The Official Journal of the International Society for Neurochemistry JNC wileyonlinelibrary.com/journal/jnc The Official Journal of the International Society for Neurochemistry JNC Front cover:Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. We observed unexpected patterns of damage and deficits following increasing numbers of closed-head mTBI in adult female rats. This may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mild traumatic brain injuries do not necessarily result in worsening pathology.Image Content: The image shows high-power (4000×) transmission electron microscopy images within the central portion of the splenium of the corpus callosum which were stitched together to create montages which were used for quantification of the ultrastructure of myelinated axons.Read the full article Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model by
Following mild traumatic brain injury (mTBI), the ionic homeostasis of the central nervous system (CNS) becomes imbalanced. Excess Ca2+ influx into cells triggers molecular cascades, which result in detrimental effects. The authors assessed the effects of a combination of ion channel inhibitors (ICI) following repeated mTBI (rmTBI). Adult female rats were subjected to two rmTBI weight-drop injuries 24 h apart, sham procedures (sham), or no procedures (normal). Lomerizine, which inhibits voltage-gated calcium channels, was administered orally twice daily, whereas YM872 and Brilliant Blue G, inhibiting α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and P2X7 receptors, respectively, were delivered intraperitoneally every 48 h post-injury. Vehicle treatment controls were included for rmTBI, sham, and normal groups. At 11 days following rmTBI, there was a significant increase in the time taken to cross the 3 cm beam, as a sub-analysis of neurological severity score (NSS) assessments, compared with the normal control (p < 0.05), and a significant decrease in learning-associated improvement in rmTBI in Morris water maze (MWM) trials relative to the sham (p < 0.05). ICI-treated rmTBI animals were not different to sham, normal controls, or rmTBI treated with vehicle in all neurological severity score and Morris water maze assessments (p > 0.05). rmTBI resulted in increases in microglial cell density, antioxidant responses (manganese-dependent superoxide dismutase (MnSOD) immunoreactivity), and alterations to node of Ranvier structure. ICI treatment decreased microglial density, MnSOD immunoreactivity, and abnormalities of the node of Ranvier compared with vehicle controls (p < 0.01). The authors’ findings demonstrate the beneficial effects of the combinatorial ICI treatment on day 11 post-rmTBI, suggesting an attractive therapeutic strategy against the damage induced by excess Ca2+ following rmTBI.
Background Peri-urban and urban settings have recently gained more prominence in studies on vector-borne transmission of Trypanosoma cruzi due to sustained rural-to-urban migrations and reports of urban infestations with triatomines. Prompted by the finding of Triatoma infestans across the rural-to-urban gradient in Avia Terai, an endemic municipality of the Argentine Chaco, we assessed selected components of domestic transmission risk in order to determine its variation across the gradient. Methods A baseline vector survey was conducted between October 2015 and March 2016, following which we used multistage random sampling to select a representative sample of T. infestans at the municipal level. We assessed T. cruzi infection and blood-feeding sources of 561 insects collected from 109 houses using kinetoplast DNA-PCR assays and direct enzyme-linked immunosorbent assays, respectively. We stratified triatomines according to their collection site (domestic or peridomestic), and we further categorized peridomestic sites in ecotopes of low- or high-risk for T. cruzi infection. Results The overall adjusted prevalence of T. cruzi-infected T. infestans was 1.8% (95% confidence interval [CI] 1.3–2.3) and did not differ between peri-urban (1.7%) and rural (2.2%) environments. No infection was detected in bugs captured in the urban setting; rather, infected triatomines were mainly collected in rural and peri-urban domiciles, occurring in 8% of T. infestans-infested houses. The main blood-feeding sources of domestic and peridomestic triatomines across the gradient were humans and chickens, respectively. The proportion of triatomines that had fed on humans did not differ between peri-urban (62.5%) and rural (65.7%) domiciles, peaking in the few domestic triatomines collected in urban houses and decreasing significantly with an increasing proportion of chicken- and dog- or cat-fed bugs. The relative odds ratio (OR) of having a T. cruzi infection was nearly threefold higher in bugs having a blood meal on humans (OR 3.15), dogs (OR 2.80) or cats (OR: 4.02) in a Firth-penalized multiple logistic model. Conclusions Trypanosoma cruzi transmission was likely occurring both in peri-urban and rural houses of Avia Terai. Widespread infestation in a third of urban blocks combined with high levels of human–triatomine contact in the few infested domiciles implies a threat to urban inhabitants. Vector control strategies and surveillance originally conceived for rural areas should be tailored to peri-urban and urban settings in order to achieve sustainable interruption of domestic transmission in the Chaco region.
Background: Persisting post-concussion symptoms (PPCS) is a complex, multifaceted condition in which individuals continue to experience the symptoms of mild traumatic brain injury (mTBI; concussion) beyond the timeframe that it typically takes to recover. Currently, there is no way of knowing which individuals may develop this condition. Method: Patients presenting to a hospital emergency department (ED) within 48 h of sustaining a mTBI underwent neuropsychological assessment and demographic, injury-related information and blood samples were collected. Concentrations of blood-based biomarkers neuron specific enolase, neurofilament protein-light, and glial fibrillary acidic protein were assessed, and a subset of patients also underwent diffusion tensor–magnetic resonance imaging; both relative to healthy controls. Individuals were classified as having PPCS if they reported a score of 25 or higher on the Rivermead Postconcussion Symptoms Questionnaire at ~28 days post-injury. Univariate exact logistic regression was performed to identify measures that may be predictive of PPCS. Neuroimaging data were examined for differences in fractional anisotropy (FA) and mean diffusivity in regions of interest. Results: Of n = 36 individuals, three (8.33%) were classified as having PPCS. Increased performance on the Repeatable Battery for the Assessment of Neuropsychological Status Update Total Score (OR = 0.81, 95% CI: 0.61–0.95, p = 0.004), Immediate Memory (OR = 0.79, 95% CI: 0.56–0.94, p = 0.001), and Attention (OR = 0.86, 95% CI: 0.71–0.97, p = 0.007) indices, as well as faster completion of the Trails Making Test B (OR = 1.06, 95% CI: 1.00–1.12, p = 0.032) at ED presentation were associated with a statistically significant decreased odds of an individual being classified as having PPCS. There was no significant association between blood-based biomarkers and PPCS in this small sample, although glial fibrillary acidic protein (GFAP) was significantly increased in individuals with mTBI relative to healthy controls. Furthermore, relative to healthy age and sex-matched controls (n = 8), individuals with mTBI (n = 14) had higher levels of FA within the left inferior frontal occipital fasciculus (t (18.06) = −3.01, p = 0.008). Conclusion: Performance on neuropsychological measures may be useful for predicting PPCS, but further investigation is required to elucidate the utility of this and other potential predictors.
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