Schisandrin B Inhibits NLRP3 Inflammasome Pathway and Attenuates Early Brain Injury in Rats of Subarachnoid Hemorrhage / 中国结合医学杂志

OBJECTIVE@#To determine whether Schisandrin B (Sch B) attenuates early brain injury (EBI) in rats with subarachnoid hemorrhage (SAH).@*METHODS@#Sprague-Dawley rats were divided into sham (sham operation), SAH, SAH+vehicle, and SAH+Sch B groups using a random number table. Rats underwent SAH by endovascular perforation and received Sch B (100 mg/kg) or normal saline after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evan's blue extravasation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) staining were carried out 24 h after SAH. Immunofluorescent staining was performed to detect the expressions of ionized calcium binding adapter molecule 1 (Iba-1) and myeloperoxidase (MPO) in the rat brain, while the expressions of B-cell lymphoma 2 (Bcl-2), Bax, Caspase-3, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated specklike protein containing the caspase-1 activator domain (ASC), Caspase-1, interleukin (IL)-1β, and IL-18 in the rat brains were detected by Western blot.@*RESULTS@#Compared with the SAH group, Sch B significantly improved the neurological function, reduced brain water content, Evan's blue content, and apoptotic cells number in the brain of rats (P<0.05 or P<0.01). Moreover, Sch B decreased SAH-induced expressions of Iba-1 and MPO (P<0.01). SAH caused the elevated expressions of Bax, Caspase-3, NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in the rat brain (P<0.01), all of which were inhibited by Sch B (P<0.01). In addition, Sch B increased the Bcl-2 expression (P<0.01).@*CONCLUSION@#Sch B attenuated SAH-induced EBI, which might be associated with the inhibition of neuroinflammation, neuronal apoptosis, and the NLRP3 inflammatory signaling pathway.

Relations of neuropeptide Y and heme oxygenase-1 expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy

Abstract Purpose: To investigate the relations of neuropeptide Y (NPY) and heme oxygenase-1 (HO-1) expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty rats pregnant for 15 days were randomly divided into experimental and control groups. The ICP model was established in experimental group. On the 21st day, the blood biochemical test, histopathological examination of pregnant rat liver and fetal brain tissues and immunohistochemical analysis of fetal rat brain tissues were performed. Results: On the 21st day, the alanineaminotransferase, aspartate aminotransferase and total bile acid levels in experimental group were significantly higher than control group (P<0.01). Compared with control group, there was obvious vacuolar degeneration in pregnant rat liver tissue and fetal brain tissue in experimental group. NPY expression in fetal brain tissue was negative in control group and positive in experimental group. HO-1 expression in fetal brain tissue was strongly positive in control group and positive in experimental group. There was significant difference of immunohistochemical staining optical density between two groups (P<0.01). Conclusion: In fetal brain of ICP rats, the NPY expression is increased, and the HO-1 expression is decreased, which may be related to the fetal brain injury.

Research Progress of the Relationship between the Expression of TAR DNA-binding Domain Protein 43 and Brain Injury / 法医学杂志

TAR DNA-binding domain protein 43 （TDP-43） is a highly conserved and widely expressed nuclear protein. Nowadays, the expression of TDP-43 can be found in most neurodegenerative diseases such as Alzheimer's disease, which makes it become a neurodegenerative disease associated marker protein. From the current research status at homeland and abroad, and around the relationship between the expression of TDP-43 and brain injury, this article emphatically probes into the specific expression and function of TDP-43 in acute and chronic brain injury based on the knowledge of its biological characteristics, which aims to explore the feasibility for determining the cause of death and the injury and disability situations by TDP-43 in forensic pathology.

The Role of CBS in Injury Time Estimation after Brain Contusion / 法医学杂志

OBJECTIVES@#To observe the changes of cystathionine β-synthase （CBS） expression in the cerebral cortex after brain contusion at different times.@*METHODS@#An experimental model of traumatic brain injury （TBI） in mice was established by an improved weight-drop device. Then Western blotting and immunohistochemical examination were used to detect the CBS expression in cerebral cortex around injury at different time points （1 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d）.@*RESULTS@#The results of Western blotting revealed that the expression level of CBS was down-regulated and reached its lowest level at the 3rd days after injury, and then restored to normal level after 7 days. The results of immunohistochemistry showed that CBS was present in the normal brain cortex. CBS expression gradually decreased at the 3rd days after injury, and then restored to normal level after 7 days.@*CONCLUSIONS@#CBS has the potential to be a reference index for time estimation after brain contusion in forensic practice.

Relationship between Injury Time and Expressions of EPO and Its Receptors in Rats Brain after Cerebral Injury / 法医学杂志

OBJECTIVE@#To explore the relationship between injury age and expressions of erythropoietin (EPO) and its receptor EPOR in the brain tissue of rats after cerebral injury.@*METHODS@#Seventy-two rats were randomly divided into control group (36 rats) and cerebral injury group (36 rats). The rats were sacrificed at 1, 2, 4, 8, 12, 24 h after cerebral injury (6 rats at each time point) and the brain tissues were extracted. The expressions of mRNA and protein of EPO and EPOR at different time points were detected by real-time fluorescent quantitative PCR and Western bloting.@*RESULTS@#The expressions of EPO and EPOR increased within 24 h after injury. The expressions of mRNA and protein of EPO were related to the injury age, and the correlations were 0.875, 0.911, respectively (P < 0.05). The expressions of mRNA and protein of EPOR were related to the injury age, and the correlation coefficients were 0.936, 0.905, respectively (P < 0.05).@*CONCLUSION@#The expressions of EPO and EPOR increase gradually in the early stage of the rat's cerebral injury, which are associated with the injury age and could be a useful value for estimating injury age.

Progress on Hypoxic-ischemic Brain Damage Associated with CCR2 and CCL2 / 法医学杂志

Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.

The role of necroptosis in neurosurgical diseases

Programmed necrosis or necroptosis is an alternative form of cell death that is executed through a caspase-independent pathway. Necroptosis has been implicated in many pathological conditions. Genetic or pharmacological inhibition of necroptotic signaling has been shown to confer neuroprotection after traumatic and ischemic brain injury. Therefore, the necroptotic pathway represents a potential target for neurological diseases that are managed by neurosurgeons. In this review, we summarize recent advances in the understanding of necroptotic signaling pathways and explore the role of necroptotic cell death in craniocerebral trauma, brain tumors, and cerebrovascular diseases.

Minimally traumatic alveolar ridge augmentation with a tunnel injectable thermo-sensitive alginate scaffold

Injectable bone substitutes and techniques have been developed for use in minimally invasive procedures for bone augmentation. Objective : To develop a novel injectable thermo-sensitive alginate hydrogel (TSAH) as a scaffold to induce bone regeneration, using a minimally invasive tunnelling technique. Material and Methods : An injectable TSAH was prepared from a copolymer solution of 8.0 wt% Poly(N-isopropylacrylamide) (PNIPAAm) and 8.0 wt% AAlg-g-PNIPAAm. In vitro properties of the material, such as its microstructure and the sustained release of recombinant human bone morphogenetic protein-2 (rhBMP-2), were investigated. Then, with the subperiosteal tunnelling technique, this material, carrying rhBMP-2, was injected under the labial periosteum of the maxillary anterior alveolar ridge in a rabbit model. New bone formation was evaluated by means of X-ray, micro-computed tomography (micro-CT), fluorescence labelling, histological study, and immunohistochemistry study. Results : The material exhibited good injectability and thermo-irreversible properties. SEM showed an interconnected porous microstructure of the TSAH. The result of ALP activity indicated sustained delivery of BMP-2 from the TSAH from days 3 to 15. In a rabbit model, both TSAH and TSAH/rhBMP-2 induced alveolar ridge augmentation. The percentage of mineralised tissue in the TSAH/rhBMP-2 group (41.6±3.79%) was significantly higher than in the TSAH group (31.3±7.21%; p<0.05). The density of the regenerating tissue was higher in the TSAH/rhBMP-2 group than in the other groups (TSAH group, positive control, blank control; p<0.05). Conclusions : The TSAH provided convenient handling properties for clinical application. To some extent, TSAH could induce ridge augmentation and mineral deposition, which can be enhanced when combined with rhBMP-2 for a minimally invasive tunnelling injection. .

Expression of caspase-3 and HAX-1 after cerebral contusion in rat / 法医学杂志

OBJECTIVE@#To observe the expression pattern of caspase-3 and HCLS1-associated protein X-1 (HAX-1) at different time after cerebral contusion in rat, and explore the new method for estimating the injury interval.@*METHODS@#The cerebral contusion model was established using adult SD male rats. Then the rats were randomly allocated into 8 groups: 2 h, 6 h, 12 h, 1 d, 3 d, and 7 d after cerebral contusion, sham-operation and normal control. Expression of caspase-3 and HAX-1 protein after cerebral contusion in rat was detected by Western blotting. Laser scanning confocal microscope was used to observe the number of HAX-1 positive cells and TUNEL-stained cells after cerebral contusion.@*RESULTS@#The expression of caspase-3 increased parallelly with the time after cerebral contusion and reached the peak value on 3 d. The expression of caspase-3 decreased gradually and still maintained a high level expression on 7 d (P < 0.05). The expression of HAX-1 positive cell went up after injury, and reached the peak value at 6 h (P < 0.05), then turned down gradually after 12 h and went out of detection after 3 d. The number of TUNEL-stained cells increased obviously at 2 h and reached the peak value on 3 d. The number of TUNEL-stained apoptotic cells decreased gradually and still maintained a high level expression on 7 d (P < 0.05).@*CONCLUSION@#The expression of caspase-3 and HAX-1 after cerebral contusion has time sequential regularity, which may provide new evidence for forensic diagnosis of cerebral contusion interval.

Agmatine Attenuates Brain Edema and Apoptotic Cell Death after Traumatic Brain Injury

Traumatic brain injury (TBI) is associated with poor neurological outcome, including necrosis and brain edema. In this study, we investigated whether agmatine treatment reduces edema and apoptotic cell death after TBI. TBI was produced by cold injury to the cerebral primary motor cortex of rats. Agmatine was administered 30 min after injury and once daily until the end of the experiment. Animals were sacrificed for analysis at 1, 2, or 7 days after the injury. Various neurological analyses were performed to investigate disruption of the blood-brain barrier (BBB) and neurological dysfunction after TBI. To examine the extent of brain edema after TBI, the expression of aquaporins (AQPs), phosphorylation of mitogen-activated protein kinases (MAPKs), and nuclear translocation of nuclear factor-kappaB (NF-kappaB) were investigated. Our findings demonstrated that agmatine treatment significantly reduces brain edema after TBI by suppressing the expression of AQP1, 4, and 9. In addition, agmatine treatment significantly reduced apoptotic cell death by suppressing the phosphorylation of MAPKs and by increasing the nuclear translocation of NF-kappaB after TBI. These results suggest that agmatine treatment may have therapeutic potential for brain edema and neural cell death in various central nervous system diseases.

Effects of Repetitive Transcranial Magnetic Stimulation on Behavioral Recovery during Early Stage of Traumatic Brain Injury in Rats

Repetitive transcranial magnetic stimulation (rTMS) is a promising technique that modulates neural networks. However, there were few studies evaluating the effects of rTMS in traumatic brain injury (TBI). Herein, we assessed the effectiveness of rTMS on behavioral recovery and metabolic changes using brain magnetic resonance spectroscopy (MRS) in a rat model of TBI. We also evaluated the safety of rTMS by measuring brain swelling with brain magnetic resonance imaging (MRI). Twenty male Sprague-Dawley rats underwent lateral fluid percussion and were randomly assigned to the sham (n=10) or the rTMS (n=10) group. rTMS was applied on the fourth day after TBI and consisted of 10 daily sessions for 2 weeks with 10 Hz frequency (total pulses=3,000). Although the rTMS group showed an anti-apoptotic effect around the peri-lesional area, functional improvements were not significantly different between the two groups. Additionally, rTMS did not modulate brain metabolites in MRS, nor was there any change of brain lesion or edema after magnetic stimulation. These data suggest that rTMS did not have beneficial effects on motor recovery during early stages of TBI, although an anti-apoptosis was observed in the peri-lesional area.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Language-specific Dysgraphia in Korean Patients with Right Brain Stroke: Influence of Unilateral Spatial Neglect

The purpose of the present study was to investigate the relationship between Korean language-specific dysgraphia and unilateral spatial neglect in 31 right brain stroke patients. All patients were tested for writing errors in spontaneous writing, dictation, and copying tests. The dysgraphia was classified into visuospatial omission, visuospatial destruction, syllabic tilting, stroke omission, stroke addition, and stroke tilting. Twenty-three (77.4%) of the 31 patients made dysgraphia and 18 (58.1%) demonstrated unilateral spatial neglect. The visuospatial omission was the most common dysgraphia followed by stroke addition and omission errors. The highest number of errors was made in the copying and the least was in the spontaneous writing test. Patients with unilateral spatial neglect made a significantly higher number of dysgraphia in the copying test than those without. We identified specific dysgraphia features such as a right side space omission and a vertical stroke addition in Korean right brain stroke patients. In conclusion, unilateral spatial neglect influences copy writing system of Korean language in patients with right brain stroke.

Brain damage and congenital cataract due to autogenously fecal peritonitis in pregnant Wistar rats

PURPOSE: To investigate the morphological aspects of brain and eyes in newborn rats whose mother underwent autogenously fecal peritonitis. METHODS: Four pregnant rats that underwent fecal peritonitis, with a 10% fecal suspension in dose of 4 ml per kilogram received two antimicrobial treatments: 1. intraperitoneal moxifloxacin and dexamethazone; and 2. Intravenous meropenem. After head inspection, the brain consistencies and the eyes belonging to all offspring were analyzed. RESULTS: The brains of newborn from rats that received 4 ml/kg of 10% suspension of feces showed, significantly smaller and less than the firm consistency of those in the control group. Congenital cataract was observed in 9 (34.6%). No cataract was observed in the 20 newborn rats from the mothers that received the combination of moxifloxacin and dexamethasone. Cataract could be observed in three (13.6%) offspring from mothers that received meropenem. CONCLUSIONS: Peritonitis can produce brain damage and congenital cataract in rats. The translation to humans is that intra abdominal infection in pregnant women may be associated with damage in brain and eye structures of their concepts. This can be averting using the adequate early therapeutically approach. .

Shock, diaschisis and von Monakow / Choque, diasquise e von Monakow

The concept of shock apparently emerged in the middle of the 18th century (Whyett) as an occurrence observed experimentally after spinal cord transection, and identified as "shock" phenomenon one century later (Hall). The concept was extended (Brown-Séquard) and it was suggested that brain lesions caused functional rupture in regions distant from the injured one ("action à distance"). The term "diaschisis" (von Monakow), proposed as a new modality of shock, had its concept broadened, underpinned by observations of patients, aiming at distinguishing between symptoms of focal brain lesions and transitory effects they produced, attributable to depression of distant parts of the brain connected to the injured area. Presently, diaschisis is related mainly to cerebrovascular lesions and classified according to the connection fibers involved, as proposed by von Monakow. Depression of metabolism and blood flow in regions anatomically separated, but related by connections with the lesion, allows observing diaschisis with neuroimaging.

O conceito de choque aparentemente surgiu em meados do século 18 (Whyett), como ocorrência observada experimentalmente após seção transversa da medula, e foi identificado como fenômeno de "choque" um século mais tarde (Hall). O conceito foi estendido (Brown-Séquard) e sugeriu-se que lesões cerebrais produziam ruptura funcional em regiões distantes à da lesão ("action à distance"). O termo "diásquise" (von Monakow), proposto como nova modalidade de choque, teve seu conceito ampliado, fundamentado em observações em pacientes. Visava distinguir sintomas de lesões cerebrais focais de efeitos transitórios que produziam, atribuíveis à depressão de partes distantes do cérebro conectadas à área lesada. Atualmente, diásquise é relacionada principalmente a lesões cerebrovasculares e classificada de acordo com as fibras de conexão envolvidas, como proposto por von Monakow. Depressão do metabolismo e fluxo sanguíneo em regiões anatomicamente separadas, mas relacionadas por conexões à lesão, permitem observar diásquise por meio de neuroimagem.

Metallothionein-I/II in brain injury repair mechanism and its application in forensic medicine / 法医学杂志

Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.

Forensic analysis of 24 dismembered homicide cases in Shanghai / 法医学杂志

OBJECTIVE@#To explore the characteristics of the dismembered homicide cases in Shanghai and to provide the valuable guidance for forensic pathological practices.@*METHODS@#Twenty-four cases of dismembered homicides were selected from 2005 to 2012 in Institute of Forensic Science, Shanghai Public Security Bureau. The general information of the victims and suspects, cause of death, criminal motive, postmortem body parts, tools and information of discarding body parts were retrospectively analyzed.@*RESULTS@#Among the 24 dismembered homicide cases, victims were female in 16 cases, and suspects were male in 23 cases and were acquaintances in 22 cases. The main causes of death were mechanical asphyxia and traumatic brain injury. Most of the criminal motives were emotional disputes. The number of postmortem body parts was commonly from 20 to 30. The tools were mainly sharp instruments, including kitchen knives used in 20 cases. The postmortem body parts were discarded to different transregional areas, mainly using vehicles.@*CONCLUSION@#The dismembered homicide cases in Shanghai show the following characteristics: the number of postmortem body parts is in large quantity; the methods of dismembered corpse are complex and different; the job characteristics of suspects are difficult to determine; the distance from homicide scene is far and the vehicles are commonly used.

Language disorders and brain lesion topography in aphasics after stroke / Distúrbios de linguagem e topografia da lesão cerebral em afásicos após acidente vascular cerebral

Aphasia is a language disorder associated with focal brain lesions. Although the topographic definition of the language area has been widely accepted, there is not necessarily any direct correlation between the lesion site and the manifested symptoms. Objective: To analyze aspects of language in aphasics in relation to lesion topography. Methods: A prospective, descriptive study of qualitative nature was conducted on 31 individuals, aged older than 15 years, with at least three years of schooling, and a confirmed diagnosis of stroke. Language assessment was carried out using the Montreal Toulouse battery (alpha version), Boston naming test, and FAS test. Language test results were compared against lesion topography findings from magnetic resonance imaging. Results: Heterogeneous results were found when comparing topography with aphasia, non-aphasia, and performance on language scales. Conclusion: No direct relationship was evident between lesion topography, aphasia, and language test performance.

Afasia é um distúrbio de linguagem associado à lesão cerebral focal. Embora a área de linguagem tenha uma definição topográfica largamente aceita, não se encontra necessariamente uma correlação direta entre o local da lesão e os sintomas manifestados. Objetivo: Analisar aspectos da linguagem em afásicos e a relação com a topografia da lesão. Métodos: Estudo prospectivo, descritivo e de caráter qualitativo e quantitativo, envolvendo 31 indivíduos com idade acima de 15 anos, escolaridade de três anos ou mais e diagnóstico confirmado de acidente vascular cerebral. Foram empregados para avaliação de linguagem o Protocolo Montreal Toulouse (versão alfa), o Teste de Nomeação do Boston e o Teste FAS. Os dados foram comparados com a topografia da lesão, obtidos por ressonância magnética. Resultados: Foi observada heterogeneidade, quando a topografia foi comparada com afasia, não-afasia e o desempenho nas provas de linguagem. Conclusão: Não observou-se relação direta entre a topografia da lesão, a afasia e o desempenho nas provas de linguagem.

Different expression of TNF-alpha in brain and peripheral organs after cerebral contusion of rats / 法医学杂志

OBJECTIVE@#To compare the expression of tumor necrosis factor-alpha (TNF-alpha) between brain and peripheral organs after cerebral contusion in order to provide the scientific theoretical basis for forensic pathological diagnosis and wound age estimation.@*METHODS@#Brain and peripheral organs including heart, liver, spleen, lung, kidney tissues of 45 SD rats after the cerebral contusion were obtained and TNF-alpha of these tissues were analyzed with immunohistochemistry methods.@*RESULTS@#TNF-alpha was detected at 1 h in brain, reaching maximum at 6 h and 3 d after the cerebral contusion, and then decreased but still kept at high expression level at 7 d. TNF-alpha was detected at 1 h after the cerebral contusion in heart, liver, spleen, lung and kidney tissues. The number of cells expressing TNF-alpha increased gradually, reaching maximum at 3 d after the contusion of brain, and then decreased but still kept at high expression level at 7 d.@*CONCLUSION@#Besides the change of cerebral contusion, this study considered both the brain and peripheral organs. It is helpful for forensic pathological diagnosis and wound age estimation after contusion of brain.

Magnetic resonance diffusion tensor imaging for diagnosis of pyramidal tract damage in rats / 法医学杂志

OBJECTIVE@#To explore the applicability of magnetic resonance diffusion tensor imaging (DTI) for diagnosis of pyramidal tract damage in rats.@*METHODS@#Marmarou's model was set up, followed by DTI scanning at 3, 12, 24 and 72 h post trauma to acquire the dispersion parameter of bilateral pyramidal tracts. Moreover, axonal varicosities per square millimeter and the percentage of positive area of axons demonstrated by beta-amyloid precursor protein (beta-APP) immunostaining were obtained, as well as the mean density and sum density of neurofilament (NF) 68 immunostaining.@*RESULTS@#Axial diffusivity (AD), fraction anisotropy (FA) and relative anisotropy (RA) in the pyramidal tract were significantly and continuously reduced and reached to the bottom at 72h post trauma (P < 0.05) in accord with the gradient of axonal damage verified by beta-APP and NF68 immunostaining. Furthermore, the changes of AD, FA and RA showed a significant negative correlation with the beta-APP immunohistochemical results.@*CONCLUSION@#DTI has important value for early diagnosis in pyramidal tract damage.