Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury

Introduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI).

Method: Fifty-six male U.S. Veterans (M_Age = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (?FrSBe). Linear regression models examined variables predicting ?FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist–Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test).

Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function.

Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.     

Marked hypodiploidy in blast phase chronic myelogenous leukemia: report of a case and review of the literature

The emergence of a near-haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients.     

中等强度冲击波负压暴露对豚鼠耳蜗毛细胞游离钙浓度的影响

目的:观察实验性冲击波负压(BUP)暴露对豚鼠耳蜗外毛细胞内游离钙浓度([Ca2 ]i)的影响。方法:在激光共聚焦显微镜下,用钙敏荧光探针Fluo-3作为指示剂,观察豚鼠暴露中等强度实验性BUP后耳蜗外毛细胞[Ca2 ]i的变化。结果:中等强度BUP暴露后8 h,至暴露后24 h和3 d稍有回落,但仍高于正常对照组。上述这些变化与听性脑干反应阈值的升高是一致的。结论:豚鼠暴露中等强度性BUP可引起耳蜗外毛细胞内[Ca2 ]i的明显增高,且可能是听功能损害的主要原因之一。     

Comparative observation of protective effects of earplug and barrel on auditory organs of guinea pigs exposed to experimental blast underpressure

Objective: To explore the protective effects of earplug and barrel on auditory organs of guinea pigs exposed to experimental blast underpressure (BUP). Methods : The hearing thresholds of the guinea pigs were assessed with auditory brainstem responses ( ABR). The traumatic levels of tympanic membrane and ossicular chain were observed under stereo-microscope. The rate of outer hair cells (OHCs) loss was analyzed using a light microscope. The changes of guinea pigs protected with barrel and earplug were compared with those of the control group without any protection. Results: An important ABR threshold shift of the guinea pigs without any protection was detected from 8h to 14d after being exposed to BUP with a peak ranging from -64.5 kPa to -69.3 kPa (P<0.01). The rate of perforation of tympanic membrane reached 87.5 % and that of total OHCs loss was 19.46%±5.38% at 14d after exposure. The guinea pigs protected with barrel and earplug had lower ABR threshold and total OHCs loss rate compared with the animals without any protection (P<0.01). All of the tympanic membrane and ossicular chain of the protected animals maintained their integrities. Meanwhile, the guinea pigs protected with the barrel had lower ABR threshold and total OHCs loss rate than those with earplug (P<0.01). Conclusions: The earplug and barrel have protective effects against BUP-induced trauma on auditory organs of the guinea pigs and the protective effects of barrel are better than those of earplug.     

骨髓增生异常综合症几项实验指标研究进展

本文对MDS染色体、骨髓祖细胞体外培养及免疫功能几项实验指标的研究进展予以介绍。     

火药爆炸复合烧伤大鼠血浆CK-MB与心肌MDA变化

目的 探讨烟花火药爆炸复合烧伤大鼠血浆肌酸激酶心肌同工酶(CK—MB)与心肌丙二醛(MDA)含量的变化。方法 Wistar大鼠128只，随机分为正常对照组(n=8)、烧伤组(n=40)、爆炸伤组(n=40)和复合伤组(n=40)，分别致伤形成大鼠20％体表面积Ⅲ度烧伤、火药爆炸伤和两者复合伤。动态观察大鼠伤后1、3、6、12、24h血浆CK—MB，心肌MDA含量并进行相关分析。结果 复合伤组较单因素致伤组大鼠血浆CK—MB升高明显，心肌组织MDA含量呈类似变化，CK—MB与MDA有相关性。结论 烟花火药爆炸复合烧伤对大鼠心肌的损害较单纯烧伤或爆炸伤更为严重，提示烧伤和爆炸伤有协同致伤作用，氧自由基代谢紊乱参与烟花火药爆炸复合烧伤后心肌的损伤。     

Adenovirus-mediated human β-nerve growth factor gene transfer has a protective effect on cochlear spiral ganglion after blast exposure

Objective：To study whether adenovirus-mediated human β-nerve growth factor （Ad-hNGFβ） gene has any protective effect on blast hearing impairment. Methods：Deafness was induced by blast exposure （172.0 dB） in 30 healthy guinea pigs. On day 7 of blast exposure, Ad-hNGFβ was infused into the perilymphatic space of 20 animals as the study group （hNGFβ group）, and artificial perilymph fluid （APF） was infused into the perilymphatic space of the other 10 animals as the control group. At weeks 1, 4 and 8 after blast exposure, the animals were sacrificed and the cochleae were removed for immunohistochemical and HE stainings. Results： Expression of Ad-hNGFβ protein was detected in each turn of the cochlea at the 1st week, with almost equal intensity in all turns. At the 4th week, the reactive intensity of the expression of Ad-hNGFβ protein decreased. At the 8th week, no expression was detectable. The results of HE staining showed that the amount of spiral ganglions in hNGFβ group was significantly greater than that of the control group at week 4 （P〈0.01）. Conclusion： Ad-hNGFβ can be expressed at a high level and for a relatively long period in the blast impaired cochlea, suggesting that Ad-hNGFβ has a protective effect on cochlear spiral ganglion cells after blast exposure and the efficient gene transfer into cochlea had been achieved without toxicity.     

Recombinant human colony stimulating factor-granulocyte/macrophage and -granulocyte,but not macrophage induce the development of a respiratory burst in primary human myeloid leukemic cells in vitro

Summary Respiratory burst develops in myeloid blast cells if they differentiate functionally along the monocytic or granulocytic lineage. Using the nitroblue tetrazolium (NBT) assay we studied the effects of recombinant human granulocyte/macrophage colony stimulating factor (rhuGM-CSF), rhuG-CSF and rhuM-CSF on development of respiratory burst activity in primary blast cells from patients with myeloid leukemia. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (AML, n=13) or myeloidblast crisis (myBC) of chronic myeloid leukemia (CML, n=5) it was found that the percentage of NBT positive cells was increased by at least 20% as compared to control cultures by rhuGM-CSF in 6/17 cases, by rhuG-CSF in 7/17 cases and by rhuM-CSF in 0/16 cases, representing in responders a mean increase of 267% and 270% in the absolute number of NBT positive cells by rhuGM-CSF and rhuG-CSF, respectively. Morphological examination of cultured cells from responders, as compared to controls, showed decreased blast cell content but generally no evidence of terminal differentiation. The demonstration of Auer rods in NBT positive cells indicates that respiratory burst developed in a leukemic clone. These findings may be of physiological, pathophysiological and clinical relevance.