scholarly journals Repetitive Mild Head Trauma Induces Activity-Mediated Lifelong Brain Deficits in a Novel Drosophila Model

2021 ◽  
Author(s):  
Joseph A. Behnke ◽  
Changtian Ye ◽  
Aayush Setty ◽  
Kenneth H. Moberg ◽  
James Q. Zheng

AbstractMild head trauma, including concussion, can lead to chronic brain dysfunction and degeneration but the underlying mechanisms remain poorly understood. Here, we developed a novel head impact system to investigate the long-term effects of mild head trauma on brain structure and function, as well as the underlying mechanisms in Drosophila melanogaster. We find that Drosophila subjected to repetitive head impacts develop long-term deficits, including impaired startle-induced climbing, progressive brain degeneration, and shortened lifespan, all of which are substantially exacerbated in female flies. Interestingly, head impacts elicit an elevation in neuronal activity and its acute suppression abrogates the detrimental effects in female flies. Together, our findings validate Drosophila as a suitable model system for investigating the long-term effects of mild head trauma, suggest an increased vulnerability in brain injury in female flies, and indicate that early altered neuronal excitability may be a key mechanism linking mild brain trauma to chronic degeneration.

Author(s):  
York Williams

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. However, in spite of its widespread application throughout what is considered one of the most plastic and sensitive phases of brain development in children, very little is known to date about its long-term effects on brain structure and function leading well into later adolescence and adulthood. Additionally, there is scant information available to parents, clinicians, and clients with ADD/ADHD about the influence of MPH on brain development. More importantly, recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment. As such, a multimodal treatment with psychodynamic therapies can assist the treatment team to support the development of the client's pro-social skills in addition to medication treatment, thus reducing full reliance on MPH as the primary treatment for ADD/ADHD.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aline M De Souza ◽  
Jonathas Almeida ◽  
Nataliia Shults ◽  
Hong Ji ◽  
Kathryn Sandberg

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.


Author(s):  
Kelly Sarmiento ◽  
Dana Waltzman ◽  
Kelley Borradaile ◽  
Andrew Hurwitz ◽  
Kara Conroy ◽  
...  

Due in part to concern about the potential long-term effects of concussion and repetitive head injuries in football, some programs have implemented tackling interventions. This paper explores youth football coaches’ perception of football safety and their experiences implementing these interventions aimed at athlete safety. Using a qualitative approach, coaches were interviewed by means of a semi-structured protocol that covered: (a) demographics; (b) background and experiences with contact sports; (c) perceived concussion risks and benefits of youth football; (d) experiences with tackling technique; (e) experiences with mouth guard sensors; and (f) personal sources of training related to football safety. Most coaches felt that learning tackling at a young age helped prepare them for their playing later in life and believed that youth should begin playing tackle football at a young age. Coaches were mixed regarding their concerns about the risk for concussion and subconcussive head impacts. Still, most were receptive to changes in rules and policies aimed at making football safer. Findings from this study demonstrate that youth football coaches are important stakeholders to consider when implementing changes to youth football. Understanding coach perceptions and experiences may inform future efforts aimed to educate coaches on rules and policies to make the game safer for youth athletes.


PEDIATRICS ◽  
1976 ◽  
Vol 58 (2) ◽  
pp. 303-303
Author(s):  
Leon Oettinger

The article of the Council on Child Health referring to medication for hyperactive children1 contains several misleading or confusing statements: (1) The hyperkinetic behavior syndrome (minimal brain dysfunction) appears in children of below-average intelligence as well as in children of average or above-average intelligence. This was generally agreed on at a recent meeting in Alta, Utah, where a number of investigators, including Paul Wender and C. K. Conners, were present. In an article presented for the Workshop on Evaluating Long-Term Effects of Stimulant Drug Therapy, I presented data showing that minimal brain dysfunction occurred at essentially all levels of intellect.2


Author(s):  
Orla Moriarty ◽  
Suellen M. Walker

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.


2019 ◽  
Vol 9 (5) ◽  
pp. 433-442 ◽  
Author(s):  
Malon Van den Hof ◽  
Anne Marleen ter Haar ◽  
Matthan W.A. Caan ◽  
Rene Spijker ◽  
Johanna H. van der Lee ◽  
...  

ObjectiveWe aim to give an overview of the available evidence on brain structure and function in PHIV-infected patients (PHIV+) using long-term combination antiretroviral therapy (cART) and how differences change over time.MethodsWe conducted an electronic search using MEDLINE, Embase, and PsycINFO. We used the following selection criteria: cohort and cross-sectional studies that reported on brain imaging differences between PHIV+ of all ages who used cART for at least six months before neuroimaging and HIV-negative controls. Two reviewers independently selected studies, performed data extraction, and assessed quality of studies.ResultsAfter screening 1500 abstracts and 343 full-text articles, we identified 19 eligible articles. All included studies had a cross-sectional design and used MRI with different modalities: structural MRI (n = 7), diffusion tensor imaging (DTI) (n = 6), magnetic resonance spectroscopy (n = 5), arterial spin labeling (n = 1), and resting-state functional neuroimaging (n = 1). Studies showed considerable methodological limitations and heterogeneity, preventing us to perform meta-analyses. DTI data on white matter microstructure suggested poorer directional diffusion in cART-treated PHIV+ compared with controls. Other modalities were inconclusive.ConclusionEvidence may suggest brain structure and function differences in the population of PHIV+ on long-term cART compared with the HIV-negative population. Because of a small study population, and considerable heterogeneity and methodological limitations, the extent of brain structure and function differences on neuroimaging between groups remains unknown.


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