OBJECTIVE: To summarize the research progress on the mechanism related to traumatic brain injury (TBI) to promote fracture healing, and to provide theoretical basis for clinical treatment of fracture non-union. METHODS: The research literature on TBI to promote fracture healing at home and abroad was reviewed, the role of TBI in fracture healing was summarized from three aspects of nerves, body fluids, and immunity, to explore new ideas for the treatment of fracture non-union. RESULTS: Numerous studies have shown that fracture healing is faster in patients with fracture combined with TBI than in patients with simple fracture. It is found that the expression of various cytokines and hormones in the body fluids of patients with fracture and TBI is significantly higher than that of patients with simple fracture, and the neurofactors released by the nervous system reaches the fracture site through the damaged blood-brain barrier, and the chemotaxis and aggregation of inflammatory cells and inflammatory factors at the fracture end of patients with combined TBI also differs significantly from those of patients with simple fracture. A complex network of humoral, neural, and immunomodulatory networks together promote regeneration of blood vessels at the fracture site, osteoblasts differentiation, and inhibition of osteoclasts activity. CONCLUSION TBI promotes fracture healing through a complex network of neural, humoral, and immunomodulatory, and can treat fracture non-union by intervening in the perifracture microenvironment.
Humans ; Fracture Healing/physiology* ; Brain Injuries/metabolism* ; Brain Injuries, Traumatic ; Fractures, Bone ; Osteogenesis

The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on β-amyloid protein 25-35(Aβ_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aβ_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of β-amyloid protein 1-42(Aβ_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aβ_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol with β-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aβ_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aβ_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aβ_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aβ_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aβ_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.
Mice ; Male ; Animals ; Alzheimer Disease/drug therapy* ; Amyloid beta-Peptides/metabolism* ; Cornus/metabolism* ; Neuroinflammatory Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6 ; Aspartic Acid ; Cysteine/therapeutic use* ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Brain Injuries ; Peptide Hydrolases ; Disease Models, Animal ; Mice, Transgenic

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.
Mice ; Animals ; Male ; Semen/metabolism* ; Gastrointestinal Microbiome ; Network Pharmacology ; Linoleic Acid ; Molecular Docking Simulation ; Alzheimer Disease/genetics* ; Brain Injuries

PURPOSE: Despite advances in modern medicine, traumatic brain injuries (TBIs) are still a major medical problem. Early diagnosis of TBI is crucial for clinical decision-making and prognosis. This study aims to compare the predictive value of Helsinki, Rotterdam, and Stockholm CT scores in predicting the 6-month outcomes in blunt TBI patients. METHODS: This cohort study was conducted on blunt TBI patients of 15 years or older. All of them were admitted to the surgical emergency department of Shahid Beheshti Hospital in Kashan, Iran from 2020 to 2021 and had abnormal trauma-related findings on brain CT images. The patients' demographic data such as age, gender, history of comorbid conditions, mechanism of trauma, Glasgow coma scale, CT images, length of hospital stay, and surgical procedures were recorded. The Helsinki, Rotterdam, and Stockholm CT scores were simultaneously determined according to the existing guidelines. The included patients' 6-month outcome was determined using the Glasgow outcome scale extended. M Data were analyzed by SPSS software version 16.0. Sensitivity, specificity, negative/positive predictive value and the area under the receiver operating characteristic curve were calculated for each test. The Kappa agreement coefficient and Kuder Richardson-20 were used to compare the scoring systems. RESULTS: Altogether 171 TBI patients met the inclusion and exclusion criteria, with the mean age of (44.9 ± 20.2) years. Most patients were male (80.7%), had traffic related injuries (83.1%) and mild TBIs (64.3%). Patients with lower Glasgow coma scale had higher Helsinki, Rotterdam, and Stockholm CT scores and lower Glasgow outcome scale extended scores. Among all the scoring systems, the Helsinki and Stockholm scores showed the highest agreement in predicting patients' outcomes (kappa = 0.657, p < 0.001). The Rotterdam scoring system had the highest sensitivity (90.1%) in predicting death of TBI patients, whereas the Helsinki scoring system had the highest sensitivity (89.8%) in predicting the 6-month outcome in TBI patients. CONCLUSION The Rotterdam scoring system was superior in predicting death in TBI patients, whereas the Helsinki scoring system was more sensitive in predicting the 6-month outcome.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; Aged ; Female ; Cohort Studies ; Tomography, X-Ray Computed/methods* ; Brain Injuries, Traumatic/diagnosis* ; Brain Injuries ; Prognosis ; Glasgow Coma Scale ; Wounds, Nonpenetrating/diagnostic imaging* ; Brain

OBJECTIVE: To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). METHODS: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. RESULTS: The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. CONCLUSION Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).
Humans ; Electroacupuncture ; Lipopolysaccharides ; Single-Blind Method ; Acupuncture Therapy ; Brain Injuries, Traumatic/therapy*

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

Humans ; Spinal Cord Injuries/complications* ; Paralysis/etiology* ; Nervous System Diseases ; Brain

OBJECTIVE: To observe the awakening effect and safety of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture on consciousness disorder in children with early severe traumatic brain injury (STBI) based on western medicine treatment. METHODS: A total of 62 children with STBI were randomly divided into an observation group (31 cases,1 case dropped off) and a control group (31 cases, 1 case dropped off). The control group was treated with routine rehabilitation therapy (6 times a week for 30 days), and intravenous drip of cattle encephalon glycoside and ignotin injection (once a day for 28 days). On the basis of the treatment in the control group, the observation group was treated with Xingnao Kaiqiao acupuncture at Neiguan (PC 6), Shuigou (GV 26), Yintang (GV 24⁺), Baihui (GV 20), Sanyinjiao (SP 6), Zusanli (ST 36), etc., and supplementary acupoints according to clinical symptoms, once a day, 6 times a week for 30 days. The scores of Glasgow coma scale (GCS), coma recovery scale-revised (CRS-R) and modified Barthel index (MBI) were observed before treatment and 10, 20 and 30 d into treatment. Electroencephalogram (EEG) grading before and after treatment was observed in the two groups, and safety was evaluated. RESULTS: After 10, 20 and 30 days of treatment, the scores of GCS, CRS-R and MBI in the two groups were increased compared before treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). After treatment, EEG grading of both groups was improved compared with that before treatment (P<0.05), and the observation group was better than the control group (P<0.05). There were no adverse events or adverse reactions in the two groups during treatment. CONCLUSION On the basis of western medicine treatment, Xingnao Kaiqiao acupuncture plays a remarkable role in wakening the early STBI children, can improve the level of consciousness disorder and daily living ability, and it is safe and effective.
Acupuncture Points ; Acupuncture Therapy ; Brain ; Brain Injuries, Traumatic/therapy* ; Consciousness Disorders/therapy* ; Humans ; Child

Radiation-induced brain injury is a serious complication after cranio-cerebral radiotherapy, which affects the patient's quality of life and survival. A large number of studies have shown that various mechanisms such as neuronal apoptosis, blood-brain barrier damage, and synaptic dysfunction may be related to radiation-induced brain injury. Acupuncture has an important role in clinical rehabilitation of various brain injuries. As a new type of acupuncture, electroacupuncture has the characteristics of strong control ability, uniform and long-lasting stimulation, and is widely used in clinic. This article reviews the effects and mechanisms of electroacupuncture on radiation-induced brain injury, in order to provide a theoretical basis and experimental support for reasonable clinical application.
Humans ; Electroacupuncture ; Quality of Life ; Brain ; Brain Injuries ; Blood-Brain Barrier

OBJECTIVES: To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading. METHODS: A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method. RESULTS: A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (r_s=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05). CONCLUSIONS The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.
Infant, Newborn ; Humans ; Hypoxia-Ischemia, Brain/diagnostic imaging* ; Retrospective Studies ; Brain Injuries ; Electroencephalography ; ROC Curve