OBJECTIVES: To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism. METHODS: A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats. RESULTS: Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05). CONCLUSIONS Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.
Animals ; Female ; Pregnancy ; Rats ; Body Weight ; Brain Injuries/prevention & control* ; Caspase 1 ; Inflammation/drug therapy* ; Interleukin-6 ; Interleukin-8 ; NF-E2-Related Factor 2 ; NLR Family, Pyrin Domain-Containing 3 Protein ; Flavonoids/therapeutic use*

Since December 2019, a pneumonia caused by a new coronavirus, i.e. COVID-19 occurred in Wuhan, Hubei Province, China. Although the epidemic in China has been bought under control, the global COVID-19 situation is still grim. Severe traumatic brain injury (TBI), as one of critical conditions in the department of neurosurgery, requires an early and effective treatment, especially surgery. There were currently no reliable guidelines on how to perform perioperative protection in TBI patients with suspected or confirmed coronavirus infection. According to the corresponding treatment regulations and guidelines issued by the authorities, we summarized the management strategy of TBI patients in perioperative period during the COVID-19 outbreak based on medical and nursing practice, in order to provide a reference for clinicians.
Aged ; Aged, 80 and over ; Anesthesia ; methods ; Betacoronavirus ; Brain Injuries, Traumatic ; surgery ; Coronavirus Infections ; epidemiology ; prevention & control ; Female ; Humans ; Male ; Middle Aged ; Operating Rooms ; Pandemics ; prevention & control ; Perioperative Care ; Pneumonia, Viral ; epidemiology ; prevention & control

OBJECTIVETo investigate the protective effect of prostaglandin E1 (PGE-1) against brain injury induced by hyperoxia in neonatal rats and observe the changes in the expression of glucose-regulated protein 78 (GRP78) and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and to provide a theoretical basis for the clinical application of PGE-1 in the treatment of neonatal brain injury induced by hyperoxia.

METHODSSixty neonatal Wistar rats were randomly divided into air control group, hyperoxic brain injury model group, and hyperoxic brain injury+PGE-1 group. All rats except those in the air control group were treated to establish a hyperoxic brain injury model. From the first day of modeling, the rats in the hyperoxia brain injury+PGE-1 group were intraperitoneally injected with PGE-1 2 μg/kg daily for 7 consecutive days, while the other two groups were treated with normal saline instead. The water content of brain tissue was measured; the pathological changes of brain tissue were evaluated by hematoxylin-eosin staining; the apoptosis of brain cells was assessed by nuclear staining combined with TUNEL staining; the protein expression of GRP78 and CHOP in brain tissue was measured by Western blot.

RESULTSThe water content of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the water content of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P<0.05). The pathological section of brain tissue showed inflammatory cell infiltration and mild cerebrovascular edema in the brain parenchyma in the hyperoxic brain injury model group; the periparenchymal inflammation and edema in the hyperoxic brain injury+PGE-1 group were milder than those in the hyperoxic brain injury model group. The apoptosis index of brain tissue in the hyperoxic brain injury model group was significantly higher than that in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the apoptosis index of brain tissue in the hyperoxic brain injury+PGE-1 group was significantly higher than that in the air control group (P<0.05). The protein expression of GRP78 and CHOP in brain tissue was significantly higher in the hyperoxic brain injury model group than in the hyperoxic brain injury+PGE-1 group and air control group (P<0.05); the protein expression of GRP78 and CHOP was significantly higher in the hyperoxic brain injury+PGE-1 group than in the air control group (P<0.05).

CONCLUSIONSPGE-1 has a protective effect against hyperoxia-induced brain injury in neonatal rats, which may be related to the inhibition of cell apoptosis by down-regulating the expression of GRP78 and CHOP.

Alprostadil ; therapeutic use ; Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Brain ; pathology ; Brain Injuries ; metabolism ; pathology ; prevention & control ; Heat-Shock Proteins ; analysis ; Hyperoxia ; complications ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Wistar ; Transcription Factor CHOP ; analysis

Mesenchymal stem cell (MSC) transplantation is considered one of the most promising therapeutic strategies for the repair of brain injuries and plays an important role in various links of nerve repair. Recent studies have shown that MSC-derived exosomes may dominate the repair of brain injuries and help to promote angiogenesis, regulate immunity, inhibit apoptosis, and repair the nerves, and therefore, they have a great potential in the treatment of brain injuries in neonates. With reference to these studies, this article reviews the mechanism of action of exosomes in the repair of brain injuries and related prospects and challenges, in order to provide new directions for the treatment of brain injuries in neonates with stem cells.
Apoptosis ; Brain Injuries ; therapy ; Exosomes ; physiology ; Humans ; Inflammation ; prevention & control ; Mesenchymal Stem Cell Transplantation ; Neovascularization, Physiologic ; T-Lymphocytes ; immunology

OBJECTIVETo investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.

METHODSAdult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR.

RESULTSAll of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.

CONCLUSIONSince caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

Animals ; Blast Injuries ; complications ; Brain Injuries, Traumatic ; complications ; Caffeine ; pharmacology ; Cerebral Cortex ; pathology ; Hippocampus ; pathology ; Male ; Memory Disorders ; etiology ; prevention & control ; Mice ; Mice, Inbred C57BL ; RNA, Messenger ; analysis ; Receptor, Adenosine A1 ; genetics

With the increasing incidence of blast injury, the research on its mechanisms and protective measures draws more and more attention. Blast injury has many characteristics different from general war injuries or trauma. For example, soldiers often have various degrees of visceral injury without significant surface damage, combined injuries and arterial air embolism. Researchers in China began to investigate blast injury later than the United States and Sweden, but the development is so fast that lots of achievements have been gained, including the development of biological shock tube, the mechanisms and characteristics of blast injury in various organs, as well as protective measures under special environments. This article reviews the past and current situation of blast injury research in China.
Animals ; Blast Injuries ; diagnosis ; etiology ; prevention & control ; therapy ; Brain Injuries, Traumatic ; etiology ; China ; Disease Models, Animal ; Ear ; injuries ; Eye Injuries ; etiology ; High-Energy Shock Waves ; Humans ; Lung Injury ; etiology ; Research

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group (P<0.01), while obviously reduced the MDA and PCO contents and the ROS levels derived from of the brain mitochondria. The shikonin also noticeably improved the spatial memory deficits caused by carbon ion beam irradiation. All results demonstrated that shikonin could improve the irradiated brain injury which might resulted from its modulation effects on the oxidative stress induced by the 12C6+ ion beam.
Animals ; Antioxidants ; pharmacology ; Brain Injuries ; prevention & control ; Catalase ; metabolism ; Heavy Ion Radiotherapy ; Male ; Malondialdehyde ; metabolism ; Mice ; Naphthoquinones ; pharmacology ; Protein Carbonylation ; Radiation Injuries, Experimental ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Random Allocation ; Specific Pathogen-Free Organisms ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the influence of therapeutic bloodletting at Jing-well points and hypothermia on acute cerebral edema after traumatic brain injury (TBI) in rats.

METHODSSeventy-five SD rats were randomly divided into sham-operation group (Sham), TBI group (TBI), bloodletting group (BL), mild-induced hypothermia group (MIH), and bloodletting plus MIH group (BL + MIH) (n = 15). The model of TBI was established by electric controlled cortical impactor (eCCI). The rats of BL group were bloodletting at Jing-well points immediately after injury, twice daily. While the MIH group was settled on a hypothermia blanket promptly after TBI for 6 hours, so that the temperature dropped to 32 degrees. Each of measurement was performed after 48 hours. Magnetic resonance imaging (MRI) was used to evaluate the dynamic impairment of cerebral edema after TBI (n = 3). In addition, mNSS score, measurements of wet and dry brain weight, and Evans Blue assay were performed to investigate the neurologic deficit, cerebral water content (n = 8), and blood-brain barrier permeability (BBB), (n = 4), respectively.

RESULTSMRI analysis showed that the cerebral edema, hematoma and midline shifting of rats in TBI group was more serious than other treatment group. Meanwhile compared with TBI group, the mNSS scores of every treatment group were meaningfully lower (all P < 0.05). Furthermore, treatment with BL+ MIH group was superior to the separated BL and MIH group (all P < 0.01). In addition, brain water content of each intervention group reduced to varying degrees (all P < 0.05), especially that of MIH group and BL + MIH group (P <0.01). BBB permeability of each treatment group was also significantly improved (all P < 0.01), and the improvement in MIH group and BL + MIH group was much better than the BL alone group (P < 0.05, P < 0.01).

CONCLUSIONOur major finding is that bloodletting at Jing-well points and MIH can reduce cerebral edema and BBB dysfunction and exert neuroprotective effects after TBI. The results suggest that the combination of BL and MIH is more effective than other treatment being used alone.

Animals ; Blood-Brain Barrier ; Bloodletting ; Brain ; pathology ; Brain Edema ; prevention & control ; Brain Injuries ; therapy ; Hypothermia, Induced ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the factors for hydrocephalus secondary to severe traumatic brain injury after surgery, and to explore a new theory and guideline for clinical early prevention and treatment for hydrocephalus.
 METHODS: The clinical data regarding 107 patients with severe traumatic brain injury, who were admitted to our hospital from June 2010 to June 2013, were analyzed. Logistic multi-factor regression was used to analyze the different factors including ages, gender, the Glasgow coma scale (GCS) score before or after surgery, the situation of ventricular system bleeding secondary to surgery, the situation of midbrain aqueduct and ambient cistern before or after surgery, the relationship between early lumbar puncture and the hydrocephalus. The risk and protective factors for postoperative hydrocephalus were discussed.
 RESULTS: The results showed that patients with low GCS score in pre/postoperative (OR=0.099, 95%CI: 0.028-0.350)/(OR=0.088, 95%CI: 0.012-0.649), ventricular system bleeding in postoperative (OR=0.168, 95%CI: 0.029-0.979) and dim CT image for midbrain aqueduct and ambient cistern (OR=0.134, 95%CI: 0.038-0.473)/(OR=0.221, 95%CI: 0.055-0.882) are risk factors. Whereas lumbar puncture (OR=75.885, 95%CI: 9.612-599.122) is a protective factor for postoperative hydrocephalus in STBI patients. The secondary hydrocephalus was mainly occurred in 2 weeks and 2 weeks to 3 months after operation. The incidence of the control group that occurred secondary hydrocephalus is higher than that of the lumbar puncture group (P<0.05). The secondary hydrocephalus were mainly occurred in 2 weeks and 2 weeks to 3 months after operation, with no statistical significance between the 2 groups after 3 months of operation (P>0.05).
 CONCLUSION For patients with stable vital signs, early lumbar puncture could significantly reduce the incidence of secondary hydrocephalus in acute and subacute stage after severe traumatic brain injury.
Brain Injuries ; complications ; Cerebral Ventricles ; physiopathology ; Glasgow Coma Scale ; Humans ; Hydrocephalus ; etiology ; prevention & control ; Incidence ; Logistic Models ; Risk Factors ; Spinal Puncture ; Treatment Outcome

Brain Injuries ; etiology ; prevention & control ; Humans ; Hyperbilirubinemia ; complications ; prevention & control