downstream effector Rho kinase (ROCK). Activation of this signaling pathway promotes cell death and the retraction and loss of neural processes and synapses, which mediate information flow and storage in the brain. Thus, inhibiting RhoA-ROCK signaling has emerged as a promising approach for treating CNS disorders. In this review, we discuss targeting the RhoA-ROCK pathway as a therapeutic strategy for treating TBI and summarize the recent advances in the development of RhoA-ROCK inhibitors.

scholarly journals A Role for Nanoparticles in Treating Traumatic Brain Injury

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 473 ◽  
Author(s):  
Badrul Alam Bony ◽  
Forrest M. Kievit
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Treatment Options ◽  
Unmet Need ◽  
Economic Loss ◽  
Phase Iii ◽  
Target Engagement ◽  
Post Injury ◽  
The Brain

Traumatic brain injury (TBI) is one of the main causes of disability in children and young adults, as well as a significant concern for elderly individuals. Depending on the severity, TBI can have a long-term impact on the quality of life for survivors of all ages. The primary brain injury can result in severe disability or fatality, and secondary brain damage can increase the complexities in cellular, inflammatory, neurochemical, and metabolic changes in the brain, which can last decades post-injury. Thus, survival from a TBI is often accompanied by lifelong disabilities. Despite the significant morbidity, mortality, and economic loss, there are still no effective treatment options demonstrating an improved outcome in a large multi-center Phase III trial, which can be partially attributed to poor target engagement of delivered therapeutics. Thus, there is a significant unmet need to develop more effective delivery strategies to overcome the biological barriers that would otherwise inhibit transport of materials into the brain to prevent the secondary long-term damage associated with TBI. The complex pathology of TBI involving the blood-brain barrier (BBB) has limited the development of effective therapeutics and diagnostics. Therefore, it is of great importance to develop novel strategies to target the BBB. The leaky BBB caused by a TBI may provide opportunities for therapeutic delivery via nanoparticles (NP). The focus of this review is to provide a survey of NP-based strategies employed in preclinical models of TBI and to provide insights for improved NP based diagnostic or treatment approaches. Both passive and active delivery of various NPs for TBI are discussed. Finally, potential therapeutic targets where improved NP-mediated delivery could increase target engagement are identified with the overall goal of providing insight into open opportunities for NP researchers to begin research in TBI.

scholarly journals Hericium erinaceus and Coriolus versicolor Modulate Molecular and Biochemical Changes after Traumatic Brain Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 898
Author(s):  
Ramona D’Amico ◽  
Angela Trovato Salinaro ◽  
Roberta Fusco ◽  
Marika Cordaro ◽  
Daniela Impellizzeri ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Oral Treatment ◽  
Coriolus Versicolor ◽  
Strong Increase ◽  
Functional Impairments ◽  
Physical Force ◽  
Hericium Erinaceus ◽  
The Impact ◽  
The Brain

Traumatic brain injury (TBI) is a major health and socioeconomic problem affecting the world. This condition results from the application of external physical force to the brain which leads to transient or permanent structural and functional impairments. TBI has been shown to be a risk factor for neurodegeneration which can lead to Parkinson’s disease (PD) for example. In this study, we wanted to explore the development of PD-related pathology in the context of an experimental model of TBI and the potential ability of Coriolus versicolor and Hericium erinaceus to prevent neurodegenerative processes. Traumatic brain injury was induced in mice by controlled cortical impact. Behavioral tests were performed at various times: the animals were sacrificed 30 days after the impact and the brain was processed for Western blot and immunohistochemical analyzes. After the head injury, a significant decrease in the expression of tyrosine hydroxylase and the dopamine transporter in the substantia nigra was observed, as well as significant behavioral alterations that were instead restored following daily oral treatment with Hericium erinaceus and Coriolus versicolor. Furthermore, a strong increase in neuroinflammation and oxidative stress emerged in the vehicle groups. Treatment with Hericium erinaceus and Coriolus versicolor was able to prevent both the neuroinflammatory and oxidative processes typical of PD. This study suggests that PD-related molecular events may be triggered on TBI and that nutritional fungi such as Hericium erinaceus and Coriolus versicolor may be important in redox stress response mechanisms and neuroprotection, preventing the progression of neurodegenerative diseases such as PD.

scholarly journals Coagulopathy induced by traumatic brain injury: systemic manifestation of a localized injury

Blood ◽  
2018 ◽  
Vol 131 (18) ◽  
pp. 2001-2006 ◽  
Author(s):  
Jianning Zhang ◽  
Fangyi Zhang ◽  
Jing-fei Dong
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Clinical Outcomes ◽  
Intracranial Hemorrhage ◽  
Recent Progress ◽  
Treatment Options ◽  
Knowledge Gaps ◽  
Systemic Manifestation ◽  
The Brain

Abstract Traumatic brain injury (TBI)–induced coagulopathy is a common and well-recognized risk for poor clinical outcomes, but its pathogenesis remains poorly understood, and treatment options are limited and ineffective. We discuss the recent progress and knowledge gaps in understanding this lethal complication of TBI. We focus on (1) the disruption of the brain-blood barrier to disseminate brain injury systemically by releasing brain-derived molecules into the circulation and (2) TBI-induced hypercoagulable and hyperfibrinolytic states that result in persistent and delayed intracranial hemorrhage and systemic bleeding.

Head trauma: treatment and diagnostic aids

2020 ◽  
Vol 25 (11) ◽  
pp. 283-288
Author(s):  
Mark Lowrie
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Best Practice ◽  
Treatment Options ◽  
Brain Parenchyma ◽  
Primary Lesion ◽  
Trauma Treatment ◽  
Secondary Injury ◽  
Irreversible Damage ◽  
The Brain

Traumatic brain injury occurs frequently in dogs and cats. The primary lesion occurs at the time of injury and causes direct, irreversible damage to the brain parenchyma and vasculature. Secondary lesions occur in the minutes following the trauma as a result of a combination of physical and biochemical changes that lead to intracranial hypertension. It is this secondary injury that veterinarians are able to reduce. This article outlines the treatment options for patients with traumatic brain injury. There remains controversy over what constitutes best practice. This article addresses the main points regarding the clinical therapeutic options currently available.

Lessons Learned From Coaching Postsecondary Students With Traumatic Brain Injury

2020 ◽  
Vol 5 (1) ◽  
pp. 88-96
Author(s):  
Mary R. T. Kennedy
Keyword(s):  
College Students ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Sense Of Self ◽  
Scientific Evidence ◽  
Sudden Onset ◽  
Lessons Learned ◽  
Speech Language Pathologists ◽  
The Brain ◽  
Exhaustive List

Purpose The purpose of this clinical focus article is to provide speech-language pathologists with a brief update of the evidence that provides possible explanations for our experiences while coaching college students with traumatic brain injury (TBI). Method The narrative text provides readers with lessons we learned as speech-language pathologists functioning as cognitive coaches to college students with TBI. This is not meant to be an exhaustive list, but rather to consider the recent scientific evidence that will help our understanding of how best to coach these college students. Conclusion Four lessons are described. Lesson 1 focuses on the value of self-reported responses to surveys, questionnaires, and interviews. Lesson 2 addresses the use of immediate/proximal goals as leverage for students to update their sense of self and how their abilities and disabilities may alter their more distal goals. Lesson 3 reminds us that teamwork is necessary to address the complex issues facing these students, which include their developmental stage, the sudden onset of trauma to the brain, and having to navigate going to college with a TBI. Lesson 4 focuses on the need for college students with TBI to learn how to self-advocate with instructors, family, and peers.

Providing Care of Mild Traumatic Brain Injury by the Family Practice/Primary Care Optometrist

2018 ◽  
pp. 110-119
Keyword(s):  
Primary Care ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mild Traumatic Brain Injury ◽  
Family Practice ◽  
Advanced Training ◽  
Entry Level ◽  
The Family ◽  
Basic Understanding ◽  
The Brain

Primary Objectives: By extending the scope of knowledge of the primary care optometrist, the brain injury population will have expanded access to entry level neurooptometric care by optometric providers who have a basic understanding of their neurovisual problems, be able to provide some treatment and know when to refer to their colleagues who have advanced training in neuro-optometric rehabilitation.

scholarly journals Ulinastatin alleviates traumatic brain injury by reducing endothelin-1

2020 ◽  
Vol 12 (1) ◽  
pp. 001-008
Author(s):  
Ting Liu ◽  
Xing-Zhi Liao ◽  
Mai-Tao Zhou
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Western Blot ◽  
Water Content ◽  
Brain Edema ◽  
Rat Model ◽  
Neurosurgical Procedures ◽  
Brain Water Content ◽  
The Brain ◽  
Brain Water

Abstract Background Brain edema is one of the major causes of fatality and disability associated with injury and neurosurgical procedures. The goal of this study was to evaluate the effect of ulinastatin (UTI), a protease inhibitor, on astrocytes in a rat model of traumatic brain injury (TBI). Methodology A rat model of TBI was established. Animals were randomly divided into 2 groups – one group was treated with normal saline and the second group was treated with UTI (50,000 U/kg). The brain water content and permeability of the blood–brain barrier were assessed in the two groups along with a sham group (no TBI). Expression of the glial fibrillary acidic protein, endthelin-1 (ET-1), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry and western blot. Effect of UTI on ERK and PI3K/AKT signaling pathways was measured by western blot. Results UTI significantly decreased the brain water content and extravasation of the Evans blue dye. This attenuation was associated with decreased activation of the astrocytes and ET-1. UTI treatment decreased ERK and Akt activation and inhibited the expression of pro-inflammatory VEGF and MMP-9. Conclusion UTI can alleviate brain edema resulting from TBI by inhibiting astrocyte activation and ET-1 production.

scholarly journals Engineered glycomaterial implants orchestrate large-scale functional repair of brain tissue chronically after severe traumatic brain injury

2021 ◽  
Vol 7 (10) ◽  
pp. eabe0207
Author(s):  
Charles-Francois V. Latchoumane ◽  
Martha I. Betancur ◽  
Gregory A. Simchick ◽  
Min Kyoung Sun ◽  
Rameen Forghani ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Large Scale ◽  
Growth Factor Signaling ◽  
Neuronal Circuit ◽  
Reach To Grasp ◽  
Function Recovery ◽  
Cellular Repair ◽  
The Brain

Severe traumatic brain injury (sTBI) survivors experience permanent functional disabilities due to significant volume loss and the brain’s poor capacity to regenerate. Chondroitin sulfate glycosaminoglycans (CS-GAGs) are key regulators of growth factor signaling and neural stem cell homeostasis in the brain. However, the efficacy of engineered CS (eCS) matrices in mediating structural and functional recovery chronically after sTBI has not been investigated. We report that neurotrophic factor functionalized acellular eCS matrices implanted into the rat M1 region acutely after sTBI significantly enhanced cellular repair and gross motor function recovery when compared to controls 20 weeks after sTBI. Animals subjected to M2 region injuries followed by eCS matrix implantations demonstrated the significant recovery of “reach-to-grasp” function. This was attributed to enhanced volumetric vascularization, activity-regulated cytoskeleton (Arc) protein expression, and perilesional sensorimotor connectivity. These findings indicate that eCS matrices implanted acutely after sTBI can support complex cellular, vascular, and neuronal circuit repair chronically after sTBI.

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