Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway / 中华创伤杂志(英文版)

PURPOSE@#Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.@*METHODS@#C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference.@*RESULTS@#Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.@*CONCLUSIONS@#Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction / 中华医学杂志(英文版)

Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.

Baicalin treats cerebral ischemia reperfusion-induced brain edema in rats by inhibiting TRPV4 and AQP4 of astrocytes / 中国中药杂志

This study aims to explore the pharmacodynamic effect of baicalin on rat brain edema induced by cerebral ischemia reperfusion injury and discuss the mechanism from the perspective of inhibiting astrocyte swelling, which is expected to serve as a refe-rence for the treatment of cerebral ischemia with Chinese medicine. To be specific, middle cerebral artery occlusion(suture method) was used to induce cerebral ischemia in rats. Rats were randomized into normal group, model group, high-dose baicalin(20 mg·kg~(-1)) group, and low-dose baicalin(10 mg·kg~(-1)) group. The neurobehavior, brain index, brain water content, and cerebral infarction area of rats were measured 6 h and 24 h after cerebral ischemia. Brain slices were stained with hematoxylin and eosin(HE) for the observation of pathological morphology of cerebral cortex after baicalin treatment. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the content of total L-glutathione(GSH) and glutamic acid(Glu) in brain tissue, Western blot to measure the content of glial fibrillary acidic protein(GFAP), aquaporin-4(AQP4), and transient receptor potential vanilloid type 4(TRPV4), and immunohistochemical staining to observe the expression of GFAP. The low-dose baicalin was used for exploring the mechanism. The experimental results showed that the neurobehavioral scores(6 h and 24 h of cerebral ischemia), brain water content, and cerebral infarction area of the model group were increased, and both high-dose and low-dose baicalin can lower the above three indexes. The content of GSH dropped but the content of Glu raised in brain tissue of rats in the model group. Low-dose baicalin can elevate the content of GSH and lower the content of Glu. According to the immunohistochemical staining result, the model group demonstrated the increase in GFAP expression, and swelling and proliferation of astrocytes, and the low-dose baicalin can significantly improve this situation. The results of Western blot showed that the expression of GFAP, TRPV4, and AQP4 in the cerebral cortex of the model group increased, and the low-dose baicalin reduce their expression. The cerebral cortex of rats in the model group was severely damaged, and the low-dose baicalin can significantly alleviate the damage. The above results indicate that baicalin can effectively relieve the brain edema caused by cerebral ischemia reperfusion injury in rats, possibly by suppressing astrocyte swelling and TRPV4 and AQP4.

Therapeutic Effects of Dimethyl Fumarate on the Rat Model of Brain Ischemia

Abstract Blood-brain barrier (BBB) disruption, inflammation, and cell death are major pathogenic mechanisms in ischemic stroke. Dimethyl fumarate (DMF) has anti-inflammatory and immune-modulatory effects. So, this study aimed to elucidate the effects of DMF on brain ischemia in the middle cerebral artery occlusion (MCAO) model. 69 Sprague-Dawley male rats were allocated into a sham group that was just subjected to surgery stress; vehicle and DMF groups, after MCAO, received vehicle or 30 mg/kg DMF for three days. Neurological scores were evaluated every day. BBB disruption was evaluated by the extravasation of Evans blue. In addition to the measurement of brain water content, the total and infarct volume, numerical density, and the total number of neurons, non-neurons, and dead neurons in the right cortex were estimated by stereological methods. RT-PCR was done to analyze the expression levels of NF-κB and Nrf2. Although brain ischemia treatment with DMF did not have a significant effect on the infarction size, it improved neurobehavioral function, BBB disruption, cerebral edema, increased number of neurons, and expression of Nrf2. It also decreased the number of dead neurons and the expression of NF-κB. DMF beneficial effects on stroke may be mediated through both increase of the Nrf2 and decrease of NF-κB expression

Reflejo de Bezold-Jarish: una puesta al día en neurocirugía / Bezold-Jarisch reflex: an update in neurosurgery

El reflejo de Bezold Jarisch es un reflejo cardioinhibitorio que juega un papel en la homeostasis cardiovascular. Consiste en la triada dada por hipotensión, bradicardia y vasodilatación periférica que puede ser desencadenada tanto por estímulos mecánicos, como químicos. Se considera que el mecanismo eferente contrarresta e inhibe los efectos del influjo simpático y, por el contrario, activa los efectos producidos por el sistema parasimpático. Durante la cirugía neurológica, la disminución de la presión intracraneal posterior a la extracción de colgajo óseo en la craneotomía, el uso de medicamentos osmóticos para disminuir el edema cerebral e incluso la posición del paciente durante el procedimiento suponen situaciones más propensas a la aparición del reflejo.

The Bezold Jarisch reflex is a cardioinhibitory reflex that plays a role in cardiovascular homeostasis. It consists of a triad given by hypotension, bradycardia, and peripheral vasodilation that can be triggered by both mechanical and chemical stimuli. The efferent counteracting mechanism is considered to inhibit the effects of sympathetic influx and, conversely, activates the effects produced by the parasympathetic system. During neurological surgery, the decrease in intracranial pressure after bone flap extraction in the craniotomy, the use of osmotic medications to decrease cerebral edema and even the position of the patient during the procedure supposes situations more prone to reflex appearance

Comparison of half-molar sodium lactate and mannitol to treat brain edema in severe traumatic brain injury: A systematic review / 中华创伤杂志(英文版)

PURPOSE@#Hypertonic fluids such as mannitol and half-molar sodium lactate are given to treat intracranial hypertension in patients with severe traumatic brain injury (TBI). In this study, sodium lactate was compared to mannitol in patients with TBI to investigate the efficacy in reducing intracranial pressure (ICP).@*METHODS@#This study was a systematic review with literature research on articles published in any year in the databases of PubMed, ScienceDirect, Asian Journal of Neurosurgery, and Cochrane Central Register of Controlled Trials. The keywords were "half-molar sodium lactate", "mannitol", "cerebral edema or brain swelling", and "severe traumatic brain injury". The inclusion criteria were (1) studies published in English, (2) randomized control trials or retrospective/prospective studies on TBI patients, and (3) therapies including half-molar sodium lactate and mannitol and (4) sufficient data such as mean difference (MD) and risk ratio (RR). Data analysis was conducted using Review Manager 5.3.@*RESULTS@#From 1499 studies, a total of 8 studies were eligible. Mannitol group reduced ICP of 0.65 times (MD 0.65; p = 0.64) and improved cerebral perfusion pressure of 0.61 times (MD 0.61; p = 0.88), better than the half-molar group of sodium lactate. But the half-molar group of sodium lactate maintained the mean arterial pressure level of 0.86 times, better than the mannitol group (MD 0.86; p = 0.09).@*CONCLUSION@#Half-molar sodium lactate is as effective as mannitol in reducing ICP in the early phase of brain injury, superior over mannitol in an extended period. It is able to prevent intracranial hypertension and give better brain tissue perfusion as well as more stable hemodynamics. Blood osmolarity is a concern as it increases serum sodium.

Síndrome de encefalopatía posterior reversible en el postparto. Estudio de caso / Posterior reversible encephalopathy syndrome in postpartum. Case study

El objetivo del presente ensayo es evaluar el síndrome de encefalopatía posterior reversible en el posparto en una paciente de 22 años, sin antecedentes patológicos personales, antecedentes ginecoobstetricos G(1), C(1), A(0), P(0). Antecedente quirúrgico, cesárea segmentaria de 39 semanas de gestación que es referida por presentar cuadro clínico de 24 horas posteriores a la cesárea segmentaria con dolor abdominal, vómitos y distensión abdominal por lo que es intervenida quirúrgicamente donde realizan re-lapartomias para control de daños. Es ingresada a la Unidad de terapia intensiva con apoyo ventilatorio y sin apoyo vasopresor. Se le realiza Angioresonancia evidenciándose, en secuencia s3DI MC, se identifican las arterias cerebrales anteriores, arterias cerebrales medias, arterias comunicantes posteriores, arteria comunicante anterior y el segmento P1, P2 de la arteria cerebral posterior bilateral con diámetros trayectos conservados. Sin embargo, llama la atención la disminución del diámetro de las arterias corticales de las arterias cerebrales posteriores segmento P3 bilateral. Se concluye que el conocimiento del PRES debe ser extenso y de amplia difusión, de modo que todos los actores relacionados con el cuidado de la salud materna identifiquen de forma precoz y oportuna la condición, reducir la morbimortalidad materna y las secuelas neurológicas a largo plazo(AU)

The objective of this trial is to evaluate the posterior reversible encephalopathy syndrome in the postpartum in a 22-yearold patient, with no personal medical history, G (1), C (1), A (0), P (0). Surgical history, segmental cesarean section of 39 weeks of gestation that is referred for presenting a clinical picture 24 hours after segmental cesarean section with abdominal pain, vomiting and abdominal distension, for which she undergoes surgery where re-lapartomies are performed for damage control. She admitted to the intensive care unit with ventilator support and without vasopressor support. Angioresonance performed, showing, in s3DI MC sequence, the anterior cerebral arteries, middle cerebral arteries, posterior communicating arteries, anterior communicating artery and segment P1, P2 of the bilateral posterior cerebral artery with preserved trajectory diameters identified. However, the reduction in the diameter of the cortical arteries of the bilateral posterior cerebral arteries segment P3 is striking. It concluded that the knowledge of PRES should be extensive and widely disseminated, so that all actors related to maternal health care identify the condition early and in a timely manner, reduce maternal morbidity and mortality and longterm neurological sequelae(AU)

Prevalencia de edema cerebral en pacientes con cetoacidosis diabética / Prevalence of cerebral edema among diabetic ketoacidosis patients

Introducción. El edema cerebral (EC) es la complicación más grave de la cetoacidosis diabética (CAD) en niños. La patogénesis del EC no se conoce con exactitud y su aparición ha sido relacionada con la terapia de rehidratación endovenosa en el tratamiento inicial.Objetivos. Estimar la prevalencia de EC en pacientes con CAD tratados en el Hospital General de Niños Pedro de Elizalde mediante rehidratación endovenosa y analizar potenciales factores de riesgo para el desarrollo de EC.Materiales y método. Estudio de diseño transversal para prevalencia y un análisis exploratorio para comparar las características clínicas y de laboratorio entre los pacientes con y sin EC. Se incluyeron pacientes de 1 a 18 años hospitalizados con diagnóstico de CAD desde el 1 de enero de 2005 hasta el 31 de diciembre de 2014.Resultados. Se analizaron 693 episodios de CAD en 561 historias clínicas. En 10 pacientes, se evidenció EC (el 1,44 %; intervalo de confianza del 95 %: 0,8-2,6). Los pacientes con EC presentaron mayor uremia (p < 0,001), menor presión de dióxido de carbono (p < 0,001) y menor natremia (p < 0,001) que aquellos pacientes sin EC.Conclusión. La prevalencia de EC en pacientes con CAD fue del 1,44 %, menor que la reportada en nuestro país (del 1,8 %). Los factores de riesgo al ingresar asociados a su desarrollo fueron la presencia de uremia elevada, hiponatremia e hipocapnia.

Introduction. Cerebral edema (CE) is the most severe complication of diabetic ketoacidosis (DKA) in children. There is no accurate knowledge of CE pathogenesis and its onset has been related to intravenous rehydration therapy during the initial treatment.Objectives. To estimate the prevalence of CE among DKA patients treated at Hospital General de Niños Pedro de Elizalde with intravenous rehydration and analyze potential risk factors for the development of CE.Materials and methods. Cross-sectional prevalence study and exploratory analysis to compare clinical and laboratory characteristics between patients with and without CE. Patients aged 1-18 years hospitalized with the diagnosis of DKA between January 1st, 2005 and December 31st, 2014 were included.Results. A total of 693 DKA events from 561 medical records were analyzed. Ten patients had evidence of CE (1.44 %; 95 % confidence interval: 0.8-2.6). Patients with CE had higher serum urea levels (p < 0.001), lower carbon dioxide pressure (p < 0.001), and lower serum sodium levels (p < 0.001) than those without CE.Conclusion. The prevalence of CE among DKA patients was 1.44 %, smaller than that reported in our country (1.8 %). The risk factors at admission associated with CE development were high serum urea levels, hyponatremia, and hypocapnia.

Hemorragia subaracnoidea posterior a descompresión Lumbar mínimamente invasiva. Presentación de un caso y revisión de la literatura / Subarachnoid hemorrhage after minimally invasive lumbar decompression. Case report and literature review

Introducción: Las lesiones durales son complicaciones frecuentes en la cirugía de columna. La fuga de liquidocefalorraquideo (LCR) puede originar hemorragia en todos los compartimientos del cerebro. La mayoría ocurre en venas ubicadas en región cerebelosa.Material y método: Se presenta un caso de hemorragia subaracnoidea posterior a una descompresión lumbar mínimamente invasiva asociada a desgarro dural. Resultados: Evoluciona en el postoperatorio con síntomas neurológicos de cefaleas y trastornos del sensorio por lo que se decide evaluarlo con estudios por imágenes vasculares cerebrales identificándose sangrado subaracnoideo.Discusión: El sitio más frecuente de hemorragia intracraneal posterior a una cirugía de columna es el cerebelo. El mecanismo de acción de este tipo de sangrados es desconocido y controversial, hay algunos reportes que sugieren que se trataría de un sangrado venoso. El síntoma más característico de este síndrome es la cefalea. Aunque se desconoce la etiología exacta, se postula que la pérdida de volumen de LCR causa una caída en la presión intracraneal, lo que lleva a un agrandamiento de los senos venosos durales que predisponen al paciente a un hematoma subdural espontáneoConclusión: La fuga de LCR, las alteraciones asociadas al edema cerebral en la hipotensión cerebral podría ser llave del mecanismo que desencadena una hemorragia subaracnoidea.

compartments of the brain. Most occur in veins located in the cerebellar region.Material and method: A case of subarachnoid hemorrhage after a minimally invasive lumbar decompression associated with dural tear is presented.Results: It evolves in the postoperative period with neurological symptoms of headaches and sensory disorders, so it is decided to evaluate it with studies by cerebral vascular images identifying subarachnoid bleeding.Discussion: The most frequent site of intracranial hemorrhage after spinal surgery is the cerebellum. The mechanism of action of this type of bleeding is unknown and controversial, there are some reports that suggest that it would be a venous bleeding. The most characteristic symptom of this syndrome is headache. Although the exact etiology is unknown, it is postulated that the loss of CSF volume causes a drop in intracranial pressure, which leads to an enlargement of the dural venous sinuses that predispose the patient to a spontaneous subdural hematomaConclusion: CSF leakage, alterations associated with cerebral edema in cerebral hypotension could be key to the mechanism that triggers a subarachnoid hemorrhage.

Un ejemplo de respuesta adaptativa integrada: la aclimatación humana a la altitud / An example of integrated adaptive response: human acclimatization to altitude

Se describen las respuestas fisiológicas que el ser humano desarrolla en respuesta a la exposición a la altitud geográfica. Se describen no sólo las alteraciones debidas a una mala coordinación de los ajustes fisiológicos desencadenados durante la aclimatación a la altura sino también sus manifestaciones clínicas más relevantes. Se detallan los mecanismos moleculares subyacentes a tales respuestas y cómo su mejor conocimiento puede permitir aplicar la exposición intermitente a hipoxia como una herramienta útil para la resolución o alivio de determinadas alteraciones y patologías.

We depict the physiological responses developed by the human body in response to the exposure to geographic altitude. The main alterations due to a noncoordinated setup of the physiological adjustments triggered during the acclimatization at altitude are also described, as its most relevant clinical manifestations. The molecular mechanisms underlying such responses are detailed, and how a better knowledge of these processes can allow us to apply intermittent exposure to hypoxia programs as a useful tool for the resolution or relief of certain disorders and pathologies.

Effect of Xingnaojing Injection in treatment of cerebral hemorrhage based on Tabu search algorithm:a real world study / 中国中药杂志

In this study, Tabu search algorithm was used to analyze the effect of Xingnaojing Injection in the treatment of cerebral hemorrhage in the real world. Through the analysis of the results, the therapies based on the pathogeny of cerebral hemorrhage were screened out: Xingnaojing Injection+hemostatic drugs for promoting blood circulation and removing stasis. Cerebral hemorrhage complicated with brain edema: combined with mannitol or mannitol+aescin. The patients with relevant complications in the acute stage of cerebral hemorrhage could select according to the indications: ①Aminocycline+Oxiracetam+Piperacillin Sodium Sulbactam Sodium+Sodium Lactate Ringer; ②Aminocycline+Oxiracetam+Nifedipine+Captopril+Metoclopramide+Cimetidine; ③Insulin+Pantoprazole+So-dium Nitroprusside. The combined therapies for patients of the stable stage with complicating diseases could select according to the indications: ① Monosialotetrahexosyl Ganglioside Sodium+Deproteinized Calf Blood Serum+Nitroglycerin+Compound Potassium Dihydrogn Phosphate; ② Edaravone+Gangliosides+Captopril+Levofloxacin+Tanreqing Injection+Aminophylline. The analysis of subgroup module of drugs for promoting blood circulation and removing blood stasis suggested that the safety of traditional Chinese medicine should be paid attention to in the treatment of cerebral hemorrhage. This study was based on the data of the real world, but with some problems, such as lack of data and confounding factors. The summarized medication plan is only for the reference of clinicians. The clinical application shall be based on the specific situation of patients and the clinical benefits and risks, and pay attention to the incompatibility.

Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 浙江大学学报·医学版

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 南方医科大学学报

OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.

Falla hepática aguda / Acute liver failure

La falla hepática aguda es la pérdida súbita de la función hepática en un corto plazo en un paciente sin enfermedad hepática previa, que se acompaña de coagulopatía y encefalopatía. Es una entidad rara con una incidencia muy baja que afecta especialmente a personas jóvenes. La principal causa en países desarrollados es la toxicidad por acetaminofén, mientras que en los países subdesarrollados son las hepatitis virales. El curso natural de la enfermedad es la progresión rápida a muerte por falla orgánica multisistémica, sepsis o edema cerebral. Después del diagnóstico, los pacientes deben remitirse tempranamente a la unidad de cuidado intensivo y a centros que ofrezcan trasplante hepático. La supervivencia sin trasplante hepático hasta hace pocos años era menor al 15%; sin embargo, en la actualidad puede ser hasta del 50%, dependiendo de la causa, y está relacionada con tratamientos específicos, la disponibilidad de trasplante hepático y una atención óptima en las unidades de cuidados intensivos. El trasplante hepático se constituye en el tratamiento de elección para los pacientes con falla hepática aguda y criterios de mal pronóstico del King's College.

Acute liver failure is the severe short-term liver function impairment in a patient without previous liver disease, which is accompanied by coagulopathy and encephalopathy. It is a rare condition with a very low incidence that affects young people. The leading cause in developed countries is acetaminophen toxicity, while in developing countries is mainly caused by viral hepatitis. The natural course is characterized by a rapid progression to death due to multisystemic organ failure, sepsis, or cerebral edema. After diagnosis, patients must be transferred to the intensive care unit and liver transplantation centers. Survival without liver transplantation until a few years ago was less than 15%; however, currently it can be up to 50% depending on the cause, and it is related to specific treatments, availability of liver transplantation and optimal care in the intensive care units. Liver transplantation is the treatment of choice for patients with acute liver failure and King's College criteria for poor prognosis.

Evaluation of Head Computed Tomography Assessment of Brain Swelling after Acute Traumatic Brain Injury: A Pilot study

Objective To evaluate the interobserver reliability of a new scale created for quantitatively assessing brain swelling in traumatic brain injury (TBI) patients using the computed tomography (CT) findings in three levels. Methods Computed tomography scans of severe head injury patients were randomly selected from a tertiary hospital image database and evaluated by independent groups of neurosurgeons, neurosurgery residents, radiologists, and intensivists from the same hospital. Each specialist assessed the tomographic findings, applying zero to six points in a new scale. The Kappa coefficient was calculated to assess interobserver agreement. Results The highest reliability coefficient was obtained by the neurosurgeons group (0.791; 95% confidence interval [CI]: 0.975­0.607; p < 0.001), followed by the neurosurgery residents group (0.402; 95%CI: 0.569­0.236; p < 0.001) and by the radiologists group (0.301; 95%CI: 0.488­0.113; p < 0.002). The lowest coefficient was found among the intensivists (0.248; 95%CI: 0.415­0.081; p » 0.004). Conclusion The proposed scale showed good reliability among neurosurgeons, and moderate overall reliability. This tomographic classification might be useful to better assist severe TBI victims, allowing to identify the worsening or amelioration of brain swelling, which should be further investigated. The scale seems to be feasible, even in low income countries,where the costof intracranial pressure (ICP)monitoring is higher than thatofCTs.

Reversible vasoconstriction syndrome Study and management proposal / Síndrome de vasoconstricción reversible Propuesta de estudio y manejo

Abstract Reversible vasoconstriction syndrome is a group of clinical-radiological alterations that are characterized by severe sudden-onset headaches and reversible multifocal narrowing of the cerebral arteries. Most patients do not present with focal neurological deficit, although it can be seen in a small group, associated with cerebral edema, stroke or seizures. It is considered to be a benign process that causes disability and death in a minority of patients. The term 'reversible vasoconstriction syndrome' has been proposed to unify a variety of clinical syndromes which are similar, but have different etiologies, and have originated various eponyms. The apparently low frequency of reversible vasoconstriction syndrome and the way it presents make it a diagnostic challenge in the emergency room, and it may go unnoticed without an adequate medical history. A case probably related to the use of isometeptene is presented. (Acta Med Colomb 2019; 44. DOI: https://doi.org/10.36104/amc.2019.1213)

Resumen El síndrome de vasoconstricción reversible es un grupo de alteraciones clínico-radiológicas que se caracterizan por cefaleas intensas de inicio brusco y estrechamiento multifocal reversible de las arterias cerebrales. La mayoría de los pacientes no presentan déficit neurológico focal, aunque puede verse en un grupo reducido asociándose con edema cerebral, ataque cerebrovascular o convulsiones. Es considerado un proceso benigno, en pocos casos originan discapacidad y muerte en una minoría de pacientes. El término de síndrome de vasoconstricción reversible se ha propuesto para unificar a una variedad de síndromes clínicos similares, pero de etiología diferentes y han originados diversos epónimos. La aparente baja frecuencia del síndrome de vasoconstricción reversible y su forma de presentación hace que se convierta en un reto diagnóstico en los servicios de urgencias y puede pasar desapercibido si no se tiene una historia clínica adecuada. Presentamos un caso probablemente relacionado al uso de isometepteno. (Acta Med Colomb 2019; 44. DOI:https://doi.org/10.36104/amc.2019.1213)

Craniectomía descompresiva, una alternativa de tratamiento. Caso clínico / Decompressive craniectomy, an alternative treatment. Clinical case

Introducción: El Trauma Cráneo Encefálico Grave (TCE), continúa siendo un problema de preocupación para las autoridades sanitarias a nivel mundial. A pesar de las diferentes publicaciones existen divergencias en la toma de desición en aplicar la Craniectomía descompresiva (Cd). En el presente trabajo se describe caso clínico portador de Hematoma Epidural (HE), Hipertensión Endocraneana (HE), intervenido quirúrgicamente donde la información fue tomada de la historia clínica realizada en la Unidad de Cuidados Intensivos del Hospital Andino del Chimborazo, Riobamba, Ecuador, previa obtención del consentimiento informado. Presentación del caso: Paciente femenina de 18 años de edad que sufre Trauma craneoencefálico grave, hematoma epidural con efecto de masa y edema cerebral. Sometida a craniectomía descompresiva y tratamiento neurointensivo. Estadía en Unidad de Cuidados Intensivos de seis días, evolución favorable, ausencia de secuelas neurológicas. Conclusiones: La Craniectomía descompresiva mejora la Hipertensión endocraneana, disminuye la estadía UCI, y los días de ventilación mecánica, sin embargo los estudios actuales demuestran que esta intervención no mejora resultados finales. La Craniectomía Descompresiva primaria, en centros de escasos recursos de neuromonitoreo, puede constituir un proceder salvador. La craniectomía descompresiva está indicada en la segunda línea de tratamiento según la American Association of Neurological Surgeons.

Introduction: Serious Skull Trauma (SST), continues to be a problem of concern for health authorities worldwide. Despite the different publications there are divergences in the decision making in applying decompressive craniectomy (dc). In the present work, a clinical case of Epidural Hematoma (EH), Endocranial Hypertension (EH), surgically intervened was described, where the information was taken from the clinical history carried out in the Intensive Care Unit of the Andino del Chimborazo Hospital, Riobamba, Ecuador, after obtaining the informed consent. Presentation of the case: An 18-year-old female patient suffering from severe head trauma, epidural hematoma with mass effect and cerebral edema. Subjected to decompressive craniectomy and neurointensive treatment. Stay in the Intensive Care Unit for six days, favorable evolution, absence of neurological sequelae. Conclusions: Decompressive craniectomy improves intracranial hypertension, decreases ICU stay, and days of mechanical ventilation, however current studies show that this intervention does not improve final results. Primary Decompressive Craniectomy, in centers with scarce resources of neuromonitoring, can be a saving procedure. Decompressive craniectomy is indicated in the second line of treatment according to the American Association of Neurological Surgeons.

Renal replacement therapy in neonates with an inborn error of metabolism / 소아과

Hyperammonemia can be caused by several genetic inborn errors of metabolism including urea cycle defects, organic acidemias, fatty acid oxidation defects, and certain disorders of amino acid metabolism. High levels of ammonia are extremely neurotoxic, leading to astrocyte swelling, brain edema, coma, severe disability, and even death. Thus, emergency treatment for hyperammonemia must be initiated before a precise diagnosis is established. In neonates with hyperammonemia caused by an inborn error of metabolism, a few studies have suggested that peritoneal dialysis, intermittent hemodialysis, and continuous renal replacement therapy (RRT) are effective modalities for decreasing the plasma level of ammonia. In this review, we discuss the current literature related to the use of RRT for treating neonates with hyperammonemia caused by an inborn error of metabolism, including optimal prescriptions, prognosis, and outcomes. We also review the literature on new technologies and instrumentation for RRT in neonates

Primary neurocritical care involving therapeutic hypothermia for acute ischemic stroke patients with malignant infarct cores

BACKGROUND: Acute ischemic stroke patients with malignant infarct cores were primarily treated with neurocritical care based on reperfusion and hypothermia. We evaluated the predictors for malignant progression and functional outcomes. METHODS: From January 2010 to March 2015 ischemic stroke patients with large vessel occlusion of the anterior circulation with infarct volume >82 mL on baseline diffusion weighted image (DWI) within 6 hours from onset, with National Institutes of Health Stroke Scale ≥15 were included. All patients were managed with intent for reperfusion and neurocritical care. Malignant progression was defined as clinical signs of progressive herniation. Predictive factors for malignant progression and outcomes of decompressive hemicraniectomy (DHC) were evaluated. RESULTS: In total, 49 patients were included in the study. Among them, 33 (67.3%) could be managed with neurocritical care and malignant progression was observed in the remainder. Decompressive surgery was performed in nine patients (18.4%). Factors predictive of malignant progression were initial DWI volumes (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.046) and parenchymal hematoma (OR, 6.77; 95% CI, 1.50 to 30.53; P=0.013) on computed tomography taken at Day 1. Infarct volume of >210 mL predicted malignant progression with 56.3% sensitivity and 90.9% specificity. Among the malignant progressors, 77.7% resulted in grave outcomes even with DHC, while all patients who declined surgery died. CONCLUSION: Acute ischemic stroke patients with malignant cores between 82 to 209 mL can be primarily treated with neurocritical care based on reperfusion and hypothermia with feasible results. In patients undergoing surgical decompression due to malignant progression, the functional outcomes were not satisfactory.