Effects of daidzein on rat ovary against ischemia-reperfusion

Purpose: Our aim was to investigate protective effects of daidzein treatment on ischemia-reperfusion (I/R) injury-induced ovarian tissue by immunohistochemical techniques. Methods: Thirty Sprague Dawley female rats were categorized into three groups as sham, I/R group, and I/R+daidzein groups. Bloods were analyzed for malondialdehyde (MDA), glutathione peroxidase (GSH), and myeloperoxidase (MPO), and ovaries were processed for histological tissue protocol. Results: Both MDA and MPO values were increased in I/R group compared to sham and I/R+daidzein groups. GSH content was increased in I/R+daidzein group compared to I/R groups. In I/R group, theca and follicular cells were degenerated with apoptosis and dilatation and congestion, edema. In I/R+daidzein group, daidzein improved pathologies. In the I/R group, Bax expression was positive with follicular cells, granulosa cells and inflammatory cells. In the I/R+daidzein group, positive Bax reaction was observed in the epithelial, antral, and inflammatory cells. In I/R group, Bcl-2 reaction was in germinative epithelial cells, cells of antral follicle. In the I/R+daidzein group, Bcl-2 expression level was reduced after daidzein treatment. Conclusions: After the I/R procedure, ovarian cells and follicles were degenerated with apoptosis and inflammation. After daidzein treatment, Bax and Bcl-2 signal were decreased. It was observed that daidzein stopped the apoptotic process.

CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión / CD38: role in normal cardiac electrophysiology and in arrhythmias due to ischemia and reperfusion

Introducción: CD38 es una glicoproteína transmembrana de 300 aminoácidos y 45 kDa expresada de forma ubicua en el organismo que cumple importantes funciones en el metabolismo del cofactor NAD+ y en la regulación del movimiento del calcio celular. Uno de los productos enzimáticos de CD38 es el adenosín difosfato ribosa cíclico o ADP-ribosil cíclico (ADPRc), que actúa como segundo mensajero sensibilizando la liberación de calcio inducida por calcio (CICR por su sigla en inglés). En las últimas 3 décadas se han hecho esfuerzos en la investigación del papel de esta enzima en el sistema cardiovascular, sin embargo aún resta mucho por saber. Antecedentes: Los primeros estudios sobre el papel de CD38/ADPRc a nivel miocárdico mostraron un efecto potenciador del transitorio del calcio por parte del ADPRc. Además se ha descrito un papel arritmogénico utilizando distintas técnicas tanto en modelos reduccionistas como en organismos de mamíferos in vivo. Entre ellos se encuentran modelos de ratones Knock Out para CD38 (CD38KO). La enzima forma parte de la vía de señalización adrenérgica a través de la producción de ADPRc, y se la ha vinculado también a procesos patológicos relacionados con hipertrofia ventricular e isquemia miocárdica. Por ejemplo, la inhibición de la actividad de CD38 protegería al corazón contra la injuria por isquemia y reperfusión (I-R) in vivo e in vitro, disminuyendo el área de infarto. Nuestro grupo ha estado estudiando el rol de CD38 en la actividad cardíaca. Hemos reportado alteraciones en el manejo del Ca++ en miocitos ventriculares aislados de ratones CD38KO, y, en ratones CD38KO in vivo, menor frecuencia cardíaca (FC), marcada variabilidad de la FC, así como menor incidencia de arritmias ventriculares ante un estímulo suprafisiológico de cafeína/adrenalina. No obstante, no se ha investigado su papel en las arritmias por isquemia y reperfusión (I-R) teniendo en cuenta la conocida sobrecarga celular de calcio en este contexto y sabiendo que es la principal causa de muerte súbita en la población general. Tampoco sabemos cómo contribuye a la electrofisiología miocárdica en condiciones fisiológicas, específicamente a la morfología del potencial de acción miocárdico (PA) o a la morfología del trazado electrocardiográfico (ECG). Objetivo: Analizar el papel de CD38 en la actividad eléctrica miocárdica estudiando desde el PA celular hasta el ECG de superficie y su posible impacto en arritmias ventriculares producidas por isquemia y reperfusión. Estrategia: Para el desarrollo de la tesis trabajé con modelos de ratones salvajes (wild type, WT) y CD38KO tanto in vivo como in vitro. Estudié el corazón aislado y perfundido mediante el sistema Langendorff realizando registro extracelular (EMG) e intracelular (potencial de acción, PA). Realicé una caracterización de la morfología del PA midiendo la duración al 30% (APD30) y al 90% (APD90) de la repolarización. Comparé entre las cepas WT y CD38KO con y sin estimulo adrenérgico y en la cepa WT entre estado control y ante la inhibición de CD38 con 78c, un fármaco inhibidor de la actividad enzimática de CD38. Para comparar el potencial arritmogénico de los corazones de ambas cepas a la injuria provocada por I-R registré la actividad eléctrica espontánea mediante EMG, en condiciones basales, durante isquemia global y reperfusión. En el modelo in vivo analicé el ECG de ratones WT y CD38KO anestesiados y comparé la actividad basal y la respuesta arrítmica ante un modelo de infarto de miocardio por sobrecarga adrenérgica con isoproterenol. Resultados y discusión: Describí por primera vez la morfología del PA en la cepa CD38KO y no fue distinta a la de los ratones salvajes en condiciones basales. Esta falta de diferencias podría deberse a compensaciones fisiológicas que ocurren ante la carencia de la enzima como el aumento en la expresión de la bomba SERCA2a. Por lo contrario, cuando sometí el preparado a un desequilibrio homeostático estimulando con un agonista beta adrenérgico, la APD90 de los corazones CD38KO no disminuyó como la de los WT. En concordancia, la inhibición aguda de CD38 en el PA miocárdico de corazones WT perfundidos con 78c aumentó la APD90 significativamente sin cambios en el APD30. Cuando sometí a los corazones CD38KO aislados a un medio arritmogénico con alto contenido de calcio y bajo en potasio, la FC en estos no aumentó a diferencia de lo que ocurrió marcadamente en los WT. La respuesta arrítmica ante la isquemia global en el corazón aislado no fue menor en la cepa CD38KO a diferencia de lo esperado, mostrando una incidencia de 57 % en los WT y 75 % en los CD38KO (valor p = 0.61). En el modelo in vivo describí por primera vez el trazado electrocardiográfico (DII) de animales carentes de CD38. No hubo diferencias en la FC, intervalo PR, intervalo QT, amplitud de onda S, ni amplitud de onda T. Sin embargo la duración del QRS fue menor, mientras que la amplitud de la onda R fue mayor en los ratones CD38KO, probablemente secundario a una mayor velocidad de conducción. Estas diferencias se perdieron en la etapa aguda de la isquemia por sobrecarga adrenérgica. En la cepa CD38KO como era esperado vi mayor proporción de pausas sinusales, que se hicieron más evidentes ante la injuria por isoproterenol, lo que podría estar evidenciando una mayor refractariedad del CICR por disminución del contenido de calcio reticular. No se demostró la protección ante arritmias generadas por isquemia en la cepa CD38KO ya que el incremento de la carga arrítmica fue similar en ambas cepas. No hubo diferencias significativas en la proporción de ratones afectados ni en la suma total de extrasístoles ventriculares registradas pero la mortalidad que generó la sobrecarga adrenérgica en el grupo WT fue de 1/3 mientras que la totalidad de los ratones CD38KO sobrevivieron. Conclusiones: En esta tesis presento una caracterización electrofisiológica de CD38 desde el PA en corazón entero hasta la manifestación electrocardiográfica de superficie, con una evaluación especial de su papel en arritmias por I-R y desarrollando técnicas innovadoras a nivel nacional. Las principales conclusiones son: CD38: rol en la electrofisiología cardíaca normal y en arritmias por isquemia y reperfusión 12 - CD38 contribuye a la repolarización tardía disminuyendo el APD90. - La ausencia de la enzima evita el aumento de la FC en un medio arritmogénico con sobrecarga de Ca++ . - CD38 contribuye con un enlentecimiento en la velocidad de conducción miocárdica manifiesta en un descenso de la duración y aumento del voltaje del QRS en los corazones de ratones que no expresan CD38La deleción de CD38 genera un aumento marcado de pausas sinusales ante la isquemia. - No hay evidencia de una protección ante arritmias malignas por I-R in vitro mediante la deleción de CD38. - No se vio una contribución de CD38 a arritmias malignas por isquemia in vivo aunque la ausencia de la enzima parece mejorar el perfil de supervivencia.

Forsythiaside B inhibits cerebral ischemia/reperfusion-induced oxidative stress injury in mice via the AMPK/DAF-16/FOXO3 pathway / 南方医科大学学报

OBJECTIVE@#To study the protective effect of forsythiaside B (FB) against cerebral oxidative stress injury induced by cerebral ischemia/reperfusion (I/R) in mice and explore the underlying mechanism.@*METHODS@#Ninety C57BL/6 mice were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) model group, and low-, medium and highdose (10, 20, and 40 mg/kg, respectively) FB groups. The expression levels of MDA, ROS, PCO, 8-OHdG, SOD, GSTα4, CAT and GPx in the brain tissue of the mice were detected using commercial kits, and those of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 were detected with Western blotting. Compound C (CC), an AMPK inhibitor, was used to verify the role of the AMPK pathway in mediating the therapeutic effect of FB. In another 36 C57BL/6 mice randomized into 4 sham-operated group, MCAO model group, FB (40 mg/kg) treatment group, FB+CC (10 mg/kg) treatment group, TTC staining was used to examine the volume of cerebral infarcts, and the levels of ROS and SOD in the brain were detected; the changes in the protein expressions of AMPK, P-AMPK, DAF-16, FOXO3 and P-FOXO3 in the brain tissue were detected using Western blotting.@*RESULTS@#In mice with cerebral IR injury, treatment with FB significantly reduced the levels of ROS, MDA, PCO and 8-OHdG, increased the activities of antioxidant enzymes SOD, GSTα4, CAT and GPx, and enhanced phosphorylation of AMPK and FOXO3 and DAF-16 protein expression in the brain tissue (P < 0.01). Compared with FB treatment alone, the combined treatment with FB and CC significantly reduced phosphorylation of AMPK and FOXO3, lowered expression of DAF-16 and SOD activity, and increased cerebral infarction volume and ROS level in the brain tissue of the mice (P < 0.01).@*CONCLUSION@#FB inhibits oxidative stress injury caused by cerebral I/R in mice possibly by enhancing AMPK phosphorylation, promoting the downstream DAF-16 protein expression and FOXO3 phosphorylation, increasing the expression of antioxidant enzymes, and reducing ROS level in the brain tissue.

Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats / 中国中药杂志

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.

Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Effect of Xiaoxuming Decoction on synaptic plasticity following acute cerebral ischemia-reperfusion in rats / 中国中药杂志

This study aims to explore the effect of Xiaoxuming Decoction on synaptic plasticity in rats with acute cerebral ischemia-reperfusion. A rat model of cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion(MCAO). Rats were randomly assigned into a sham group, a MCAO group, and a Xiaoxuming Decoction(60 g·kg~(-1)·d~(-1)) group. The Longa score was rated to assess the neurological function of rats with cerebral ischemia for 1.5 h and reperfusion for 24 h. The 2,3,5-triphenyltetrazolium chloride(TTC) staining and hematoxylin-eosin(HE) staining were employed to observe the cerebral infarction and the pathological changes of brain tissue after cerebral ischemia, respectively. Transmission electron microscopy was employed to detect the structural changes of neurons and synapses in the ischemic penumbra, and immunofluorescence, Western blot to determine the expression of synaptophysin(SYN), neuronal nuclei(NEUN), and postsynaptic density 95(PSD95) in the ischemic penumbra. The experimental results showed that the modeling increased the Longa score and led to cerebral infarction after 24 h of ischemia-reperfusion. Compared with the model group, Xiaoxuming Decoction intervention significantly decreased the Longa score and reduced the formation of cerebral infarction area. The modeling led to the shrinking and vacuolar changes of nuclei in the brain tissue, disordered cell arrangement, and severe cortical ischemia-reperfusion injury, while the pathological damage in the Xiaoxuming Decoction group was mild. The modeling blurred the synaptic boundaries and broadened the synaptic gap, while such changes were recovered in the Xiaoxuming Decoction group. The modeling decreased the fluorescence intensity of NEUN and SYN, while the intensity in Xiaoxuming Decoction group was significantly higher than that in the model group. The expression of SYN and PSD95 in the ischemic penumbra was down-regulated in the model group, while such down-regulation can be alleviated by Xiaoxuming Decoction. In summary, Xiaoxuming Decoction may improve the synaptic plasticity of ischemic penumbra during acute cerebral ischemia-reperfusion by up-regulating the expression of SYN and PSD95.

Compound Danshen Dripping Pills pretreatment protects the heart from ischemia/reperfusion injury by enhancing autophagic flux

Abstract Compound Danshen Dripping Pills (CDDPs) have been used in clinical treatment to protect the heart from ischemia/reperfusion (IR) injury for many years. However, the underlying mechanism implicated in the protective effects remains to be explored. Here, we determined the effects of CDDPs in Sprague-Dawley rats with the IR model. Cardiac function in vivo was assessed by echocardiography. Transmission electron microscopy, histological and immunohistochemical techniques, Western blotting and recombinant adeno-associated virus 9 transfection were used to illustrate the effects of CDDPs on IR and autophagy. Our results showed that pretreatment with CDDPs decreased the level of serum myocardial enzymes and infarct size in rats after IR. Apoptosis evaluation showed that CDDPs significantly ameliorated the cardiac apoptosis level after IR. Meanwhile, CDDPs pretreatment increased myocardial autophagic flux, with upregulation of LC3B, downregulation of p62, and increased autophagosomes and autolysosomes. Moreover, the autophagic flux inhibitor chloroquine could increase IR injury, while CDDPs could partially reverse the effects. Furthermore, our results showed that the activation of AMPK/mTOR was involved in the cardioprotective effect exerted by CDDPs. Herein, we suggest that CDDPs partially protect the heart from IR injury by enhancing autophagic flux through the activation of AMPK/mTOR.

Consumption of mate Ilex paraguariensis: a folk beverage with antioxidant power against myocardial ischemic injury

The effects of the aqueous extract of Ilex paraguariensis (Ip)and the flavonoid quercetin were tested during the induction of in vivomyocardial ischemia/ reperfusion in Rattus norvegicus. The antioxidant power of the extract and quercetin were chemically determined. The experimental groups were: control, ischemia/reperfusion induction, Iporal treatment, Iporal treatment and ischemia /reperfusion, quercetin oral treatment, and quercetin oral treatment and ischemia/reperfusion. Rats were anesthetized with sodium thiopental and xylazine via intraperitoneal injection and subsequently underwent 15 minutes of ischemia followed by 15 minutes of reperfusion. Ischemia was promoted by tying the left anterior descending coronary artery. Areas of risk and infarction were stained by intravenous Evans blue and triphenyl tetrazolium chloride. Reactive oxygen species (ROS), antioxidant capacity against peroxylradicals, and lipid peroxidation of the myocardium were quantified. A significant reduction in areas of risk and infarction was detected in the ischemic myocardium treated with Ipand quercetin; ROS generation and lipid peroxidation were significantly reduced, and the antioxidant capacity was elevated. Oral administration of Ippromoted antioxidant benefits in the myocardium during ischemia and reperfusion, which reduced infarction. We suggest that Mate (a hot drink made from steeped dried leaves of Ip) consumption is a potential cardioprotective habit of indigenous people from southern South American countries, which must be better understood scientifically and ethnographically.

Protection of intestinal immune barrier against ischemia/reperfusion injury in a swine model using anisodamine hydrobromide

Abstract Intestinal ischemia/reperfusion (I/R) causes barrier impairment and bacterial influx. This study explored the protective effects of anisodamine hydrobromide (AH) on intestinal I/R injury caused by cardiopulmonary resuscitation (CPR) after cardiac arrest (CA). After successful CPR, minipigs were randomly divided into two groups (n = 8): saline and AH (4 mg/kg), and then treated with saline or AH via central venous injection, respectively. The same procedures without ventricular fibrillation initiation were conducted in the Sham group (n = 8). Levels of interferon gamma (IFN-γ) and interleukin 4 (IL-4) were measured at different time points (0, 0.5, 1, 2, 4, and 6 h) in serum and 6 h in gut associated lymphoid tissues (GALTs) after the return of spontaneous circulation (ROSC) to evaluate changes in the proportion of T-helper type 1 (Th1) and T-helper type 2 (Th2). Moreover, the positive culture rates of GALTs were examined to evaluate bacterial translocation. AH treatment markedly alleviated aberrant arterial blood gas and hemodynamics as well as intestinal macroscopic and morphological changes after CPR. Moreover, AH treatment significantly increased IFN-γ and decreased IL-4 in both serum and GALTs. Furthermore, AH treatment dramatically decreased positive bacterial growth in GALTs. AH treatment mitigated immunosuppression caused by intestinal I/R and protected the intestinal immune barrier against bacterial translocation, thereby reducing the risk of secondary intestinal infection

Leptin relieves ischemia/reperfusion induced acute kidney injury through inhibiting apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.

Pin1 aggravates renal injury induced by ischemia and reperfusion in rats via Nrf2/HO-1 mediated endoplasmic reticulum stress

Purpose: To investigate the role of peptidyl-prolyl cis/trans isomerase 1 (Pin1) on renal ischemia-reperfusion (I/R) injury and underlying mechanism. Methods: By establishing the in vitro and in vivo models of renal I/R, the role of Pin1 was explored by using molecular assays. Results: In renal I/R, endogenous Pin1 level was up-regulated in I/R-impaired kidney. Suppression of Pin1 with juglone afforded protection against I/R-mediated kidney dysfunction, and reduced I/R-induced endoplasmic reticulum (ER) stress in vivo. Consistent with the in vivo results, repression of Pin1 with juglone or gene knockdown with si-Pin1 conferred cytoprotection and restricted hypoxia/reoxygenation (H/R)-driven ER stress in HK-2 cells. Simultaneously, further study uncovered that Nrf-2/HO-1 signals was the association between Pin1 and ER stress in response to renal I/R. In addition, Nrf-2/HO-1 signal pathway was inactivated after kidney exposed to I/R, as indicated by the down-regulation of Nrf-2/HO-1 levels. Furthermore, inhibition of Pin1 remarkably rescued the inactivation ofNrf-2/HO-1. Conclusions: Pin1 modulated I/R-mediated kidney injury in ER stress manner dependent on Nrf2-HO-1 pathway in I/R injury.

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.

The role of macrophage polarization and interaction with renal tubular epithelial cells in ischemia-reperfusion induced acute kidney injury / 生理学报

Acute kidney injury (AKI) is a common critical clinical disease characterized by a sharp decline of renal function. Ischemia-reperfusion (IR) is one of the main causes of AKI. The mortality of AKI remains high due to the lack of early diagnosis and cause specific treatment. IR rapidly initiates innate immune responses, activates complement and innate immune cells, releasing a large number of injury-related molecules such as high mobility group box-1 (HMGB1), inflammatory mediators such as caspase-3, and then recruits immune inflammatory cells including M1 macrophages (Mϕ) to the microenvironment of injury, causing apoptosis and necrosis of renal tubular epithelial cells (TECs). Dead cells and associated inflammation further activate the adaptive immune system, which not only aggravates tissue damage, but also initiates M2 Mϕ participated inflammatory clearance, tissue repair and regeneration. Mϕ, professional phagocytes, and TECs, semi-professional phagocytes, can phagocytose around damaged cells including apoptotic Mϕ and TECs, which are key innate immune cells to regulate the outcome of injury, repair or fibrosis. In recent years, it has been found that erythropoietin (EPO) not only binds to the homodimeric receptor (EPOR)2 to induce erythropoiesis, but also binds to the heterodimeric receptor EPOR/βcR, also known as innate repair receptor, which plays renoprotective roles. Properdin is the only positive regulator in the complement activation of alternative pathway. It also can effectively identify and bind to early apoptotic T cells and facilitate phagocytic clearing by Mϕ through a non-complement activation-dependent mechanism. Our previous studies have shown that Mϕ and TECs associated with EPO and its receptors and properdin are involved in IR injury and repair, but the underlying mechanism needs to be further explored. As an important carrier of cell-to-cell signal transmission, exosomes participate in the occurrence and development of a variety of renal diseases. The role of exosomes involved in the interaction between Mϕ and TECs in IR-induced AKI is not fully defined. Based on the available results in the role of Mϕ and TECs in renal IR-induced AKI, this review discussed the role of Mϕ polarization and interaction with TECs in renal IR injury, as well as the participation of EPO and its receptors, properdin and exosomes.

Effect of curcumin on acute chronic kidney disease due to ischemia-reperfusion syndrome / Efecto de la curcumina en la enfermedad renal crónica agravada por el síndrome de isquemia-reperfusión / Efeito da curcumina na doença renal crônica agudizada pela síndrome isquemia-reperfusão

ABSTRACT Objective: To evaluate the effect of curcumin on renal function, hemodynamics, and renal oxidative profile of rats with chronic kidney disease (CKD) subjected to renal ischemia-reperfusion injury (IRI). Methods: Wistar rats, 250-300 g, distributed in four groups: Sham (n = 5), CKD simulation; CKD (n = 5), 5/6 renal ablation for CKD induction; CKD + IRI (n = 5), CKD and renal pedicle clamping for 30 minutes; and CKD + IRI+curcumin (n = 5), CKD + IRI, curcumin administration 30 mg/kg/day, orally, for 10 days. Renal function (inulin clearance, urine flow, plasma creatinine), hemodynamics (blood pressure), and oxidative profile (peroxides, TBARS, and urine nitrate, non-protein soluble thiols in renal tissue) were evaluated. Results: The CKD + IRI + curcumin group showed increased inulin clearance and reduced plasma creatinine, decreased RVR and increased RBF, decreased oxidative metabolites in urine and increased thiols in renal tissue when compared with the CKD + IRI group. Conclusion: The treatment with curcumin preserved renal function and hemodynamics of animals with acute CKD, improving oxidative profile, with reduction of oxidants and preservation of antioxidant reserve.

RESUMEN Objetivo: Evaluar el efecto de la curcumina sobre la función renal, hemodinámica y el perfil oxidativo renal en ratas con enfermedad renal crónica (ERC) sometidas a isquemia-reperfusión renal (I/R). Métodos: Ratas Wistar, entre 250-300 g, divididas en cuatro grupos: Sham (n = 5), simulación de ERC; ERC (n = 5), ablación de 5/6 de los riñones para inducción de ERC; ERC + I/R (n = 5), ERC y pinzamiento del pedículo renal durante 30 minutos; y ERC + I/R + curcumina (n = 5) y ERC + I/R, administración de curcumina 30 mg/kg/día, vía oral, durante 10 días. Se evaluaron la función renal (clearance de inulina, flujo urinario, creatinina plasmática), hemodinámica (presión arterial) y el perfil oxidativo (peróxidos, TBARS y nitrato urinario, tioles solubles no proteicos en tejido renal). Resultados: El grupo ERC + I/R + curcumina tuvo un aumento en el clearance de inulina y disminución de creatinina plasmática, disminución de la RVR y aumento del FSR, disminución de metabolitos oxidativos en orina y aumento de tioles en el tejido renal en comparación con el grupo ERC + I/R. Conclusión: El tratamiento con curcumina preservó la función renal y la hemodinámica de los animales con ERC agravada, promoviendo una mejora en el perfil oxidativo, con reducción de oxidantes y preservación de la reserva antioxidante.

RESUMO Objetivo: Avaliar o efeito da curcumina na função renal, hemodinâmica e perfil oxidativo renal de ratos com doença renal crônica (DRC) submetidos a isquemia-reperfusão renal (I/R). Métodos: Ratos Wistar, 250-300 g, distribuídos em quatro grupos: Sham (n = 5), simulação da DRC; DRC (n = 5), ablação de 5/6 dos rins para indução de DRC; DRC + I/R (n = 5), DRC e clampeamento do pedículo renal por 30 minutos; DRC + I/R + curcumina (n = 5) e DRC + I/R, administração de curcumina 30 mg/kg/dia, via oral, por 10 dias. Foram avaliadas a função renal (clearance de inulina, fluxo urinário, creatinina plasmática), hemodinâmica (pressão arterial) e perfil oxidativo (peróxidos, TBARS e nitrato urinário, tióis solúveis não proteicos no tecido renal). Resultados: O grupo DRC + I/R + curcumina apresentou elevação do clearance de inulina e redução da creatinina plasmática, diminuição da RVR e aumento do FSR, diminuição de metabólitos oxidativos na urina e aumento dos tióis no tecido renal quando comparado ao grupo DRC + I/R. Conclusão: O tratamento com curcumina preservou a função e hemodinâmica renal dos animais com DRC agudizada, promovendo melhora no perfil oxidativo, com redução de oxidantes e preservação de reserva antioxidante.

18ß-glycyrrhetinic acid attenuates global cerebral ischemia/reperfusion-induced cardiac damage in C57BL/J6 mice

Abstract The aim of the present study is to investigate the cardioprotective effects of 18ß-glycyrrhetinic acid (18ß -GA) against oxidative and histological damage caused by global cerebral ischemia/ reperfusion (I/R) in C57BL/J6 mice. All male mice (n:40) were randomly divided into four groups: (1) sham-operated (Sham), (2) I/R, (3) 18ß-GA, and (4) 18ß -GA+I/R. Ischemia was not applied to the sham and 18ß-GA groups. In the I/R group, the bilateral carotid arteries were clipped for 15 min to induce ischemia, and the mice were treated with the vehicle for 10 days. In the 18ß-GA group, the mice were given 18ß-GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the 18ß-GA+I/R group, the ischemic procedure performed to the I/R model was applied to the animals and afterwards they were intraperitoneally (i.p.) treated with 18ß-GA (100 mg/kg) for 10 days. It was found that global cerebral I/R increased TBARS levels and decreased antioxidant parameters. The 18ß-GA treatment decreased the level of TBARS and increased GSH, GPx, CAT, SOD activities. Also, the control group cardiac tissue samples were observed to have a normal histological appearance with the Hematoxylin-Eosin staining method. Histopathological damage was observed in the heart tissue samples belonging to the I/R group. The 18ß-GA treatment ameliorates oxidative and histological injury in the heart tissue after global ischemia reperfusion, and may be a beneficial alternative treatment

Influência da localização geográfica no acesso às terapias de reperfusão e mortalidade de pacientes com IAMcSST em Sergipe: registro VICTIM / Influence of geographical location on access to reperfusion therapies and mortality of patients with STEMI in Sergipe: VICTIM register

Resumo Fundamento A concentração de serviços de alta complexidade em Aracaju/SE pode proporcionar disparidade na qualidade assistencial para os pacientes do SUS com infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMcSST) cujos sintomas se iniciaram em outras regiões de saúde do estado. Objetivo Avaliar disparidades no acesso às terapias de reperfusão e mortalidade em 30 dias, entre pacientes com IAMcSST, usuários do SUS, em cada uma das 7 regiões de saúde em Sergipe. Métodos Foram avaliados 844 pacientes com IAMcSST no período de 2014 a 2018 atendidos pelo único hospital com capacidade de ofertar intervenção coronariana percutânea (ICP) primária para usuários do SUS no estado de Sergipe. Os pacientes foram divididos em 7 grupos de acordo com o local de início dos sintomas e obedecendo a divisão já existente das regiões de saúde do Estado. Para comparação entre grupos, foi considerada diferença significativa quando p < 0,05. Resultados Do total de 844 pacientes vítimas de IAMcSST e transferidos ao hospital com ICP que atende pacientes do SUS, 386 pacientes (45,8%) realizaram angioplastia primária. A taxa média do uso de fibrinolítico foi de 2,6%, não havendo diferenças entre as regiões. O tempo médio total de chegada ao hospital com ICP foi de 21h55' com mediana de 10h22' (6h30' - 22h52'). A mortalidade total em 30 dias foi 12,8%, mas sem diferenças entre as regiões, mesmo quando ajustada para idade e sexo. Conclusões Este estudo revela que os fibrinolíticos são subutilizados em todo o estado e que existe um atraso significativo no acesso ao hospital com ICP, em todas as regiões de saúde de Sergipe.

Abstract Background The concentration of high-complexity services in Aracaju, Sergipe can impose certain disparity in the quality of care for the patients with ST-segment elevation acute myocardial infarction (STEMI) (STEMI) who receive care from Brazil's Unified Health System (SUS, acronym in Portuguese) and whose symptoms started in other health regions of the state. Objective To evaluate disparities in access to reperfusion therapies and 30-day mortality, among patients with STEMI, who were users of SUS, in each of the 7 health regions of Sergipe. Methods A total of 844 patients with STEMI in the period from 2014 to 2018, assisted by the only hospital with the capacity to offer primary percutaneous coronary intervention (PPCI) to SUS users in the state of Sergipe, were evaluated. The patients were divided into 7 groups according to the location at the onset of symptoms, following the existing division of health regions in the state. For comparison between groups, a significant difference was considered when p < 0.05. Results Of the total of 844 patients suffering from STEMI who were transferred to the hospital with PPCI that serves SUS patients, 386 patients (45.8%) underwent primary angioplasty. The mean rate of fibrinolytic use was 2.6%, with no differences between the regions. The mean total time of arrival to the hospital with PPCI was 21 hours and 55 minutes, with a median of 10 hours and 22 minutes (6 hours and 30 minutes to 22 hours and 52 minutes). Total 30-day mortality was 12.8%, but without differences between the regions, even when adjusted for age and sex. Conclusions This study reveals that fibrinolytics are underused throughout the state and that there is a significant delay in access to the hospital with PPCI, in all health regions of Sergipe.

Consequences of COVID-19 pandemic on myocardial infarction reperfusion therapy and prognosis / Consecuencias de la pandemia COVID-19 en la reperfusión y pronóstico del infarto de miocardio

ABSTRACT Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI). Aim: To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort. Material and Methods: A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019. Results: When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36). Conclusions: During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.

Antecedentes: La pandemia COVID-19 afectó el tratamiento oportuno del infarto agudo de miocardio (IAM). Objetivo: Caracterizar el perfil clínico de pacientes con IAM durante la pandemia COVID-19 y compararlos con una cohorte histórica. Pacientes y Métodos: Estudio caso-control de 96 pacientes con IAM transferidos a un hospital de alto volumen de intervención coronaria percutánea (ICP) entre marzo julio de 2020 y una cohorte histórica de 269 pacientes transferidos en el mismo período de 2019 (n = 269). Resultados: Al comparar los pacientes transferidos durante pandemia y la cohorte histórica, los primeros eran más jóvenes (63 ± 12 y 68 ± 12 años respectivamente, p 12 h desde iniciados síntomas de IAM con elevación ST (44,4 y 0% respectivamente, p < 0,01), una mediana de tiempo puerta-guía mayor (4 y 3 horas respectivamente, p < 0,01), un mayor uso de ICP primaria (97 y 71% respectivamente, p < 0,01), mayor frecuencia de shock cardiogénico (19,8 y 4,1% respectivamente, p < 0.01) y complicaciones mecánicas (10,4 y 1,7% respectivamente, p < 0,01). A treinta días, los primeros tuvieron mayor mortalidad general (19,8 y 1,4% respectivamente p < 0.01) y cardiovascular (12,5 y 1,4% respectivamente, p < 0,01). Durante la pandemia, 40% de los pacientes presentó positividad para COVID-19, siendo un factor predictivo de mortalidad general (razón de riesgo 2,90; intervalos de confianza 95% 1,14-7,36). Conclusiones: Durante la pandemia, hubo retrasos en tiempos de consulta y tratamiento y mayor morbimortalidad del IAM. La positividad de COVID-19 se asoció a peor sobrevida general a treinta días.

Accidente cerebrovascular de la arteria basilar: cannabis como factor de riesgo en jóvenes / Cerebrovascular accident of basilar artery: Cannabis as a risk factor in young people / Acidente Vascular Cerebral (AVC) da artéria basilar: cannabis como fator de risco em jovens

Introducción. La arteria basilar se forma de las arterias vertebrales, cursa sobre el puente y se bifurca originando las arterias cerebrales posteriores. Irriga parte del tronco encefálico, cerebelo, tálamo y los lóbulos occipitales y temporales cerebrales. Su obstrucción es rara (1% de los accidentes isquémicos), puede ocurrir en cualquier parte de su trayecto, con cuadro clínico diverso. En jóvenes se añaden otros factores de riesgo distintos a los cardiovasculares, se incluye el consumo de sustancias psicoactivas. El objetivo de este artículo es presentar el caso de un adulto joven, su evolución posterior a la intervención endovascular y la asociación, pasada por alto, al consumo de cannabinoides. Caso clínico. Individuo de 23 años con 14 horas de parálisis facial periférica derecha, diplopía, disartria, hemiparesia e hiperreflexia izquierda, disfagia, náuseas y emesis. Tomografía Axial Computarizada de cráneo simple sin alteraciones. Posteriormente, al realizarse resonancia magnética nuclear, se evidencia isquemia pontomesencefálica y focos isquémicos agudos lacunares en lóbulos cerebelosos. Se consideró comprometido el territorio de la arteria basilar, por lo que se realizó angiotomografía que evidenció una obstrucción crítica de dicho vaso a nivel del tercio distal. Se realizó trombectomía con stent-retriever con recanalización total de la arteria basilar con flujo en toda su extensión. Al egreso fue clasificado como TOAST idiopático. Conclusiones. Las escalas etiológicas para stroke creadas para adultos mayores sobreestiman la etiología idiopática en pacientes jóvenes, lo cual puede ocasionar que el consumo de cannabis sea pasado por alto como causante pese a la asociación reportada por la literatura.

Introduction. The basilar artery is formed from the vertebral arteries, runs over the pons and bifurcates, originating the posterior cerebral arteries. It irrigates part of the brainstem, cerebellum, thalamus, and the occipital and temporal lobes of the brain. Its obstruction is rare (1% of ischemic accidents), it can occur in any part of its path, with a diverse clinical condition. In young people, other risk factors other than cardiovascular ones are added; psychoactive substance use is included. The objective of this article is to present the case of a young adult, his evolution after endovascular intervention and the association, overlooked, to the consumption of cannabinoids. Clinical case. 23-year-old man with 14 hours of right peripheral facial paralysis, diplopia, dysarthria, left hyperreflexia and hemiparesis, dysphagia, nausea and emesis. Simple skull Computerized Axial Tomography without alterations. Subsequently, when a nuclear magnetic resonance was performed, pontomesencephalic ischemia and acute lacunar ischemic foci in the cerebellar lobes were evidenced. The basilar artery territory was considered compromised, so a CT angiography was performed, which revealed a critical obstruction of said artery at the level of the distal third. A stent-retriever thrombectomy was performed with total recanalization of the basilar artery with flow in its entirety. Upon discharge, he was classified as "idiopathic" according to the TOAST classification. Conclusions. The etiological scales for stroke created for older adults overestimate idiopathic etiology in young patients, which may cause cannabis use to be overlooked as a cause despite the association reported in the literature.

Introdução. A artéria basilar é formada pelas artérias vertebrais, passa pela ponte e se bifurca, originando as artérias cerebrais posteriores. Irriga parte do tronco cerebral, cerebelo, tálamo e os lobos occipital e temporal do cérebro. Sua obstrução é rara (1% dos acidentes isquêmicos), podendo ocorrer em qualquer parte de seu trajeto, com quadro clínico diverso. Nos jovens, são adicionados outros fatores de risco além dos cardiovasculares, incluindo o consumo de substâncias psicoativas. O objetivo deste artigo é apresentar o caso de um adulto jovem, sua evolução após a intervenção endovascular e a associação, despercebida, ao consumo de canabinoides. Caso clínico. Indivíduo de 23 anos com 14 horas de paralisia facial periférica direita, diplopia, disartria, hemiparesia e hiperreflexia esquerda, disfagia, náuseas e vômitos. Tomografia axial computadorizada de crânio simples sem alterações. Posteriormente, quando foi realizada a ressonância magnética nuclear, foram evidenciados isquemia pontomesencefálica e focos agudos de isquemia lacunar nos lobos cerebelares. O território da artéria basilar foi considerado comprometido, por isso foi realizada uma angiotomografia, que revelou uma obstrução crítica do referido vaso no terço distal. Foi realizada trombectomia stent-retriever com recanalização total da artéria basilar com fluxo em sua totalidade. No momento da alta, foi classificado como TOAST idiopática. Conclusões.As escalas etiológicas para AVC criadas para idosos superestimam a etiologia idiopática em pacientes jovens, o que pode fazer com que o uso de cannabis seja negligenciado como causa, apesar da associação relatada na literatura.

Effects of dietary creatine supplementation on kidney and striated skeletal muscles of rats submitted to ischemia and reperfusion of hind limbs

ABSTRACT Purpose To evaluate the effect of creatine supplementation in the diet of rats subjected to ischemia and reperfusion of hind limbs. Methods Eighteen male Wistar rats were randomized to receive dietary creatine supplementation (G1) or no supplementation (G2), before being subjected to 4 h of ischemia followed by 4 h of reperfusion. In addition, 10 rats (G3) underwent the same surgical procedure, without ischemia, but with supplementation. After reperfusion, kidney and musculature were evaluated for histological damage and serum levels of alanine aminotransferase, urea and creatinine were obtained. Results The urea dosage showed significant differences between the groups (averages G1 = 155.1; G2 = 211.27; G3 = 160.42). Histological analysis found significant differences between G1 and G2 (but not between G1 and G3) in renal myoglobin cylinders and vacuolar degeneration variables and in hypereosinophilia and karyopyknosis variables in muscle fibers. There were no significant differences in the other variables studied. Conclusions Creatine supplementation was related to fewer histological lesions, as well as lower levels of plasma urea, which may suggest a protective effect against lesions caused by ischemia and reperfusion of posterior paws muscles in Wistar rats.