scholarly journals Potentiation of the protective effect of hypercapnic hypoxia in combination with pharmacological neuroprotective agents

Author(s):  
В.П. Куликов ◽  
Л.А. Каланова ◽  
П.П. Трегуб

Цель исследования - изучение возможности потенцирования нейропротекторного эффекта гиперкапнической гипоксии при помощи комбинации с фармакологическими активаторами основных механизмов, увеличивающих толерантность головного мозга к ишемии/гипоксии. Методика. Исследования проводились на 140 крысах-самцах Wistar, которые подвергались курсам респираторных воздействий гиперкапнической гипоксии (PO2 - 90 мм рт. ст.; PCO2 - 50 мм рт. ст.) в течении 5 сут по 30 мин ежедневно. После завершения курса тренировок крысам вводили фармакологические препараты (активатор аденозиновых рецепторов, блокатор карбоангидразы, активатор опиоидных рецепторов, блокатор ангиотензин-превращающего фермента) и через 24 ч производилась билатеральная окклюзия общих сонных артерий, а через 72 ч производился подсчет поврежденных/уцелевших клеток в СА1 регионе гиппокампа. Результаты. Морфологическая оценка выживаемости нейронов показала, что применение эналаприла усиливало нейропротекторный эффект гиперкапнической гипоксии, применение АТФ и даларгина не показало значимого прироста эффективности, а блокатор карбоангидразы ацетазоламид полностью устранял нейропротекторный эффект респираторных тренировок. Заключение. Выраженным потенцирующим эффектом на нейропротекцию, обусловленную респираторными тренировками с гиперкапнической гипоксией, обладает ее комбинация с ингибитором АПФ (эналаприлом). Aim. We studied the possibility of potentiating the neuroprotective effect of hypercapnic hypoxia using a combination with pharmacological activators of major mechanisms that increase the brain tolerance to ischemia/hypoxia. Methods. Studies were carried out on 140 male Wistar rats conditioned with respiratory hypercapnic hypoxia (PO2 - 90 mm Hg; PCO2 - 50 mm Hg) for 5 days, 30 min daily. After this exposure, the rats were injected with a drug (adenosine receptor activator (ATP), carbonic anhydrase blocker (acetazolamide), opioid receptor activator (dalargin), angiotensin converting enzyme (ACE) blocker (enalapril). 24 hrs later, the common carotid arteries were occluded bilaterally. 72 hrs after drug injection, the damaged/surviving cells in the CA1 region of the hippocampus were counted. Results. Morphological evaluation of neuronal survival showed that enalapril enhanced the neuroprotective effect of hypercapnic hypoxia. ATP and dalargin did not significantly increase this effect, and acetazolamide completely eliminated this neuroprotective effect. Conclusion. Thus, the neuroprotective effect of hypercapnic hypoxia conditioning was potentiated by its combination with an ACE inhibitor.

2021 ◽  
Vol 10 (2) ◽  
pp. 9-22
Author(s):  
D. B. Avdeev ◽  
S. S. Stepanov ◽  
A. V. Gorbunova ◽  
A. Yu. Shoronova ◽  
L. M. Makar'eva ◽  
...  

The aimof research was to study morphofunctional signs of the sensorimotor "dark neurons" formation in the cerebrum of sexually mature white rats under normal conditions and in 40 minutesafter the common carotid arteries (CCA) occlusion.Material and methods.Acute ischemia was simulated in white Wistar rats by a 40-min CCA occlusion. The brain was fixed by immersion and perfusion methods. A comparative morphometric assessment of cyto-and gliocytoarchitectonics of the neocortex was carried out under normal conditions (n = 6), 1 (n = 6), 3 (n= 6), and in 7 days (n = 6) after the common carotid arteries (CCA) occlusion. The Nissl staining, hematoxylin and eosin staining, immunohistochemical typing NSE, MAP-2, HSP-70, p38, CASP3, GFAP and AIF1 were applied. The numerical density of normochromic and hyperchromic (dark) pyramidal neurons, oligodendrocytes, microgliocytes, and the relative area of edema –swelling zones were determined. Statistical hypotheses were tested by nonparametric methods using Statistica 8.0 software.Results.The method of the brain fixation significantly influenced the content of the artifact dark neurons,which are similar in morphology and tinctorial properties to degeneratively altered dark neurons. The appearance of reversibly and irreversibly degeneratively altered dark neurons in the sensorimotor cortex after the CCA occlusion was accompanied by an increase in the relative area of edema  –swelling zones (control  –5.4%, 1st day  –17.6%). The maximum content of degeneratively altered dark neurons (53%) was found in layer V in 7 days after ischemia. According to the findings of immunohistochemical typing NSE, MAP-2, HSP-70, p38, CASP3, the specific proteins of the most degeneratively altered dark neurons were retained, ensuring their restoration and the neural network functioning. The total number density of sensorimotor neurons decreased by 26.4% (p =0.001) in layer III, and by 18.5% in layer V (Mann –Whitney U Test; p = 0.01) in 7 days after the intervention. The revealed changes were of a diffuse focal character. In the zones of degeneratively altered dark neurons accumulation, the content of astrocytes, microgliocytes and oligodendrocytes increased. The neuro-astroglial index (control  –1.62) increased to 2.72 in 3 days after the CCA occlusion. The peak in the number density of microgliocyte s was noted in 1 day, and the oligodendrocytes in 7 days after acute incomplete ischemia (Mann –Whitney U Test; p0.001).Conclusion.After a 40-minute common carotid arteries occlusion, dark neurons were detected in layers III and V of the sensorimotor cortex with underlying hydropic dystrophy; their cytomorphological pro perties indicated the dynamics of their in vivo degenerative changes. Restoration of degeneratively altered dark neurons was accompanied  by  an  increase  in  the  number  of  satellite  oligodendrocytes,  astrocytes  and  microgliocytes. The  revealed changes were considered as one of the variants of reversible changes in neurons in response to moderate ischemic damage.


2019 ◽  
Vol 7 (4) ◽  
pp. 67-74
Author(s):  
S. S. Stepanov ◽  
V. A. Akulinin ◽  
D. B. Avdeev ◽  
A. S. Stepanov ◽  
A. V. Gorbunova

The purposeof the study was devoted to the investigation of nucleoli and related structures of the nucleus of neurons in the brain of white rats in normal and after 20-minute occlusion of the common carotid arteries.Material and methods.Structural types, tinctorial properties, number, shape, size and distribution of neuronal nuclei of the neocortex, hippocampus and amygdala in the control (falsely operated animals, n=5) and after 1, 3, 7, 14 and 30 days (n=25) after acute ischemia were studied by light (stained with hematoxilin and eosin, according to Nisl), electron (uranyl acetate and lead citrate), fluorescence (DAPI) and morphometry.Results. The study showed that neurons with one nucleolus (about 90%) prevailed in the control in all studied parts of the brain. In the postischemic period is marked by considerable heterogeneity of morphological and functional activity of nucleoli – depletion alone, activation and amplification of others. Neocortex, CA1and CA3zones of hippocampus with a large share of neurons (up to 40%) with an increased number of nucleoli were revealed after 1–7 days after ischemia. The highest content of such neurons was observed in the neocortex and CA3field of the hippocampus after 1 and 3 days. 14 days after ischemia, the number of nucleoli in neurons was restored to the level of control and remained so after 30 days.Conclusion. Thus, after acute ischemia caused by 20-minute occlusion of the common carotid arteries, qualitative and quantitative changes in nucleoli were revealed. Within 7 days after reperfusion, there was an "adaptive-reparative shift" in the chromosomal balance and the activity of the existing nucleolar organizers of the preserved neurons increased. These changes we refer to the mechanisms of natural protection of the nervous tissue of the brain in the reperfusion period.


Author(s):  
M. J. Borrelli

It had previously been demonstrated that controlled ultrasonic exposures of the mammalian central nervous system (CNS) produced reversible nerve potential suppression and irreversible limb paralysis. These functional effects appeared immediately after the exposures,but no abnormal morphology was detected with the light microscope for at least 10 min, and not all exposures resulting in functional changes produced observable altered morphology. It was therefore speculated that ultrasound produced its initial effects within the tissue ultrastructure,and that some post-exposure time was required before any changes attained dimensions observable with light microscopy.Ultrasonically exposed CNS tissue has recently been examined with transmission electron microscopy and induced changes have been observed within 30 sec after the exposure. Adult female cats were anesthetized and placed in a stereotaxic unit. The animals were prepared for ultrasonic exposure of the brain as described by W. Fry and the common carotid arteries were cannulated.


1998 ◽  
Vol 118 (4) ◽  
pp. 537-544 ◽  
Author(s):  
Tomoyuki Adachi ◽  
Toshiro Umezaki ◽  
Toshiaki Matsuse ◽  
Takemoto Shin

The larynx has three functions: phonation, airway protection, and respiration. Few studies have dealt with laryngeal respiratory function. To elucidate respiratory regulation by the larynx, we studied the changes in the activity of the intrinsic laryngeal muscles during hypercapnia in decerebrated cats. The electromyographic activities of the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded simultaneously with an electromyogram of the diaphragm, endotracheal pressure, and concentrations of O2 and CO2. The activity of the intrinsic laryngeal muscles during hypercapnia (end-tidal CO2, 8% to 10%) was analyzed in comparison with that during eucapnia. In hypercapnia, both the PCA and TA muscles increased their activities, and the endotracheal pressure during expiration was elevated to a higher level than that in eucapnia. TA muscle activities returned to the level during eucapnia after ligation of the common carotid arteries. These findings suggest that hypercapnia causes a further widening of the glottis during inspiration to decrease inspiratory resistance and a further narrowing of the glottis during expiration to prevent alveolar collapse. Thus it may be concluded that the larynx actively participates in respiratory regulation under the control of the brain stem through a process of peripheral inputs from the carotid receptors.


2022 ◽  
Vol 3 (1) ◽  
pp. 01-07
Author(s):  
Bon Elizaveta I. ◽  
Maksimovich Natalia E. ◽  
Karnyushko Olga A. ◽  
Zimatkin Sergey M ◽  
Lychkovskaya Maria A

Objective. Evaluation of changes in the content of ATP synthase in the parietal cortex and hippocampus of the brain of rats with ischemia of varying severity in a comparative aspect. Methods. The experiments were performed on 88 male outbred white rats weighing 260 ± 20 g. Brain ischemia was modeled under conditions of intravenous thiopental anesthesia (40-50 mg / kg). Total cerebral ischemia was modeled by decapitation of animals. The brain sampling was carried out 1 hour and 24 hours after decapitation - to study tissue respiration of mitochondria, as well as 1 hour later to determine the content of ATP synthase. Subtotal cerebral ischemia was modeled by simultaneous ligation of both common carotid arteries. The material was taken after 1 hour to determine the content of ATP synthase. Stepwise subtotal cerebral ischemia was performed by sequential ligation of both common carotid arteries with an interval of 7 days. The sampling was carried out 1 hour after ligation of the second common carotid artery in each of the subgroups. Partial cerebral ischemia was modeled by ligation of one common carotid artery on the right. The sampling was carried out 1 hour after the operation. Determination of the content of ATP synthase was carried out by immunohistochemical method using monoclonal antibodies. For this purpose, after decapitation, the brain was quickly removed from the rats, pieces of the cerebral cortex were fixed in zinc-ethanol-formaldehyde at + 4 ° C (overnight), then embeddedвinвparaffin. Results. In the group of stepwise subtotal cerebral ischemia, the smallest decrease in the content of ATP synthase was observed in the 1st subgroup with an interval between dressings of 7 days, while the greatest decrease in the content of the enzyme was noted in the 3rd subgroup with the minimum interval between the dressings of the common carotid artery (1 day). Modeling of more severe types of ischemic damage led to pronounced morphological changes in neurons in the parietal cortex and hippocampus of the rat brain - a decrease in their size, deformation of the perikarya, an increase in the degree of neuronal chromatophilia with their simultaneous wrinkling and subsequent death. These disorders were most pronounced in the 3rd subgroup of stepwise subtotal cerebral ischemia with the shortest interval between dressings, which was 1 day, and in the group of total cerebral ischemia. Conclusion. Thus, the most pronounced decrease in the content of ATP synthase was observed in the groups of total cerebral ischemia, subtotal cerebral ischemia and in the 3rd subgroup of stepwise subtotal cerebral ischemia, with a minimal time interval between the ligation of the common carotid artery. In stepwise subtotal cerebral ischemia with an interval between ligation of the common carotid artery of 7 days, the suppression of the ATP synthase content was not so significant.


2018 ◽  
Vol 7 (2) ◽  
pp. 85-89
Author(s):  
A. S. Stepanov ◽  
V. A. Akulinin ◽  
D. B. Avdeev ◽  
A. V. Gorbunova

The aim of the study is to determine functional and proliferative activity of sensorimotor cortex (SMC), hippocampus and amygdala (AM) cells of the brain of white rats in normal and after 20-minute occlusion of the common carotid arteries (without hypotension). Material and methods. Using light microscopy and immunohistochemistry were studied neurons, astrocytes, oligodendroglia and microglia brain normal (n=5) and after 6 h, 1, 3 days (n=15) after acute ischemia. Antibodies to glial fibrillar acid protein (GFAP) and Ki67 (manufacturer: Leica Biosystems Newcastle Ltd, UK) were used. Results. After reperfusion, against the background of neuronal damage (swelling, dystrophic and necrobiotic changes), processes of neuroglia cell proliferation were activated, expression of GFAP (hypertrophy of astrocytes) increased, neuroglial index increased, a large number of satellite astrocytes appeared around large neurons of the SMC. After 3 days in the SMC the content of Ki67-positive cells increased to 18.6% (95% CI: 13.5-24.7%) of all gliocytes, in the hippocampus and AM - respectively - to 7.5% (95% CI: 4.3-12.1%) and 10.7% (95% CI: 6.8-15.9%). Thus, statistically significant differences were revealed between the compared parts of the brain. Conclusion. In the acute period after a 20-minute occlusion of the common carotid arteries in the SMC, the hippocampus and the AM increased functional and proliferative activity of astrocytes, oligodendroglia and microglia, which functioned as a single integrated protective and insulating cellular system with a strong regional specificity.


Author(s):  
William P. Wergin ◽  
Eric F. Erbe

The eye-brain complex allows those of us with normal vision to perceive and evaluate our surroundings in three-dimensions (3-D). The principle factor that makes this possible is parallax - the horizontal displacement of objects that results from the independent views that the left and right eyes detect and simultaneously transmit to the brain for superimposition. The common SEM micrograph is a 2-D representation of a 3-D specimen. Depriving the brain of the 3-D view can lead to erroneous conclusions about the relative sizes, positions and convergence of structures within a specimen. In addition, Walter has suggested that the stereo image contains information equivalent to a two-fold increase in magnification over that found in a 2-D image. Because of these factors, stereo pair analysis should be routinely employed when studying specimens.Imaging complementary faces of a fractured specimen is a second method by which the topography of a specimen can be more accurately evaluated.


Author(s):  
Zafer Sahin ◽  
Alpaslan Ozkurkculer ◽  
Omer Faruk Kalkan ◽  
Ahmet Ozkaya ◽  
Aynur Koc ◽  
...  

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.


Author(s):  
Ann-Sophie Barwich

How much does stimulus input shape perception? The common-sense view is that our perceptions are representations of objects and their features and that the stimulus structures the perceptual object. The problem for this view concerns perceptual biases as responsible for distortions and the subjectivity of perceptual experience. These biases are increasingly studied as constitutive factors of brain processes in recent neuroscience. In neural network models the brain is said to cope with the plethora of sensory information by predicting stimulus regularities on the basis of previous experiences. Drawing on this development, this chapter analyses perceptions as processes. Looking at olfaction as a model system, it argues for the need to abandon a stimulus-centred perspective, where smells are thought of as stable percepts, computationally linked to external objects such as odorous molecules. Perception here is presented as a measure of changing signal ratios in an environment informed by expectancy effects from top-down processes.


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