Effects of MCC950 on nerve injury in rats with intracerebral hemorrhage / 中国应用生理学杂志

Objective: To investigate the effects of the pyrin domain-containing protein 3 (NLRP3) inflammasome inhibitor MCC950 on nerve injury in rats with intracerebral hemorrhage(ICH). Methods: Seventy-two SD rats were randomly divided into three groups (n=24): Sham group, ICH group and MCC950 group. ICH group and MCC950 group rats were injected with autogenous non-anticoagulant blood to establish ICH model, and then the rats in MCC950 group were intraperitoneally injected with MCC950 at the dose of 10 mg/kg(2 mg/ml) for 3 days after ICH model was established. Seventy-two hours after the establishment of the model, the forelimb placement test, the corner test and mNSS score were performed to observe the neurological function of the rats with ICH. The volume of hematoma was observed in fresh brain tissue sections. HE staining was used to observe the pathological changes of brain tissue. The dry-wet weight ratio was calculated to evaluate the changes of brain tissue edema. The degeneration of neurons was observed by FJC staining. The neuronal apoptosis was observed by TUNEL staining. The protein expression and activation levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD were determined by Western blot. Results: Compared with sham group, the percentage of successful placement of left forelimb and left turn was decreased significantly (P＜0.01, P＜0.05), mNSS score was increased significantly (P＜0.01) in ICH group. Hematoma volume was increased significantly, the number of microglial cells around the hematoma was increased, the number of neurons was decreased, nerve cell swelled, some cells showed pyknotic necrosis, and the staining was deepened. The water content of the right base was increased significantly (P＜0.05). The number of FJC positive and TUNEL positive cells around the hematoma was increased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were increased significantly (P＜0.01, P＜ 0.05). Compared with ICH group, the percentage of successful placement of left forelimb and left turn was increased significantly in MCC950 group (P＜0.05), while the mNSS score and the volume of hematoma were decreased significantly (P＜0.01), the swelling degree of nerve cells around the hematoma was reduced significantly, and the number of pyrotic necrotic cells was decreased. The water content of the right base was decreased significantly (P＜0.05), and the number of FJC positive and TUNEL positive cells around the hematoma was decreased significantly (P＜0.05). The levels of NLRP3, ASC, caspase-1, pro-caspase-1, caspase-1/pro-caspase-1 ratio, GSDMD-N, GSDMD, GSDMD-N/GSDMD ratio, IL-1β and IL-18 were decreased significantly (P＜0.05). Conclusion: MCC950 can ameliorate nerve injury after ICH by inhibiting NLRP3 inflammasome mediated inflammation and pyroptosis.

Potential drug-drug interactions among patients with spontaneous intracerebral hemorrhage treated at the Neurological Intensive Care Unit: a single-center experience

Abstract Our aim was to determine the prevalence of potential drug-drug interactions (pDDIs) and to identify relevant factors associated with the occurrence of the most dangerous or contraindicated pDDIs (pCDDIs) in hospitalized patients with spontaneous intracerebral hemorrhage (sICH). A retrospective cross-sectional study was performed enrolling all consecutive patients with sICH treated at the Neurological Intensive Care Unit, Clinical Center in Kragujevac, Serbia, during the three-year period (2012-2014). The inclusion criteria encompassed patients aged 18 years and over, those diagnosed with ICH, and those prescribed at least two drugs during hospitalization, while we did not include patients whose hospitalization lasted less than 7 days, those who were diagnosed with other neurological diseases and patients with incomplete medical files. For each day of hospitalization, the online checker Micromedex® software was used to identify pDDIs and classify them according to severity. A total of 110 participants were analysed. A high prevalence of pDDIs (98.2%) was observed. The median number of pDDIs regardless of severity, was 8.00 (IQR 4.75-13.00;1-30). The pairs of drugs involving cardiovascular medicines were the most commonly identified pDDIs. Twenty percent of the total number of participants was exposed to pCDDIs. The use of multiple drugs from different pharmacological-chemical subgroups and the prescribing of anticoagulant therapy significantly increase the chance of pCDDI (aOR with 95% CI 1.19 (1.05-1.35) and 7.40 (1.13-48.96), respectively). This study indicates a high prevalence of pDDIs and pCDDIs in patients with sICH. The use of anticoagulant therapy appears to be the only modifiable clinically relevant predictor of pCDDIs.

Predictors of hemorrhagic transformation after acute ischemic stroke based on the experts opinion / Preditores de transformação hemorrágica após acidente vascular cerebral isquêmico agudo a partir da opinião de especialistas

ABSTRACT Background: Hemorrhagic transformation (HT) is a common complication after ischemic stroke. It may be associated to poor outcomes. Some predictors of HT have been previously identified, but there remain controversies. Objective: To describe the risk factors for HT more frequently reported by a panel of experts surveyed for this project. Methods: We sent a standard questionnaire by e-mail to specialists in Vascular Neurology from 2014 to 2018. Forty-five specialists were contacted and 20 of them responded to the invitation. Predictors cited by three or more specialists were included in a table and ranked by the frequency in which they appeared. A review of the literature looking for published predictive scores of HT was performed, comparing to the answers received. Results: The 20 responding specialists cited 23 different risk factors for HT. The most frequent factors in the order of citation were the volume of ischemia, previous use of antithrombotic medication, neurological severity, age, hyperglycemia at presentation, hypertension on admission, and cardioembolism. Most variables were also found in previously published predictive scores, but they were reported by the authors with divergences of frequency. Conclusion: Although many studies have evaluated HT in patients with acute ischemic stroke, the published risk factors were neither uniform nor in agreement with those cited by the stroke specialists. These findings may be helpful to build a score that can be tested with the goal of improving the prediction of HT.

RESUMO Introdução: A transformação hemorrágica (TH) é uma complicação comum após a isquemia cerebral e pode estar associada a desfechos desfavoráveis. Alguns fatores de risco para TH têm sido identificados, mas ainda há controvérsias. Objetivo: Descrever os fatores de risco para TH mais frequentemente reportados por um painel de especialistas consultados para esse projeto. Métodos: Enviamos um questionário padronizado por e-mail para 45 especialistas em Neurologia Vascular no período de 2014 a 2018. Vinte dos 45 especialistas responderam ao convite. Preditores citados por três ou mais especialistas foram incluídos em uma tabela e classificados pela frequência em que foram reportados. Uma revisão de literatura foi realizada em busca de escores preditivos de TH publicados anteriormente, comparando-os com as respostas recebidas. Resultados: Os 20 especialistas citaram 23 diferentes fatores de risco para TH. Os fatores mais frequentemente citados foram, pela ordem, volume da isquemia, uso prévio de medicação antitrombótica, gravidade neurológica, idade, hiperglicemia na apresentação, hipertensão na admissão e cardioembolismo. A maioria das variáveis também foi incluída em escores preditivos de TH já publicados, mas sem a mesma frequência e com divergências entre os especialistas consultados. Conclusão: Embora muitos estudos tenham avaliado a TH em pacientes com isquemia cerebral, os fatores de risco já publicados não foram uniformes na concordância com aqueles reportados pelos neurologistas vasculares consultados. Esses achados podem ser úteis para elaborar um escore que possa ser testado para aperfeiçoar a predição de transformação hemorrágica.

Muerte súbita por malformación arteriovenosa cerebral rota: a propósito de un caso / Sudden death due to a broken cerebral arteriovenous malformation: a case report

Resumen:Las malformaciones arteriovenosas (MAV) son comunicaciones anómalas entre arterias y venas sin un lecho capilar intermedio. El nido de la malformación contiene una masa enredada de vasos. Estas malformaciones pueden ser asintomáticas o manifestarse con hemorragias intracerebrales o crisis convulsivas. Las hemorragias suelen estar precedidas por un cefalea intensa de inicio súbito y pueden ser mortales. A continuación se presenta el caso de un masculino de 36 años, sin antecedentes personales patológicos conocidos, que expresó vía telefónica que tenía un "fuerte dolor de cabeza", posteriormente fue encontrado en su casa de habitación por su esposa y el personal de la Cruz Roja en paro cardiorrespiratorio, le realizaron un ciclo de reanimación cardiopulmonar (RCP),presentó ritmo sinusal y fue trasladado al Hospital San Francisco de Asis, donde ingresó sin signos vitales, le realizaron varios ciclos de RCP avanzado, no respondió y se declaró fallecido minutos después.

Abstract:Arteriovenous malformations (AVM) are abnormal communications between arteries and veins without an intervening capillary bed. Malformation nidus contains a tangled mass of vessels. These malformations can be asymptomatic or present with intracerebral hemorrhages or seizures. Bleeding usually preceded by a sudden onset of severe headache and can be fatal. Then the case of a male aged 36 presents with no known medical history, who said by telephone that he had a "headache", was later found in his house by his wife and staff Cruz Red in cardiac arrest, he held a series of cardiopulmonary resuscitation (CPR) presented sinus rhythm and was taken to San Francisco de Asis, where he entered without vital signs Hospital, he performed several cycles of advanced CPR, he did not respond and declared deceased minutes then.

Capsulo-ganglionic bleed: Murder or pathology.

Intra parenchymal (intra cerebral) haemorrhage is the most common type of spontaneous intracranial haemorrhage. It accounts for 10% of all strokes with a 50% case fatality rate. Hypertension is the one of the most common causes of intra parenchymal haemorrhage followed by other causes like, amyloid angiopathies, cocaine abuse, haematologic disorders and head injury. The present case is a case of death due to intra parenchymal haemorrhage where the relatives of the deceased alleged the death to have been caused as a sequel to an assault by neighbours. Autopsy conducted by experts proved that death was due to pathology and not trauma, thereby assisting in establishment of justice. Usually a single deep seated intracranial haemorrhage in ganglionic region without any injury to scalp, skull and brain is due to natural disease. Hypertension is the most common cause of spontaneous intracranial haemorrhage.

Hemorragia cerebral por déficit de factor XIII: a propósito de un caso / Cerebral hemorrhage factor XIII deficiency: a purpose of a case

La estabilidad del coágulo de fibrina es importante desde el punto de vista hemostático. La deficiencia del factor XIII (estabilizador de la fibrina) es un transtorno autosómico recesivo raro con una prevalencia calculada de uno en cinco millones. Se presenta caso de paciente masculino de 26 años de edad quien es portador de este transtorno, quien consulta por cefalea de fuerte intensidad en región hemicraneal derecha acompañado de episodios eméticos, sensación de vértigo sin rigidez de nuca. Es ingresado y realizan estudios imagenológicos RNM (Resonancia Magnética Cerebral con Fase de Angioresonancia) donde se visualiza foco hemorrágico intraparéquimatoso de gran tamaño a nivel de territorio de la cerebral media y otro de menor tamaño a nivel occipital derecha sin la evidencia de malformaciones arteriovenosas. El paciente no tiene buena evolución apareciendo nuevos focos hemorrágicos, el cual fué manejado por equipo multidisciplinario sin requerir acto quirúrgico.

Tracking of Neural Stem Cells in Rats with Intracerebral Hemorrhage by the Use of 3T MRI

OBJECTIVE: To access the feasibility of clinically available 3T MRI to detect the migration of labeled neural stem cells (NSCs) in intracerebral hemorrhage (ICH) in a rat model. MATERIALS AND METHODS: The ethics committee of our institution approved this study. ICH was induced by the injection of collagenase type IV into the right striatum of ten Sprague-Dawley rats. Human NSCs conjugated with Feridex (super-paramagnetic iron oxide: SPIO) were transplanted into the left striatum one week after ICH induction. MRI was performed on a 3T scanner during the first, second, third, fourth, and sixth weeks post-transplantation. MRI was obtained using coronal T2- and T2*-weighted sequences. Two rats were sacrificed every week after in vivo MRI in order to analyze the histological findings. RESULTS: ICH in the right striatum was detected by MRI one and two weeks after transplantation without migration of the NSCs. There was no migration of the NSCs as seen on the histological findings one week after transplantation. The histological findings two weeks after transplantation showed a small number of NSCs along the corpus callosum. On MRI three weeks after transplantation, there was a hypointense line along the corpus callosum and decreased signal intensity in the right periventricular region. Histological findings three weeks after transplantation confirmed the presence of the hypointense line representing SPIO-labeled NSCs. MRI four and six weeks after transplantation showed a hypointense spot in the right periventricular region. The histological findings four and six weeks after transplantation showed the presence of prominent NSCs in the right periventricular region. CONCLUSION: 3T MRI can detect the migration of NSCs in rats with ICH along the corpus callosum. Therefore, 3T MRI could be feasible for detecting the migration of NSCs in the clinical setting of stem cell therapy.

Central nervous system hemorrhage in thrombocytopenic patients: computed tomographic findings in 21 cases

OBJETIVE: To describe the CT scan findings of 21 thrombocytopenic patients with central nervous system (CNS) hemorrhage. METHOD: Retrospective study of the computed tomography (CT) of 21 platelet-depleted patients with CNS hemorrhage. One patient presented two episodes of hemorrhagic episode with different intervals. The clinical data were obtained by the review of the medical records. Two radiologists analyzed the films and reached the decisions by consensus. The following findings were studied: type of bleeding, number of lesions, topography, laterality, size and associated findings. RESULTS: Intraparenchymal hemorrhage (IPH) was the most common findings, found in 20 cases, being six of them associated with subarachnoid and intraventricular hemorrhages. The size of the lesions varied between 1.8 and 10.5 cm. The parietal lobes were more commonly affected (n=11, 50 percent), followed by the temporal (n=7, 31.8 percent), frontal (n=7, 31.8 percent) and occipital (n=2, 9.09 percent) lobes. In 15 cases (68.2 percent) there was a single area of hemorrhage and in the remaining cases there were multiple hemorrhages. Associated findings were found in 20 cases. The most prevalent were edema (n=17, 77.3 percent), hydrocephalus (10, 45.4 percent) and midline shift (n=9, 41 percent). CONCLUSION: The most frequent CT scan findings in thrombocytopenic patients with CNS hemorrhage are single IPH, located mostly in the parietal, temporal and frontal lobes, with varied sizes and associated with edema, hydrocephalus and midline shift.

OBJETIVO: Descrever os achados tomográficos de 21 pacientes trombocitopênicos com hemorragia no sistema nervoso central (SNC). MÉTODO: Estudo retrospectivo das tomografias computadorizadas (TC) de 21 pacientes trombocitopênicos que apresentaram hemorragia no SNC. Um dos pacientes apresentou 2 episódios hemorrágicos em épocas diferentes. Os dados clínicos foram obtidos por revisão de prontuários médicos. Dois radiologistas analisaram os exames e estabeleceram os achados por consenso. Os seguintes achados foram estudados: tipo de sangramento, número de lesões, topografia, lateralidade, tamanho e achados associados. RESULTADOS: A hemorragia intraparenquimatosa foi o achado mais comum, observada em 20 casos, sendo que em seis deles apresentavam hemorragia subaracnóidea e intraventricular associadas. O tamanho das lesões variou entre 1,8 e 10,5 cm (mediana= 4,5 cm). Os lobos parietais foram mais acometidos (n=11, 50 por cento), seguidos pelos temporais (n=7, 31,8 por cento), frontais (n=7, 31,8 por cento) e occipitais (n=2, 9,09 por cento). Em 15 casos (68,2 por cento) houve uma única área de hemorragia, e nos demais múltiplas áreas foram observadas. Em 20 casos foram encontrados achados associados, sendo mais comum edema (n=17, 77,3 por cento), hidrocefalia (n=10, 45,4 por cento) e desvio da linha média (n=9, 41 por cento). CONCLUSÃO: Os achados tomográficos mais freqüentes em pacientes trombocitopênicos com hemorragia cerebral são lesões intraparenquimatosas únicas acometendo principalmente os lobos parietais, temporais e frontais, com tamanhos variados e associadas a edema, hidrocefalia e desvio da linha média.

Perihematoma damage at different time points in experimental intracerebral hemorrhage / 华中科技大学学报（医学）（英德文版）

The damage degree of neurons in perilesion at different time points was observed in order to explore the optimal operation occasion. Piglet lobar hematomas were produced by pressure-controlled infusions of 2.5 mL autonomous blood into the right frontal hemispheric white matter over 15 min, and the metabolic changes were ambulatorily detected with MRS at 3rd, 12th, 24th and 48th h after hematoma induction. Brain tissues of perihematoma were also obtained at different time points. The transcription level of Bax gene was detected by in situ hybridization and apoptosis by TUNEL technique, and the pathologic change of neurons was observed under an electron microscope. The results showed that the number of Bax positive cells reached the peak at 24 h (79.00 +/- 4.243/5 fields). There was no significant difference in A values between 3 h and 6 h, 12 h (P > 0.05), but there significant difference between 24 h and 3 h, 6 h, 12 h (P 0.05). Lac peak mainly occurred at 24 h and 48 h, while on the healthy side, no Lac peak was detectable. The ratio of NAA/Cr presented a descent tendency, but there was no significant difference among the groups before 12 h (P > 0.05), there was very significant difference between 3, 6 and 24, 48 h (P < 0.01). Under electronic microscopy, the neuronal damage surrounding hematoma in 3 to 6 h was milder than in 24 h to 48 h. It was concluded that the secondary apoptosis, damage and metabolic disturbance of the neurons surrounding hematoma was milder in 3-6 h in acute intracerebral hemorrhage, while obviously aggravated in 24-48 h. An effective intervention is needed to reduce secondary damage as soon as possible.

Strangulation injury, a fatal form of child abuse.

Strangulation is a common method of committing murder, though underreported in Indian literature. We managed a girl child, victim of child abuse who later succumbed to its neurological complications. This case report describes the clinical features associated with such injuries and complications which should be anticipated in such cases.

Mortalidad por hemorragias intracerebrales espontáneas: estudio clinicopatológico / Death from spontaneous intracranial hemorrhage: a clinicopathological study

Se realizó un estudio observacional-descriptivo de 75 pacientes fallecidos por hemorragias intracerebrales espontáneas, en el período comprendido entre enero de 1986 y diciembre de 1997, de los cuales 40 (53,34 porciento) pertenecían al sexo masculino y los restantes 35 (46,66 porciento) al femenino, con una edad promedio de 64,35 años. La hipertensión arterial fue el factor de riesgo más encontrado, 33 (44 porciento), seguido por la insuficiencia cardíaca congestiva, 17 (22,67 porciento), mientras que la causa más frecuente estuvo representada por la hemorragia del hipertenso, 40 (53,34 porciento). Los hallazgos anatomopatológicos intracraneales más significativos fueron la hemorragia intraventricular en 26 pacientes (34,67 porciento), el edema cerebral, 24 (32 porciento) y la hemorragia subaracnoidea, 23 (30,67 porciento)(AU)

We carried out an observational and descriptive study of 75 patients who died from spontaneous intracrainial hemorrhages from January 1986 to December 1997, 40 percent of whom (53.34 percent) were males and 35 (46.66 percent) females with and average age of 64.35 years. Blood hypertension was the most prevailing risk factors in 33 patients (44 percent) followed by congestive heart failure in 17 (27.67 percent) whereas the most common cause was represented by hemorrhage in hypertension with 40 patients (53.34 percent). The most significant intracranial anatomopathological findings were intraventricular hemorrhage in 26 patients (34.67 percent), cerebral edema in 24 (32 percent) subarachnoid hemorrhage in 23 cases (30.67 percent)(AU)

Neurotoxoplasmose com apresentaçäo multifocal supurativa e hemorrágica: relato de caso / Neurotoxoplasmosis with multifocal suppurative and hemorrhagic presentation: case report

Neurotoxoplasmose e uma das infeccoes mais comuns em pacientes imunodeprimidos, podendo manifestar-se raramente sob a forma hemorragica. Descrevemos um caso com apresentacao tomografica caracterizada por imagens nodulares multiplas hiperdensas com edema perilesional. A correcao anatomo-patologicademonstrou lesoes focais hemorragicas pela toxoplasmose.

Enfermedad de Moschcowitz (púrpura trombocitopénica trombótica, microangiopatía trombótica cerebral). Informe de cuatro casos / Moschcowitz disease (thrombotic thrombocytopenic purpura, thrombotic cerebral microangiopathy) A report four cases

Se informan cuatro casos de autopsia con enfermedad de Moschcowitz, una niña, un hombre y una mujer jovenes, y una de mediana edad. En todos hubo una evolución corta con somnolencia y pérdida del estado de despierto, dos enfermas presentaron crisis convulsivas, el hombre joven parestesias y alteración de funciones cerebrales superiores y otra enferma focalización con hemiplejia izquierda. En los dos primeros casos se encontraron hemorragias cerebrales pequeñas y en los otros dos casos no hubo datos macroscópicos relevantes. Los hallazgos microscópicos en todos fueron oclusión de vénulas y capilares cerebrales por trombos de fibrina y escaso infiltrado mononuclear perivascular. Esta es una entidad rara y poco entendida que médicos clínicos y patólogos deben conocer y diagnosticar

Acidente vascular de tronco encefálico: estudo de 21 casos / Vascular stroke of the brain steam: study of 21 cases

Através de estudo prospectivo foram acompanhados 21 casos de acidente vascular de tronco encefálico, durante 12 meses, entre 1991 e 1992. O objetivo foi observar a relaçäo entre o tipo de lesäo, a apresentaçäo clínica e a evoluçäo. Com o exame neurológico, a tomografia computadorizada (CT) e, em alguns casos, angiografia e ressonancia magnética (MRI) demonstrou-se a topografia da lesäo. A hemorragia pontomesencefálica foi o achado mais freqüente. A hipertensäo arterial sistêmica estava presente em 67 por cento dos casos e a sexta década de vida foi a mais atingida. Todos os pacientes receberam tratamento clínico visando as doenças associadas. utilizou-se o Glasgow Outcome Scale (GOS) para evoluçäo: 28 por cento tiveram GOS 5, 24 por cento GOS 4,5 por cento GOS 3,28 por cento GOS 2 e 14 por cento GOS 1. Notou-se, por esta experiência, tratar-se de uma patologia grave e com várias formas de apresentaçäo. quando o paciente foi admitido em coma e com lesäo mista, a evoluçäo foi desfavorável (p < 0,01). Muitas vezes foi difícil correlacionar os casos com as descriçöes clássicas da literatura, por isto chamanos a atençäo para o fato de que se deva observar individualmente as características de cada caso

La hemorragia secundaria en el tallo cerebral (de Duret): estudio clínico patológico de 195 casos de autopsia / Secondary brain stem hemorrhage of Duret. A clinicopathologic study of 195 autopsy cases

La hemorragia secundaria en el tallo cerebral es una complicación de cualquier masa supratentorial de crecimiento rápido. Se revisaron los protocolos de 17,422 autopsias efectuadas de 1969 a 1992. Se encontraron 377 casos de masas supratentoriales de crecimiento rápido, en 195 hubo hemorragia secundaria y en 182 no se presentó. Hubo un ligero predominio de estas hemorragias en hombres. Las masas supratentoriales que produjeron hemorragia secundaria fueron, en orden decreciente de frecuencia; hemorragias asociadas a hipertensión arterial, infartos arteriales embólicos, hematomas subdurales, tumores aneurismas saculares rotos, etc. Hubo infarto en el territorio de la arteria cerebral posterior en el 20.5 por ciento, y sólo se encontraron datos clínicos de descerebración en el 11.8 por ciento de los casos. Se revisan algunos conceptos sobre la patogenia y se analizan las posibles explicaciones para la ausencia de hemorragia en muchos casos de lesiones supratentoriales expansivas. Se concluye que el número de casos con esta complicación fatal en este material de autopsias es alarmantemente elevado

Informe de un caso de hemorragia intraventricular espontánea en un recién nacido a término

Se informa de un caso de un recién nacido con hemorragia intraventricular, a quien se le confirmó con estudios neuroradiológicos, hemorragia de los plexos coroides, sin que se pudiera demostrar factores de riesgo asociados a este evento.