Preclinical investigation of pegylated arginase 1 as a treatment for retina and brain injury

2021 ◽  
pp. 113923
Author(s):  
AbdelrahmanY. Fouda ◽  
Wael Eldahshan ◽  
Zhimin Xu ◽  
Tahira Lemtalsi ◽  
Esraa Shosha ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Liang ◽  
Nan Kang ◽  
Pinpin Li ◽  
Xuehua Liu ◽  
Ge Li ◽  
...  

Background: The neurological defect caused by secondary damage following traumatic brain injury (TBI) is considered critical for the management of TBI. Microglia (MG) are a resident brain macrophage that could differentiate into M1 type or M2 type in response to injury and repair. It is known that the MG transition from M1 phenotype to anti-inflammatory M2 phenotype might reduce secondary injury of TBI. So, a TBI animal model was established and we compared biomarkers of M1 and M2MG between the controls and experimental animals receiving hyperbaric oxygen therapy (HBOT). This study aimed to explore whether HBOT was an effective method to improve neural functional recovery via promoting the polarization of MG into M2 after TBI.Methods: The rats were randomly divided into four groups: SH (Sham-operated), SH + HBO (hyperbaric oxygen), TBI, and TBI + HBO. Each group included 42 rats, and each of these were divided into the following groups: 1, 6, 12, 24, 72 h, 7, and 14 days. The expression of M1 biomarker inducible nitric oxide synthase (iNOS), M2 biomarker arginase 1 (Arg1), associated cytokine tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) was evaluated after the observation time.Results: TBI significantly increased the expression levels of M1 marker iNOS and M2 markers Arg1 at different time points. The increased expression of iNOS was suppressed, while the expression level of Arg1 was enhanced by HBOT. Moreover, HBOT suppressed the pro-inflammatory TNF-α secreted by M1, and promoting the anti-inflammatory TGF-1β.Conclusions: In the present study, HBOT showed the effects on shift of M1 toward M2 phenotype with increased expression of M2 biomarkers and decreased expression of M1 biomarkers in the early stage after TBI.


2021 ◽  
pp. 0271678X2110286
Author(s):  
Hongjian Pu ◽  
Cheng Ma ◽  
Yongfang Zhao ◽  
Yangfan Wang ◽  
Wenting Zhang ◽  
...  

Traumatic brain injury (TBI) is commonly followed by long-term cognitive deficits that severely impact the quality of life in survivors. Recent studies suggest that microglial/macrophage (Mi/MΦ) polarization could have multidimensional impacts on post-TBI neurological outcomes. Here, we report that repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles for 4 weeks after controlled cortical impact improved hippocampus-dependent spatial and non-spatial cognitive functions in adult C57BL6 mice, as assessed by a battery of neurobehavioral tests for up to 5 weeks after TBI. IL-4-elicited enhancement of cognitive functions was associated with improvements in the integrity of the hippocampus at the functional ( e.g., long-term potentiation) and structural levels (CA3 neuronal loss, diffusion tensor imaging of white matter tracts, etc.). Mechanistically, IL-4 increased the expression of PPARγ and arginase-1 within Mi/MΦ, thereby driving microglia toward a global inflammation-resolving phenotype. Notably, IL-4 failed to shift microglial phenotype after TBI in Mi/MΦ-specific PPARγ knockout (mKO) mice, indicating an obligatory role for PPARγ in IL-4-induced Mi/MΦ polarization. Accordingly, post-TBI treatment with IL-4 failed to improve hippocampal integrity or cognitive functions in PPARγ mKO mice. These results demonstrate that administration of exogenous IL-4 nanoparticles stimulates PPARγ-dependent beneficial Mi/MΦ responses, and improves hippocampal function after TBI.


2019 ◽  
Vol 42 ◽  
Author(s):  
Colleen M. Kelley ◽  
Larry L. Jacoby

Abstract Cognitive control constrains retrieval processing and so restricts what comes to mind as input to the attribution system. We review evidence that older adults, patients with Alzheimer's disease, and people with traumatic brain injury exert less cognitive control during retrieval, and so are susceptible to memory misattributions in the form of dramatic levels of false remembering.


2019 ◽  
Vol 3 (6) ◽  
pp. 707-711 ◽  
Author(s):  
Andrew Peterson ◽  
Adrian M. Owen

In recent years, rapid technological developments in the field of neuroimaging have provided several new methods for revealing thoughts, actions and intentions based solely on the pattern of activity that is observed in the brain. In specialized centres, these methods are now being employed routinely to assess residual cognition, detect consciousness and even communicate with some behaviorally non-responsive patients who clinically appear to be comatose or in a vegetative state. In this article, we consider some of the ethical issues raised by these developments and the profound implications they have for clinical care, diagnosis, prognosis and medical-legal decision-making after severe brain injury.


2020 ◽  
Vol 5 (1) ◽  
pp. 88-96
Author(s):  
Mary R. T. Kennedy

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.


2019 ◽  
Vol 4 (6) ◽  
pp. 1267-1282
Author(s):  
Jessica Salley ◽  
Sarah Krusen ◽  
Margaret Lockovich ◽  
Bethany Wilson ◽  
Brenda Eagan-Johnson ◽  
...  

Purpose Through a hypothetical case study, this article aimed to describe an evidence-based approach for speech-language pathologists in managing students with moderate-to-severe traumatic brain injury (TBI), particularly within a formal statewide-supported school-based brain injury team model, such as the BrainSTEPS Brain Injury School Consulting Program operating in Pennsylvania and Colorado. Conclusion Upon transitioning from the medical setting back to school, children with TBI present with unique educational needs. Children with moderate-to-severe TBIs can demonstrate a range of strengths and deficits in speech, language, cognition, and feeding and swallowing, impacting their participation in various school activities. The specialized education, training, and insight of speech-language pathologists, in collaboration with multidisciplinary medical and educational team members, can enable the success of students with TBI when transitioning back to school postinjury ( DePompei & Blosser, 2019 ; DePompei & Tyler, 2018 ). This transition should focus on educational planning, implementation of strategies and supports, and postsecondary planning for vocations or higher education.


2019 ◽  
Vol 28 (3) ◽  
pp. 1363-1370 ◽  
Author(s):  
Jessica Brown ◽  
Katy O'Brien ◽  
Kelly Knollman-Porter ◽  
Tracey Wallace

Purpose The Centers for Disease Control and Prevention (CDC) recently released guidelines for rehabilitation professionals regarding the care of children with mild traumatic brain injury (mTBI). Given that mTBI impacts millions of children each year and can be particularly detrimental to children in middle and high school age groups, access to universal recommendations for management of postinjury symptoms is ideal. Method This viewpoint article examines the CDC guidelines and applies these recommendations directly to speech-language pathology practices. In particular, education, assessment, treatment, team management, and ongoing monitoring are discussed. In addition, suggested timelines regarding implementation of services by speech-language pathologists (SLPs) are provided. Specific focus is placed on adolescents (i.e., middle and high school–age children). Results SLPs are critical members of the rehabilitation team working with children with mTBI and should be involved in education, symptom monitoring, and assessment early in the recovery process. SLPs can also provide unique insight into the cognitive and linguistic challenges of these students and can serve to bridge the gap among rehabilitation and school-based professionals, the adolescent with brain injury, and their parents. Conclusion The guidelines provided by the CDC, along with evidence from the field of speech pathology, can guide SLPs to advocate for involvement in the care of adolescents with mTBI. More research is needed to enhance the evidence base for direct assessment and treatment with this population; however, SLPs can use their extensive knowledge and experience working with individuals with traumatic brain injury as a starting point for post-mTBI care.


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