Electronic cigarette (e-cigarette) use is on the rise worldwide and is particularly attractive to young people and as a smoking substitute by pregnant woman. There is a perception in pregnant women and women of child-bearing age that the use of e-cigarettes (vaping) is safer than smoking tobacco cigarettes during pregnancy. However, there is little evidence to support this perception. Here, we examined the offspring from mouse dams that had been exposed during and after pregnancy to ambient air (sham) ( n = 8), e-cigarette aerosols with nicotine ( n = 8), or e-cigarette aerosols without nicotine ( n = 8). Offspring underwent cognitive testing at 12 weeks of age and epigenetic testing of brain tissues at 1 day, 20 days, and 13 weeks after birth. The findings showed deficits in short-term memory, reduced anxiety, and hyperactivity in offspring following maternal e-cigarette exposure using the novel object recognition and elevated plus maze tests. In addition, global DNA methylation was increased in the brains of offspring soon after birth. Using a quantitative-PCR array specific to chromatin modification enzymes on genomic DNA and histones,13 key genes were identified to be significantly altered in the offspring brains from the e-cigarette groups compared to the nonexposed groups. The changes to genes Aurka, Aurkb, Aurkc, Kdm5c, Kdm6b, Dnmt3a, Dnmt3b, and Atf2, all associated with modulating neurological activity, were validated using RT-qPCR. In conclusion, in a mouse model, maternal exposure to e-cigarette aerosols resulted in both cognitive and epigenetic changes in offspring. This suggests that the use of e-cigarettes during pregnancy may have hitherto undetected neurological consequences on newborns.
Increasing evidence indicates the potential of olfactory ensheathing cells (OECs) for treating spinal cord injuries. The present study compared proliferation and migration of adult rat and human OECs transplanted into the spinal cord of athymic (immunodeficient) rats. OECs were purified from the nasal lamina propria and prelabeled with a cytoplasmic dye. After OEC injection into the thoracic spinal cord, animals were perfused 4 hr, 24 hr, and 7 days later. Both rat and human OECs showed similar migration. Cells were seen leaving the injection site after 4 hr, and by 7 days both rat and human OECs had migrated approximately 1 mm rostrally and caudally within the cord (rat: 1,400 +/- 241 microm rostral, 1,134 +/- 262 microm caudal, n = 5; human: 1,337 +/- 192 microm rostral, 1,205 +/- 148 microm caudal, n = 6). Proliferation of transplanted OECs was evident at 4 hr, but most had ceased dividing by 24 hr. In 10 animals, the spinal cord was injured by a contralateral hemisection made 5 mm rostral to the transplantation site at the time of OEC transplantation. After 7 days, macrophages were numerous both around the injury and at the transplantation site. In the injured cord, rat and human OECs migrated for shorter distances, in both rostral and caudal directions (rat: 762 +/- 118 microm rostral, 554 +/- 142 microm caudal, n = 4; human: 430 +/- 55 microm rostral, 399 +/- 161 microm caudal, n = 3). The results show that rat and human OECs rapidly stop dividing after transplantation and have a similar ability to survive and migrate within the spinal cord of immunocompromised hosts. OECs migrated less in animals with a concomitant contralateral hemisection.
The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of this study was to assess locomotor recovery and tissue morphology after SCI in athymic (nude) rats, in which T-cell numbers are reduced. Results in athymic rats were compared with heterozygote littermates with normal T-cell profiles and with Sprague-Dawley rats from previous studies in our lab. Following transection of rat spinal cords at T10, we assessed the animals' locomotor recovery on a weekly basis for up to 11 weeks, using the Basso-Beattie-Bresnahan locomotor rating scale. Nude rats showed better locomotor recovery than did heterozygote or Sprague-Dawley rats, achieving scores of 5.6 +/- 0.8 versus 1.0 +/- 0.0, respectively (p = 0.002), at 4 weeks postinjury. The improved recovery of nude rats persisted for the 11-week postinjury assessment period, and was consistent with improved spinal reflexes rather than with recovery of descending motor pathways. Anatomical evaluation at 11 weeks indicated no difference in nude versus heterozygote rats in the size or distribution of cavities caudal to the transection site, but secondary damage was more severe rostral to the transection site in heterozygote rats. In neither group did cavities extend beyond 4 mm caudal to the transection site, and were therefore not directly responsible for the functional differences between the two groups. Cellular expression of the microglia/macrophage antigen ectodysplasin A (ED1) was reduced in nude rats as compared to heterozygotes, but no difference was observed in expression levels of 5-hydroxytryptamine, the 200-kDa neurofilament, or glial fibrillary acidic protein. The findings of the study show that a reduction in T-cell numbers significantly improves locomotor recovery after spinal cord transection, indicating a deleterious role for these immune cells in neural repair after trauma.
The brains of 32 children (3 months to 16 years) who died as a result of motor vehicle collisions were examined for axonal injury using beta-APP immunohistochemistry. The extent and distribution of axonal injury was assessed and quantified throughout the forebrain, brainstem and cerebellum. The mean diameter of immunoreactive axons in the corpus callosum was measured for this pediatric group and, for comparison, a small adult sample. beta-APP immunoreactivity was seen in 14 pediatric cases (survival 35 mins to 87 h), most frequently in the parasagittal white matter (12/14), the corpus callosum (11/14), the brainstem (10/14) and cerebellum (9/14). In 2 cases, axon swelling was visualized in the internal capsule after only 35-45-min survival, earlier than has previously been reported. No immunoreactivity was seen in the remaining 18 cases who died within 1 h. The extent and distribution of axonal injury throughout the brain showed a rapid early increase with increasing survival time and then a slower progression. The diameter of individual callosal axons increased with increasing survival times, rapidly over the first 24 h and then more slowly. There was no statistical difference (p < 0.05) for callosal axon diameters at different survival times between the children and the adults sampled here. The extent and distribution of axonal injury throughout the brain appears to be similar in children to that previously reported in adults. The spatial and temporal spread of axonal damage suggests there may be therapeutic potential for the process to be arrested or slowed in its early stages.
These findings suggest that besides age, education, and genetic factors, other vascular risk factors were not associated with AD-related neuropathological changes and urge prompt actions be taken against cerebral small vessel diseases since evidence for effective prevention is still lacking.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.