Regulation of sleep disorders in patients with traumatic brain injury by intestinal flora based on the background of brain-gut axis.

Objective: This study investigates whether people with sleep disorders following traumatic brain injury exhibit altered intestinal flora. The changes may allow us to gain a better understanding of the role of intestinal flora in patients with sleep disorders after traumatic brain injury, which may give us insights into curing the sleep disorder after traumatic brain injury (TBI). Method: We analyzed the intestinal microbial colony structure in the feces of the 28 patients in the normal sleep group and the sleep disorder group by 16SrDNAsequencing technology. The bioinformatics method was used to analyze the intestinal flora change in the v3-v4 region of patients with biorhythm disorder and to observe the difference between the two groups. Results: Group grouping comparison and analysis of the evolutionary cladistic map showed the intestinal flora of patients with normal sleep after TBI was mainly Bacilli and Lactobacillales, while that of patients with sleep disorders was mainly Lachnospiraceae and Bacteroidales. The histogram of group value distribution by grouping comparison and analysis showed that Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were dominant in the sleep disorder group. A relative abundance map of species with significant differences by group grouping comparison showed the main manifestations of intestinal flora are Firmicutes, Bacilli, Lactobacillales, Streptococcaceae, and Bacteroidetes. The normal sleep group was dominated by Bacilli, Lactobacillales, Streptococcus, and Veillonella, while in the sleep disorder group, Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were the main species. It was found that there were also significant differences in intestinal flora abundance between the two groups after TBI. After statistics processing, it was compared with the normal sleep group, Lactobacillus, Streptococcus, Oribacterium and Rothia, Actinomyces, Streptophyta, TM7-3 bacteria, and Serratia, showing a significant reduction in the sleep disorder group (P < 0.05). However, Odoribacter, Lachnospiraceae, and Bilophila increased significantly (P < 0.05). Conclusion: The sleep disorders of patients after TBI can be closely related to intestinal flora disturbance, and its internal mechanism needs further study. Intestinal flora has the potential to be a new therapeutic target.

Regulation of Circadian Clock Genes on Sleep Disorders in Traumatic Brain Injury Patients.

BACKGROUND: In patients with traumatic brain injury (TBI), whether sleep disorder is associated with disturbances in molecular rhythmicity is unclear. This study aimed to investigate the relationship between abnormal sleep and regulation by circadian rhythms in patients with TBI. METHODS: We sampled buccal cells and human blood samples from patients with TBI diagnosed with sleep disorders and those with normal sleep and investigated differences in the expression levels of Clock, Per2, and Bmal1 between the 2 groups. RESULTS: The expression peaks of Clock, Per2, and Bmal1 were at 12:00. There was a statistically significant difference between the sleep disorder group and the normal sleep group in the level of Clock mRNA expression (P = 0.0003 in oral mucosa and P < 0.0001 in mononuclear cells). There was no significant between-group difference in Bmal1 mRNA expression level (P = 0.1187 in oral mucosa and P = 0.2094 in mononuclear cells). There were significant between-group differences in Per2 mRNA expression levels at 12:00 (P = 0.0102 in oral mucosa and P = 0.0006 in mononuclear cells) and 18:00 (P = 0.0004 in oral mucosa and P = 0.0015 in mononuclear cells) but no significant difference at 24:00 (P = 0.7838 in oral mucosa and P = 0.2808 in mononuclear cells). CONCLUSIONS: Abnormal expression levels of Per2, Clock, and Bmal1 were detected in patients with TBI-related sleep disorders. These novel findings demonstrate disturbances in the molecular clock in TBI patients and have important implications for our understanding of the aberrant rhythms reported in this disease.

Period2 downregulation inhibits glioma cell apoptosis by activating the MDM2-TP53 pathway.

The Period2 (Per2) gene is an essential component of the mammalian circadian clock and is strongly linked to glioma occurrence and its response to radiotherapy. Here, we examined the role of Per2 in the response to X-ray-induced DNA damage in U343 glioma cells and in a mouse cancer model. Following low dose X-ray irradiation, we observed that lowering Per2 expression using RNAi reduces DNA damage and cell death in U343 cells and glioma tissue. Additionally, Per2 was associated with increased TP53 activity and was involved in the DNA damage during TP53-mediated apoptosis. These findings suggest that Per2, a core circadian gene, is not only a tumor suppressor gene but can also be regarded as an upstream regulator of TP53. It thus appears that Per2 is an important inhibitor of tumor growth that acts by increasing TP53 expression, DNA damage repair, and apoptosis.

Circadian genes Per1 and Per2 increase radiosensitivity of glioma in vivo.

Per1 and Per2 play a key role in regulating the circadian rhythm in mammals. We report here that although both genes were expressed with a circadian rhythm in glioma and normal brain tissue in rats, their expression profiles differed in the two types of tissue. In addition, high expression of Per1 and Per2 in glioma tissue was associated with increased sensitivity to x-irradiation. No such sensitizing effect was observed in normal tissue. Our results suggest that Per1 and Per2 expression may increase the efficacy of radiotherapy against glioma by promoting apoptosis.

Surgical treatment of central herniation in severely-head injured patients / 中华创伤杂志

Objective To determine the characteristics of treatment and diagnosis,surgical timing and surgical methods in severely head-injured patients with central herniation.Methods Twenty patients with central herniation caused by contusions and lacerations of the bilateral frontal lobes hospitalized from July 2010 to December 2012 were retrospectively reviewed.There were 11 males and 9 females,at mean age of 42 years (range,18-70 years).Injury was caused by traffic accidents in 15 patients,falls in 3 and fighting events in 2.Eight patients were treated immediately on admission and twelve patients underwent emergency operation.All the operations involved simultaneous bilateral craniectomy for decompression,including bilateral decompressive craniectomy in 6 patients and unilateral decompressive craniectomy in 14 patients.Glasgow Outcome Scale (GOS) and Montreal Cognitive Assessment were used to evaluated outcome evaluation and cognitive impairment respectively.Complications were recorded.Results All patients were followed up for 6-12 months (mean,8 months).According to GOS,good recovery was presented in 10 patients,moderate disability occurred in 6,severe disability in 2,vegetative state in 1,and death in 1.Eleven patients suffered severe mental disorders especially personality change and disturbance of intelligence,and restored after 12 months.Five patients were complicated by epilepsy and two hydrocephalus.Conclusions For central herniation in patients with severe head injury,an emergent surgery is necessary if there exist conscious disturbance and pupil aggravations,hematoma enlargement and significant displacement of midline structure.Timely bilateral balance decompressive craniectomy is effective to reduce the mortality and disability and improve quality of life.