Predictive significance of pro-inflammatory interleukins at newborns with hypoxic-ischemic encephalopathy

Relevance. Hypoxic-ischemic damage to the central nervous system is accompanied by overproduction of pro-inflammatory interleukins in newborns. Perinatal inflammatory responses contribute to unfavorable outcomes. Methods of investigation. The analysis of the cytokine profile in the blood serum was performed in 45 full-term newborns by the method of enzyme-linked immunosorbent assay within 4–96 hours after birth. 32 children had the signs of HIE stage 2, 13 children — HIE stage 3. Unfavorable neurological consequences were formed in 47,4% of children. Research results. Revealed an increase in the levels of IL1β — 17,7 [13,6; 25,4] and IL6 35,2 [24,9; 45,0] in newborns with HIE. A significant increase in pro-inflammatory cytokines was found in patients with unfavorable outcomes compared with favorable ones. When predicting the disabling consequences of DIE, a high predictive value was established for IL1β and IL6. Conclusion. In newborns with hypoxic-ischemic encephalopathy, an increase in serum IL1β and IL6 is observed. It is advisable to use an increase in IL1β >19,4 pg/ml (OR=12,80; 95% CI: 2,90–56,58) and IL6 >40,1 pg/ml (OR=11,33; 95% CI: 2,46–52,15).

MiRNA-132/212 regulates tight junction stabilization in blood–brain barrier after stroke

MicroRNA-132/212 has been supposed as a critical gene related to the blood–brain barrier (BBB) protection after stroke, but its regulation pathway including the upstream regulator and downstream targets is still unclear. Herein, we demonstrated the cAMP response element-binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) to be the upstream regulator of miRNA-132/212 using CRTC1 knockout and wild-type mice. CRTC1 deletion led to the reduction of miRNA-132/212 expression in mice brain after ischemic stroke, significantly increased infarct volume, and aggravated BBB permeability with worsening neurological deficits. Furthermore, we identified that miRNA-132 repressed Claudin-1, tight junction-associated protein-1 (TJAP-1), and RNA-binding Fox-1 (RBFox-1) by directly binding to their respective 3′-untranslated regions, which alleviated the ischemic damage by enhancing neuronal survival and BBB integrity. Moreover, the co-culture of endothelial cells with CRTC1-deficient neurons aggravated the cell vulnerability to hypoxia, also supporting the idea that miRNA-132/212 cluster is regulated by CRTC1 and acts as a crucial role in the mitigation of ischemic damage. This work is a step forward for understanding the role of miRNA-132/212 in neurovascular interaction and may be helpful for potential gene therapy of ischemic stroke.

Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke

The production of free radicals is inevitably associated with metabolism and other enzymatic processes. Under physiological conditions, however, free radicals are effectively eliminated by numerous antioxidant mechanisms. Oxidative stress occurs due to an imbalance between the production and elimination of free radicals under pathological conditions. Oxidative stress is also associated with ageing. The brain is prone to oxidative damage because of its high metabolic activity and high vulnerability to ischemic damage. Oxidative stress, thus, plays a major role in the pathophysiology of both acute and chronic pathologies in the brain, such as stroke, traumatic brain injury or neurodegenerative diseases. The goal of this article is to summarize the basic concepts of oxidative stress and its significance in brain pathologies, as well as to discuss treatment strategies for dealing with oxidative stress in stroke.

May Argyrophilic Nucleolar Organizer Regions Be Used as a Biomarker for the Detection of the Degree of Ischemic Damage Instead of Tunel in Testicular Torsion?

Background and Objectives: It is of great importance to obtain information about the severity of ischemic damage and duration of testicular torsion for an effective treatment strategy. Nucleolar-organizing regions (NORs) are sites of the ribosomal genes composed of ribosomal DNA and proteins. Post-silver staining NORs are termed “AgNOR”. Since AgNORs clearly reveals the self-renewal potential of cells damaged in ischemic events, we performed the current study. Materials and Methods: The study was carried out in four groups as control, sham, early, and late T/D. In the surgical groups, testes were corrected after a 4-h ischemia period. Testicular tissue samples were taken on the third day after detorsion in group 1, 2, 3, and on the tenth day after detorsion in group 4. TUNEL and silver stainings were applied to all samples. Results: The differences were significant among the groups for both mean AgNOR number and total AgNOR area/total nuclear area (TAA/TNA). Moreover, the differences between control and early torsion-detorsion (T/D), between control and late T/D, between sham and early T/D, between sham and late T/D, and between early T/D and late were statistically significant for AgNOR amount. Furthermore, statistically significant differences among the groups for an average number of apoptotic cells per tubule and the percentage of apoptotic tubule values were detected. Discussion: The apoptotic index gives the ratio of cells that are damaged and will die in a programmed way and cells that remain intact, rather than show the viability of the returning testicle. However, by measuring cells that regenerate with AgNOR, we can show not only those that survive but also cells that can repair themselves. Conclusion: AgNOR proteins are usable for the early observation of ischemic injury levels. The amount of AgNOR protein can enlighten us about the extent of testicular damage after T/D treatment. It may also help the physician in the development of effective treatment strategies for cases.

Bilirubin and cardiovascular risk

This literature review demonstrates the results of experimental and clinical studies, as well as data from meta-analyzes on the effect of bilirubin levels on cardiovascular system. Recent studies provided a new look at the role of bilirubin in cardiovascular disease. Modern concepts consider bilirubin as a powerful endogenous antioxidant with anti-inflammatory effects, capable of influencing the course of atherosclerotic cardiovascular diseases and reducing ischemic damage. The change in bilirubin levels affects the coronary blood flow, the development of collateral circulation and the morphology of coronary plaques. A low bilirubin level is associated with an increase in left ventricular mass and a decrease in its contractility, which, in turn, leads to heart failure and increases the risk of rehospitalizations. Taking into account the above effects of bilirubin, there was interest in assessing the effect of its blood level on the risk of atherosclerotic cardiovascular diseases. Recent studies have attempted to create risk stratification models for adverse cardiovascular events based on bilirubin levels.

THE CARBON MONOXIDE DONOR, TOPIRAMATE, AND BLOCKERS OF AQUAPORINE RECEPTORS DECREASE MYOCARDIAL ISCHEMIA-REPERFUSION INJIRY

We investigated the metabolism of mouse isolated heart under the influence of tricarbonyldichlorothenium (II)- dimer (CORM-2 and 2,3-4,5-bis-O-isopropylidene-βD-fructopyranose sulfamate (topiramate) as potential blockers of aquaporine channel (AQP3) of cardiac myocytes. The results were compared with those obtained from the group receiving anti-AQP3 monoclonal antibodies. A decrease in coronary flow was found during the period preceding ischemia (topiramate did not cause this effect). However, at the end of reperfusion, CORM-2 was responsible for its stabilization. This compound did not affect glucose intake (topiramate increased it only at the end of reperfusion), decreased Ca2+ deposition in cardiac muscle (AQP3-IgG antibodies and topiramate had similar effect), decreased creatinine release, AST (especially at the end of reperfusion). The action of CORM-2 increased the amplitude of the R waveform before ischemia and during reperfusion. At the end of reperfusion the R-wave amplitude decreased. The effect of topiramate caused an increase in amplitude only at the beginning of reperfusion. Administration of CORM-2, topiramate and antibodies resulted in prolongation of the interval before and during ischemia. At the same time, the effect of these drugs and antibodies reduced the development of ischemic damage. The results indicate that the released CO from CORM-2 has effects similar to those of anti-AQP3 antibodies. The action of topiramate had signs of calcium channel blocking.

Study of the Neuroprotective Activity of a New Fumaric Acid Derivative

In a narrowing beam-walking test, on the 21st day after the occlusion of the middle cerebral artery, it was found that the succinic salt of diethylaminoethanol fumaric ester (PDES), at doses of 10 and 75 mg/kg, led to a statistically signifi cant decrease in the severity of sensorimotor defi cit of the anterior and posterior contralateral limbs of male rats under the conditions of cerebral ischemia. The test substance at a dose of 10 mg/kg reduced the volume of ischemic damage to the cerebral cortex of rats by 1.5 times. In terms of neuroprotective activity, the effect of the succinic salt of diethylaminoethanol fumaric ester at a dose of 10 mg/kg is comparable to that of Citicoline at a dose of 500 mg/kg.

659 Four Limb Amputations due to Peripheral Gangrene from Vasopressor Use

Case Symmetrical peripheral gangrene (SPG) is a relatively rare phenomenon characterized by symmetrical distal ischemic damage that leads to gangrene of 2 or more sites in the absence of large blood vessel obstruction, where vasoconstriction rather than thrombosis is implicated as the underlying pathophysiology. We present 2 cases of symmetrical peripheral gangrene (SPG) associated with the use of vasopressors to elevate blood pressure, resulting in four-limb amputation. Both patients had different backgrounds, and each presented to Accident and Emergency (A&E) with Streptococcal septicemia and subsequently septic shock, warranting ICU admission and the use of vasopressors to optimize blood pressure. Both patients then started to develop symmetrical peripheral gangrene of both the upper and lower limbs leading to staged amputations performed electively. Vasopressors including dopamine and norepinephrine are used frequently in the treatment of septic shock and its effectiveness is firmly established. However, it can result in peripheral gangrene due to the prolonged vasoconstrictive effect on peripheral blood vessels. Therefore, it is crucial that the astute physician consider the possibility of the development of peripheral gangrene and amputation when using vasopressors to treat septic shock.