Vol 6-1 Original Research Article

Polyethylene Glycol Treatment for Peripheral Nerve Repair in Preclinical Models

Davis B. Rippee1, Gabriella E. Glassman2, Sara C. Chaker3, Patrick E. Assi4, Jennifer Black, Alonda C. Pollins4, Jun Yao4, Wesley P. Thayer4,6*

1University of Mississippi School of Medicine, Jackson, MS, USA

2Florida State University College of Medicine, Tallahassee, FL, USA

3Vanderbilt University, Nashville, TN, USA

4Department of Plastic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

5Meharry Medical College, Nashville, TN, USA

6*Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

Introduction: Peripheral nerve injuries commonly result from trauma and can lead to devastating loss of sensory and motor function. A novel strategy to improve peripheral nerve regeneration is a chemical fusogen known as polyethylene glycol (PEG). Several animal studies have illustrated PEG’s potential to help prevent axon loss after peripheral nerve injury. However, the relative rate of success and potential complications of these studies have not been definitively shown in the literature. The purpose of this systematic review is to evaluate the literature regarding the success of PEG adjunct treatment after peripheral nerve injury in preclinical models.

Materials and Methods: The MEDLINE database was queried using the PubMed search engine with the following keywords and phrases: “polyethylene glycol” OR “PEG” AND “nerve” AND “fusion”. All resulting articles were screened by two reviewers. Animal type, nerve type, injury type, type(s) of analyses, and overall superiority of outcomes were assessed.

Results: One-hundred and seventy-nine articles were identified, and thirteen studies remained after the application of inclusion and exclusion criteria. Twelve of the thirteen studies utilized rats as the preclinical model, while one utilized a guinea pig. Superiority of peripheral nerve repair outcomes with adjunct PEG treatment compared to a control group was reported in eleven of thirteen studies.

Conclusions: The majority of studies reported positive outcomes when using PEG; this indicates that PEG treatment has the potential to enhance peripheral nerve regeneration after injury. However, the results of some of these studies indicated several uncertainties that need to be addressed in future studies. These preclinical models may help guide clinicians regarding the use of PEG treatment in peripheral nerve repair.

DOI: 10.29245/2572.942X/2021/1.1280 View / Download Pdf
Vol 6-1 Original Research Article

Classification of Trauma-Related Outcomes in US Veterans Using Magnetoencephalography (MEG)

Lisa M. James1,2,3,4, Brian E. Enghdal1,2,4,5,, Arthur C. Leuthold1,2, Apostolos P. Georgopoulos1,2,3,4,6*

1The PTSD Research Group, Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

4Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

5Department of Psychology, University of Minnesota, Minneapolis, MN, USA

6Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, USA

Previous research has demonstrated highly accurate classification of veterans with posttraumatic stress disorder (PTSD) and controls based on synchronous neural interactions (SNI), highlighting the utility of SNI as a biomarker of PTSD. Here we extend that research to classify additional trauma-related outcomes including subthreshold PTSD, partial recovery, and full recovery according to SNI. A total of 219 U.S. veterans completed diagnostic interviews and underwent a magnetoencephalography (MEG) scan from which SNI was computed. Linear discriminant analysis was used to classify the PTSD and control brains, achieving 100% accuracy. That discriminant function was then used to classify each brain in the subthreshold PTSD, partial recovery, and full recovery diagnostic groups as PTSD or Control. All of the subthreshold PTSD diagnostic group were classified as PTSD, as were three-quarters of the partial recovery group. Findings regarding the full recovery group were mixed, documenting variability in the functional brain status of PTSD recovery. The results of the present study add to the literature supporting the discriminatory power of MEG SNI and demonstrate the utility of SNI as a biomarker of various PTSD-related trajectories.

DOI: 10.29245/2572.942X/2021/1.1279 View / Download Pdf
Vol 6-1 Research Article

Emotional, Behavioral, and Cognitive Correlates of Attention Deficit and Hyperactive Disorder (ADHD) Screening and Diagnosis History: Sex/Gender Differences

Shervin Assari1,2*

1Department of Urban Public Health, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

2Department of Family Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

Background: While clinical studies have documented sex differences in emotional, behavioral, and cognitive function of children with Attention Deficit and Hyperactive Disorder (ADHD), it is unknown if these sex differences are due to differences in referral and diagnosis or if they can be also seen when we screen a community sample for ADHD. If these sex differences exist in populations with a diagnosis history but cannot be seen in screening, then they are unfair, preventable, and due to gender (social processes in referral and diagnosis) rather than sex.

Aim:Using the data from a community sample of 9-10-year-old healthy developing children, we explored sex differences in the associations between cognitive, emotional, behavioral, and health status with positive screening vs. history of diagnosed ADHD.

Methods: The Adolescent Brain Cognitive Development (ABCD) study included a national sample of 10,171 American children between ages 9 and 10 years old. This sample included 1,488 children with a history of psychiatric diagnosis and 8,683 children without a diagnosis. The two independent variables were screening and history of ADHD. The following variables were outcomes: symptom severity, cognitive function, body mass index (BMI), internalizing, externalizing, and total behavioral disorders. Sex was the moderator, and age, race, ethnicity, education, household income, and family structure were covariates. Mixed-effects regression models were used to adjust for the nested nature of the data.

Results: Positive screening for ADHD and a history of diagnosis were both associated with worse cognitive function, higher internalizing, externalizing, total problem behaviors, higher inattention (ADHD symptoms), and lower BMI. Sex altered the association between history of diagnosis but not positive screening for ADHD with externalizing, and total behavioral problems as well as cognitive function. Sex did not affect the associations between positive screening for ADHD or a history of diagnosis with BMI or ADHD symptoms. Both history of diagnosis and positive screening for ADHD were associated with higher internalizing for boys than girls.

Conclusion: History of diagnosis, but not positive screening for ADHD, is differently associated with behavioral and cognitive performance of males and females. As sex differences are seen in correlates of history of diagnosis but not positive screening, some of the observed sex differences are due to differential referral and diagnosis rather than differential presentation of ADHD in the community. This finding suggests that some of the so-called “sex differences” that are believed to be due to biology and heritable may be “gender differences” and modifiable. This is important because while gender differences are preventable and modifiable, sex differences are not.

DOI: 10.29245/2572.942X/2021/1.1278 View / Download Pdf
Vol 6-1 Original Research Article

Protective Effect of Stem Cells from Toxicity Induced by Gulf War Illness (GWI) Serum in N2A Neuroblastoma Cells

Effie-Photini C. Tsilibary1,2, Danielle Carlson1,2, Apostolos P. Georgopoulos1,2*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, Minnesota, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, Minnesota, USA

Gulf War Illness (GWI) afflicted many veterans of the 1990-91 Gulf War with multiple symptoms worsening with time. The reasons for GWI have not been elucidated but may include toxicity due to inflammatory factors induced by vaccines administered to deployed and nondeployed veterans. In particular, the anthrax vaccine may have harmful effects in veterans lacking specific protective HLA alleles, as we reported previously, using a murine neuroblastoma N2A cell culture system. Lack of these protective alleles could allow several vaccine antigens to circulate chronically, resulting in protracted low-grade inflammation accompanying the disease. When N2A cells were exposed to GWI serum or the antigen of the anthrax vaccine, the cells underwent apoptosis due to compromised cell membrane, mitochondrial and cytoskeletal function.  Elucidation of mechanisms of GWI should provide clues for therapy. Since antigen-induced inflammation accompanies GWI and stem cells were reported to have antimicrobial activity, we examined the effect of murine stem cells co-cultured with N2A cells before exposure to GWI serum and also Protective Antigen PA63, the main component of the anthrax vaccine. The presence of stem cells completely prevented GWI serum toxicity, since it resulted in inhibition of apoptosis. Moreover, cultures of stem cells exposed to PA63 resulted in the degradation of this antigen. We conclude that stem cells can protect against vaccine-induced toxic components of the GWI serum in N2A cells, prompting further studies on the possible beneficial effects of these cells in GWI.

DOI: 10.29245/2572.942X/2021/1.1281 View / Download Pdf