Characteristics of traumatic brain injury models:from macroscopic blood flow changes to microscopic mitochondrial changes

Controlled cortical impingement is a widely accepted method to induce traumatic brain injury to establish a traumatic brain injury animal model.A strike depth of 1 mm at a certain speed is recommended for a moderate brain injury and a depth of>2 mm is used to induce severe brain injury.However,the different effects and underlying mechanisms of these two model types have not been proven.This study investigated the changes in cerebral blood flow,differences in the degree of cortical damage,and differences in motor function under different injury parameters of 1 and 2 mm at injury speeds of 3,4,and 5 m/s.We also explored the functional changes and mitochondrial damage between the 1 and 2 mm groups in the acute(7 days)and chronic phases(30 days).The results showed that the cerebral blood flow in the injured area of the 1 mm group was significantly increased,and swelling and bulging of brain tissue,increased vascular permeability,and large-scale exudation occurred.In the 2 mm group,the main pathological changes were decreased cerebral blood flow,brain tissue loss,and cerebral vasospasm occlusion in the injured area.Substantial motor and cognitive impairments were found on day 7 after injury in the 2 mm group;at 30 days after injury,the motor function of the 2 mm group mice recovered significantly while cognitive impairment persisted.Transcriptome sequencing showed that compared with the 1 mm group,the 2 mm group expressed more ferroptosis-related genes.Morphological changes of mitochondria in the two groups on days 7 and 30 using transmission electron microscopy revealed that on day 7,the mitochondria in both groups shrank and the vacuoles became larger;on day 30,the mitochondria in the 1 mm group became larger,and the vacuoles in the 2 mm group remained enlarged.By analyzing the proportion of mitochondrial subgroups in different groups,we found that the model mice had different patterns of mitochondrial composition at different time periods,suggesting that the difference in the degree of damage among traumatic brain injury groups may reflect the mitochondrial changes.Taken together,differences in mitochondrial morphology and function between the 1 and 2 mm groups provide a new direction for the accurate classification of traumatic brain injury.Our results provide reliable data support and evaluation methods for promoting the establishment of standard mouse controlled cortical impingement model guidelines.

Associations of preterm and early-term birth with suspected developmental coordination disorder:a national retrospective cohort study in children aged 3-10 years

Background This study analyzed the motor development and suspected developmental coordination disorder of very and moderately preterm(<34^(+0) gestational age),late preterm(34^(+0)-36^(+6)gestational week),and early-term(37^(+0)-38^(+6) gestational week)children compared to their full-term peers with a national population-based sample in China.Methods A total of 1673 children(799 girls,874 boys)aged 3-10 years old were individually assessed with the Movement Assessment Battery for Children-second edition(MABC-2).The association between gestational age and motor performance of children was analyzed using a multilevel regression model.Results The global motor performance[β=-5.111,95%confidence interval(CI)=-9.200 to-1.022;P=0.015]and bal-ance(β=-5.182,95%CI=-5.055 to-1.158;P=0.003)for very and moderately preterm children aged 3-6 years old were significantly lower than their full-term peers when adjusting for confounders.Late preterm and early-term children showed no difference.Moreover,very and moderately preterm children aged 3-6 years had a higher risk of suspected devel-opmental coordination disorder(DCD)(≤5 percentile of MABC-2 score)when adjusting for potential confounders[odds ratio(OR)=2.931,95%CI=1.067-8.054;P=0.038].Late preterm and early-term children showed no difference in motor performance from their full-term peers(each P>0.05).Conclusions Our findings have important implications for understanding motor impairment in children born at different gestational ages.Very and moderately preterm preschoolers have an increased risk of DCD,and long-term follow-up should be provided for early detection and intervention.