Beata Saniova

Ischemic Tolerance: The Mechanisms of Neuroprotective Strategy

The phenomenon of ischemic tolerance perfectly describes this quote “What does not kill you makes you stronger.” Ischemic pre‐ or postconditioning is actually the strongest known procedure to prevent or reverse neurodegeneration. It works specifically in sensitive vulnerable neuronal populations, which are represented by pyramidal neurons in the hippocampal CA1 region. However, tolerance is effective in other brain cell populations as well. Although, its nomenclature is “ischemic” tolerance, the tolerant phenotype can also be induced by other stimuli that lead to delayed neuronal death (intoxication). Moreover, the recent data have proven that this phenomenon is not limited to application of sublethal stimuli before the lethal stress but reversed arrangement of events, sublethal stress after lethal insult, is rather equally effective. A very important term is called “cross conditioning.” Cross conditioning is the capability of one stressor to induce tolerance against another. So, since pre‐ or post‐conditioners can be used plenty of harmful stimuli, hypo‐ or hyperthermia and some physiological compounds, such as norepinephrine, bradykinin. Delayed neuronal death is the slow development of postischemic neurodegeneration. This allows an opportunity for a great therapeutic window of 2–3 days to reverse the cellular death process. Moreover, it seems that the mechanisms of ischemic tolerance‐delayed postconditioning could be used not only after ischemia but also in some other processes leading to apoptosis. Anat Rec, 292:2002–2012, 2009.

The outcome of patients with severe head injuries treated with amantadine sulphate.

Summary.Objective. To compare our pilot therapeutic results of patients with severe head injury treated either with standard therapy alone or with standard therapy plus amantadine sulphate. Design. Retrospective pilot study. Setting. Intensive Care Unit (ICU), University Hospital. Patients. All patients with severe head injury (GCS < 8) admitted to the ICU between January 1, 1999 and December 31, 2001. The patients were divided into two groups based on the fact, whether they did or did not receive amantadine sulphate included in standard therapy. Group 1 consisted of 41 patients of average age 42.12 ± 16.8 years, of them 35 were males and 6 females. Group 2 included 33 patients of average age 43.91 ± 18.45 years consisting of the 30 males and 3 females. Intervention. Both groups were treated with the standard therapy of severe head injury accepted in our institution. In addition, group 1 patients received amantadine sulphate in a dose of 200 mg i.v. twice daily for 3 days, starting on day 3 of hospitalisation. The reason for amantadin sulphate administration was persistent comatos condition. Measurements and results. Glasgow Coma Scale in patients on admission (after resuscitation) and on discharge from the ICU and mortality rate were compared. In the group 1 the average income GCS was 4.47 ± 2.26 and the average outcome GCS was 9.76 ± 3.95. In the group 2 the average income GCS was 4.70 ± 2.14 and the average outcome GCS was 5.73 ± 3.57. In the amantadine sulphate group two patients out of 33 died (6.06%). There were 17 deaths (51.51%) out of 33 patients in the second control group. Conclusion. In the group of patients with severe brain injuries treated with standard therapy plus amantadine sulphate the outcome GCS was higher and the case fatality rate lower than in the group treated with standard therapy alone.

Biochemical and Clinical Improvement of Cytotoxic State by Amantadine Sulphate

 1. The main idea of the open clinical trial was to compare the income and outcome clinical picture and the evolution of the biochemical markers in the defined intervals in closed head injury group patients.2. In the group of 32 patients, mean age 40.78±15.36 years suffering from closed traumatic brain injury the following markers were measured: glycaemia, malondialdehyde (MDA) as marker of lipid peroxidation, beta-caroten, total SH groups as marker of protein oxidation in the following intervals: between the 1st and the 3rd, between the 3rd and the 7th, between the 1st and the 7th day respectively.3. Glycaemia significantly decreased since the 1st day till the 3rd day (p < 0.05) and since the 1st day till the 7th day (p < 0.05) but it was not significantly changed since the 3rd day till the 7th day (p > 0.05).4. MDA 1st × MDA 3rd p > 0.05 insignificant change, MDA 1st × MDA 7th p < 0.001—high significant decrease, MDA 3rd × MDA 7th—p < 0.0001—very high significant decrease.5. Beta-caroten the 1st × beta-caroten the 3rd day was insignificantly changed—p > 0.05, the 3rd × the 7th day beta-caroten increased significantly—p < 0.0002, the 1st day × 7th day beta-caroten significantly increased—p < 0.0001.6. We examined the SH groups only in nine patients, due to technical problems and SH groups decrease on the 3rd day (p < 0.005).7. In 18 amantadine sulphate subgroups (randomly selected), there was 5.5% lethality and mean outcome GCS (outGCS) 9.83±3.8, while lethality of the control subgroup (n=14) was 42.9%, mean outGCS 6.28±3.5.

The Nose as a Target of Air Pollution, Physiological Aspects and Clinical Relevance of Nasal Trpa1 (Transient Receptor Potential A1) Receptors

The Nose as a Target of Air Pollution, Physiological Aspects and Clinical Relevance of Nasal Trpa1 (Transient Receptor Potential A1) Receptors Worldwide more than several hundred million humans are exposed to severe air pollution, and a significant part of them also smoke. The effect of air pollution on human health has been recognized for many years. The nose, as the first portal of entry to the respiratory system is constantly exposed to a large volumes of air, which is composed of a mixture of gases, particulate matter and infectious agent, and any material other than physiological amount of oxygen, nitrogen, carbon dioxide and water is considered as pollutant. Being exposed to critical amount of air pollutants, nasal cavity shares sophisticated system of protective and defensive mechanisms regarding the lower airways and lungs, however the highest risk of direct exposure to relevant air pollutants is just within the nose. Air pollution is considered to be responsible for some of the pathological processes affecting airways prone to allergic reactions in predisposed subjects, onset of nasal sensorineural hyperresponsiveness, non-specific inflammation, sinonasal cancer and definitely, the risk is not limited just to the nasal mucosa, but can proceed toward the lower airways. The broad spectrum of irritants probably shares very similar molecular background of action. They are capable to activate the cation channenl tranisient receptor potential A1-TRPA1 by covalent modification of the channel protein, because many of them are highly reactive and nonstable molecules with possibilities for various chemical reactions. Activation of this channel is responsible for nociceptive reactions mediated by stimulation of afferent trigeminal nerves, retrograde release of tachykinins, activation of parasympathetic afferent drive leading to increase of mucus output and decrease of nasal patency, with subsequent alteration of nasal functions. Based on the recently described neuro-immune bidirectional relationships, air pollutants may be responsible for recruitment of immune cells with infiltration of the nasal mucosa possibly leading to the inflammatory processes and allergies. Our paper is discussing the nose as the target for air pollution, and focuses on the relevance of TRPA1 channel on trigeminal afferents in pollution mediated responses.

Gamma Coherences in the Default Mode Resting State as a Measure of Consciousness Level

Recent findings indicate that the default mode resting state network (DMRSN) is closely associated with conscious awareness. Thus changes in consciousness level could be reflected in turn in the DMRSN functional state. One of the most important requirements for proper network function is connectivity within the network structural constituents. One of the measures of functional connectivity is analysis of the EEG coherences. In this study we have examined changes in the mean coherences in the gamma spectral band 30–45 Hz in the DMRSN during general anaesthesia (GA) in the open thorax surgery were investigated in twenty patients. They were compared with physiologic EEG findings in twenty alert subjects and the mathematical model of brain death. Results of this study indicate that the decrease in coherences in the physiologic EEG and the patients with one lung ventilation (OLV) groups was roughly proportional to the increasing distance between the electrodes. This created some kind of a structure in the DMRSN. In the OLV group the main finding was a decrease in the coherences in the gamma band. Ten of the anaesthetized subjects showed a clear burst suppression pattern. During this condition the coherences in the pairs connecting the posterior parts of the network decreased. Moreover, the differences between the connections of the anterior to posterior parts of the DMRSN and connections between the posterior parts of the DMRSN were almost lost. However, they showed still highly significant differences in all items when compared with the mathematical model of brain death. In summary the results suggest that the functional connectivity in the DMRSN assessed by mean coherences could be a reliable method for assessing the depth of GA and may be useful for understanding disorders of consciousness in general.

The Enigma of Consciousness – Philosophic and Scientific Approach

Abstract Consciousness is enigmatic beast. It is present with us, comforting, and intuitive core of us. Yet this familiar beast, if we try to touch and describe it, escapes. Questioning and exploring consciousness accompanies mankind since ever. In 20th century we met never before seen states of severe disorders of consciousness – nonresponding people with eyes wide open. Also advancements in general anesthesia made us reexplore this phenomena. Article sums up current philosophic and two most prominent current neuroscientific approaches to what consciousness is and how we can assess it in other human beings. These theories may extend our understanding of ourselves and also help to asses this core quality in our patients in moments, when they do not intelligibly respond or do not respond at all.

Electrical Changes in Deeper Cortical Structures During Balanced General Anesthesia with the Aim on Inhalation Anesthetics Effects

Abstract There are many theories that attempt to explain the mechanisms of the effects of inhalation anesthetics - from simpler, pursuing individual effects of anesthetics on the level of the ion channels, to more complex that are looking for uniform global changes in brain activity common to several agents. However, we still don’t have satisfactory and adequate conclusions. We examined a sample of 39 patients undergoing thoracic surgery at the Clinic of Thoracic Surgery under general anesthesia (GA) and we registered their electroencephalographic (EEG) signals before and during operation. After induction of GA by intravenous (i.v.), we used inhalation anesthetics to maintain GA. We used sevoflurane (SEV) in 20 patients and desflurane (DES) in 19 patients. Then we obtained the EEG data and processed them through mathematical and statistical analysis, to discover any changes of electrical activity in the brain during thoracic surgery under GA. The era of digital recording EEG and present possibilities of modern computer techniques allow quantitative analysis of obtained data. We performed the analysis with the software LORETA (low resolution brain electromagnetic tomography). It is a relatively new research method, which in a similar way as computed tomography (CT) or magnetic resonance imaging (MRI) displays even deeper brain electrical activity, which is hiddeen for a classical EEG approach. We described the general changes in brain electrical activity of the deeper cortical structures within the traditional frequency bands (d, q, a, b and g) during GA at 5 mm spatial resolution. We have shown that the source of the well-known cortical EEG changes after the effect of used inhalation anesthetics is caused by changes situated in the deeper brain structures, particularly the limbic system. Significant changes occurred in the cingulate gyrus for most of an EEG frequency ranges. When comparing the data of patients anesthetised with SEV and DES we found similar changes within the d and q rhythms and then the global changes of EEG activity followed during GA.