Total Cerebral Ischemia Research Articles

LEVELS OF HEAT SHOCK PROTEIN HSP70 IN NEURONS OF PARIETAL CORTEX AND HIPPOCAMPUS IN RATS WITH VARIOUS STAGES OF CEREBRAL ISCHEMIA

The paper examines the issue of increasing the body’s resistance to oxygen deficiency and energy deficit under cerebral ischemia. Adaptation to these changes is represented by an increased number of heat shock proteins in brain neurons. Their expression increases with a decrease of oxygen level in the blood. The aim of the paper is to evaluate HSP70 level in the brain of rats with various stages of cerebral ischemia. Materials and Methods. The study was conducted on 27 white outbred male rats weighing 267±16 g. The authors used such models as partial cerebral ischemia, step-by-step 90 % blood flow shutdown, one-time 90 % blood flow shutdown, and complete cerebral ischemia. Results. In the 1st subgroup of step-by-step 90 % blood flow shutdown (7 days between dressings) there was an increase in the HSP70 level by 25 % in the parietal cortex (p<0.05) compared with the control. However, its concentration in the hippocampus did not change (p>0.05). In the 2nd and 3rd subgroups of step-by-step 90 % blood flow shutdown (3 days and 1 day between dressings), the HSP70 level did not change in any of the studied areas (p>0.05) compared with the control. Compared with the 1st subgroup, in the 2nd subgroup HSP70 level in the parietal cortex was lower by 26 % (p<0.05) and in the hippocampus by 20 % (p<0.05), in the 3rd subgroup it was lower by 30 % (p<0.05) and by 23 % (p<0.05), respectively. No differences in HSP70 levels were found between the 2nd and 3rd subgroups (p>0.05). In the group of one-time 90 % blood flow shutdown, the HSP70 level decreased by 29 % in the parietal cortex (p<0.05) and by 18 % in the hippocampus (p<0.05) compared with the control. In group of one-time 90 % blood flow shutdown, the HSP70 level did not differ from those in the 2nd and 3rd subgroups of step-by-step 90 % blood flow shutdown in the hippocampus. In the parietal cortex, the HSP70 level in the 2nd subgroup was 28 % higher (p<0.05), and in the 3rd subgroup by 23 % higher (p<0.05) compared with the group of one-time 90 % blood flow shutdown. In total cerebral ischemia, the most significant decrease in HSP70 level was observed compared to the control: by 35 % in the parietal cortex (p<0.05) and by 36 % in the hippocampus (p<0.05). Conclusion. Thus, in the 1st subgroup with the maximum interval between dressings, the HSP70 level increased, indicating the activation of compensation mechanisms during hypoxia by protecting proteins from premature proteolytic breakdown and promoting the correct polypeptide folding into a tertiary structure.

Changes in the amino acid pool of cerebral hemispheres in rats with total cerebral ischemia

Objective: assessment of changes in the pool of amino acids (AA) in rats with total cerebral ischemia (TCI). Material and Methods. Experiments were performed on 16 male outbred white rats weighing 260±20 g. TCI was modeled by decapitation of animals. Brain tissue was sampled 1 hour after decapitation. Results. In the parietal lobe (PL) and hippocampus (HC) of TCI group animals 1 hour after their decapitation, we detected an increase in the content of tyrosine (by 43%, p=0.044, and 40%, p=0.044, respectively) and tryptophan (by 24%, p=0.036, and 23%, p=0.046, respectively). Similar trend was observed for methionine that increased by 32% in PL(p=0.046) and by 27% in HC (p=0.046). Analogous increase in the content of L-arginine was noted in PL and HC (by 20%, p=0.037, and 33%, p=0.037, correspondingly). Isoleucine content increased by 12% in PL (p=0.054), while valine content decreased by 15% in HC (p=0.053). The ratio of the combined total content of branched-chain amino acids (BCAA)to the combined content of aromatic AA in TCI significantly declined from 1.4 to 1.0 in PL (p=0.053) and from 1.6 to 1.0 in GC (p=0.053). We observed an increase in methionine content by 33% (p=0.046) in PL and an increase in tryptophan content by 24% (p=0.046) in HC. Conclusion. One-hour TCI caused the following changes in the AA pool: an increase in the content of aromatic AA (tyrosine and tryptophan) and methionine; an increase in the content of L-arginine; and also, an increase in the concentration of the inhibitory neurotransmitter glycine.

Comparative Characteristics of the Ultrastructure of the Pyramidal Neurons of the Parietal Cortex in Cerebral Ischemia of Varying Severity

Introduction: The ultra-structural characteristics of neuron organelles are important indicators of the degree of brain damage during ischemic exposure, which necessitates the study of changes in the ultrastructure of brain neurons. Methods: Models of subtotal, stepwise subtotal, partial and total cerebral ischemia were carried out on 24 outbred white male rats. Electron microscopy methods were used. Results: The data obtained indicate that with total cerebral ischemia the disturbances are more pronounced than with partial cerebral ischemia and stepwise subtotal cerebral ischemia. Conclusion: The data obtained, due to their novelty and relevance; represent a fundamental basis for further studies of neurons in various parts of the brain during cerebral ischemia, with subsequent implementation of the results into clinical practice.

STUDY OF THE EFFECTS OF VINPOCETINE ON INDICATORS OF ACID-ALKALINE STATE FOLLOWING THE ISCHEMIC BRAIN DAMAGE

Vinpocetine is a multipurpose medicine with several pharmacological targets. It is known for its neuroprotective properties. Its mechanism of action in brain pathology is due to a selective inhibitor of phosphodiesterase type 1, inhibition of voltage-gated sodium channels, and a decrease in calcium influx into neurons. Vinpocetine combines high clinical efficacy and safety of use. Therefore it successfully competes in the pharmaceutical market with an ever-increasing number of new medicines. The purpose of the work was to experimentally study the effects of vinpocetine in cats at a dose of 5 mg/kg on the indicators of the acid-base state (ABS) of arterial and venous blood in the simulation of total cerebral ischemia. The effect of vinpocetine on acid-base status indicators should be considered as the most important aspect of its action, contributing to the neuroprotective effect. The paper discusses possible molecular targets and mechanisms for implementing the protective effect of vinpocetine in ischemia, considering its favorable effect on ABS. These new findings may point to increased use of vinpocetine in human cardiovascular diseases accompanied by ABS deterioration.

Post-Morther Changes in Rat Paretial Cortic and Hippocampus Neurons. Morphological Characteristics

Target. Analysis of changes in the morphological characteristics of neurons in such phylogenetically different parts of the rat cerebral cortex in different periods after total cerebral ischemia. Methodology. Experiments were performed on 42 male outbred white rats with an initial weight of 240±20 g. Total cerebral ischemia in outbred white rats was modeled by decapitation. The material was taken at the 1st, 5th, 15th, 30th, and 60th minutes, as well as 5 and 24 hours after decapitation. Results. With total cerebral ischemia, a significant decrease in the size of neurons and deformation of the perikarya were observed. Normochromic neurons completely disappeared at the 60th minute. The number of hyperchromic neurons increased and then progressively decreased. Shriveled neurons accounted for the majority of cells in the studied areas of the cortex at 30-60 minutes, and then, after 5 and 24 hours, cells with pericellular edema predominated in the neuron population. Conclusion. The obtained data on histological changes in neurons of phylogenetically different parts of the cerebral cortex in the dynamics of total cerebral ischemia provide the basis for further detailed study of post-mortem changes in the brain, determining the time of death, creating a fundamental basis for studying the properties of neurons, including their transition from one functional state to other.

Changes In the Course of Energy and Oxidative Processes of The Brain During Its Ischemia

Energy deficiency and oxidative stress are stages of the biochemical cascade in brain damage of ischemic origin. There is information in the literature about their changes in certain types of ischemia, but there are no data on the features and comparative characteristics in cerebral ischemia of varying severity. It was found that the most pronounced disturbances in the prooxidant-oxidant balance and energy metabolism were observed in total cerebral ischemia. Similar, however, less pronounced disorders were found in daily subtotal ischemia and in the subgroup of stepped subtotal ischemia with an interval between ligation of the common carotid arteries of 1 day. The least pronounced disorders were in the subgroup with an interval between ligation of the common carotid arteries 7 days The aim of the work is to assess the state of the energy and oxidative processes of the brain during its ischemia of varying severity.

Содержание нейроглобина в нейронах теменной коры и гиппокампа крыс с церебральной ишемией различной степени тяжести

Introduction. The role of neuroglobin ischemia is still unclear. Some studies indicate its neuroprotective effect due to increased expression of endothelial NOS. Other evidence refutes its significance for neuronal survival under oxygen-deficient conditions, as neuroglobin deficiency appears to increase HIF-1α expression. Materials and methods. The experiments were performed on 56 male outbred white rats weighing 258±18 g. Total cerebral ischemia was simulated by decapitation of animals, whereas the subtotal one was simulated by simultaneous ligation of both carotid arteries. Stepwise subtotal cerebral ischemia was performed by ligating both carotid arteries with an interval of 7 days (subgroup 1), 3 days (subgroup 2), or 1 day (subgroup 3). Results. The study found significant differences in neuroglobin content across three subgroups. In subgroup 1, there was a notable increase in neuroglobin content compared to the control group, with a 13% increase in the parietal cortex (p<0.05) and a 14% increase in the hippocampus (p<0.05). However, subgroup 2 showed a decrease in neuroglobin content, with a 13% decrease in the parietal cortex (p<0.05) and a 7% decrease in the hippocampus (p<0.05). The most significant decrease in neuroglobin content was observed in subgroup 3, with a 31% decrease (p<0.05) in the parietal cortex and a 33% decrease (p<0.05) in the hippocampus. In subgroup 3, the parietal cortex showed a 40% decrease in neuroglobin content compared to subgroup 1 (p<0.05) and a 21% decrease compared to subgroup 2 (p<0.05). Similarly, the hippocampus exhibited a 42.6% decrease in neuroglobin content compared to subgroup 1 (p<0.05) and a 28% decrease compared to subgroup 2 (p<0.05). Conclusion. Thus, the most pronounced disorders of the prooxidant-oxidant balance decreased neuroglobin were observed during a 1-day total cerebral ischemia. Keywords: neuroglobin, ischemia, pyramidal neurons, hippocampus, parietal cortex

Comparative Characteristics of Morphological Changes in Neurons of The Parietal Cortex of Rats with Anoxia of Ischemic and Respiratory Genesis

Acute oxygen deficiency is the basis of a variety of pathological processes in many diseases and environmental factors. When studying the rat brain under conditions of its total ischemia and mechanical asphyxia, the presence of structural changes in both studied periods (after 30 and 60 minutes) was revealed: a decrease in the area and a change in shape (loss of sphericity and an increase in elongation) of cells, as well as a change in the degree of chromatophilia, which was manifested by a decrease in normochromic neurons with a simultaneous increase in hyperchromic shriveled neurons. At the same time, total cerebral ischemia led to more pronounced changes in the studied neurons of the parietal cortex, which was manifested by a more significant decrease in the area of neurons after 30 minutes of anoxia, while shape changes in the form of loss of sphericity and increased elongation were noted to a greater extent with mechanical asphyxia. These differences may be due to the preservation of cardiac activity during mechanical asphyxia for a short time.

DISTURBANCE OF PRO-OXIDANT-ANTIOXIDANT BALANCE IN RATS WITH CEREBRAL ISCHEMIA

Excess of reactive oxygen can lead to membrane damage, accumulation of lipid, protein, and nucleic acid oxidation products, deficiency of reduced pyridine nucleotides and phospholipids of mitochondrial membranes, and then to electrolyte imbalance, mitochondrial swelling, uncoupling of oxidation and phosphorylation processes, and ischemic neuronal death. Thus, the study of oxidative stress and antioxidant system activity is relevant.
 The aim of the study is to examine the changes in the pro-oxidant-antioxidant balance in rats with ischemic brain damage of different degrees of severity (subtotal and total cerebral ischemia).
 Materials and Methods. The experiments were performed on 30 male outbred white rats weighing 260±20 g in compliance with the requirements of the Directive of the European Parliament and the Council of the European Union No. 2010/63/EU of September 22, 2010 on the protection of animals used for scientific purposes.
 Results. A more significant decrease in the content of total SH-groups of proteins and glutathione (by 58 (51; 64) % (p<0.05)), and GSH concentration (by 29 (19; 35) % (p<0.05)) was observed under 24-hour subtotal brain ischemia (SBI) compared with 1-hour SBI. Changes in the glutathione peroxidase activity were multidirectional: in 1-hour SBI, the activity increased by 12 (9; 18) % (p<0.05compared to the control level, and in 24-hour SBI, it decreased by 74 (67; 81) % (p<0.05). In 1-hour SBI, the content of total SH-groups of proteins and glutathione was higher by 60 (54; 65) % (p<0.05), and GSH concentration was higher by 42 (39; 56) % (p<0.05) compared with 1-hour total brain ischemia (TBI). The content of products that react with thiobarbituric acid increased by 59 (51; 63) % (p<0.05). In 24-hout SBI, the content of total SH-groups of proteins and glutathione was higher by 36 (29; 45) % (p<0.05), and GSH concentration was higher by 63 (59; 75) % (p<0.05) compared with 24-hour TBI. The content of products that react with thiobarbituric acid increased by 83 (78; 91) % (p<0.05). The glutathione peroxidase activity in TBI was equal to zero.
 Conclusions. Thus, the most pronounced disturbances in the pro-oxidant-antioxidant balance were observed in 24-hour TBI. Similar, but less pronounced disturbances were observed in 24-hour SBI.

MITOCHONDRIA RESPIRATION IN RAT BRAIN NEURONS UNDER CEREBRAL ISCHEMIA OF VARYING SEVERITY

The knowledge of the mechanisms of energy deficiency development in ischemic lesions is necessary to specify the pathogenesis and assess the damage/compensation ratio.
 The aim of the paper is to study respiration indices of mitochondria of rat brain homogenates in total and subtotal cerebral ischemia.
 Materials and Methods. The experiments were carried out on 88 male outbred white rats weighing 260±20 grams in compliance with the Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes.
 Results. In 1-hour subtotal cerebral ischemia, V2 increased by 24 (18; 27) % (p<0.05), in the presence of malate/glutamate, if compared with the control, while the acceptor control coefficient and the phosphorylation coefficient decreased by 25 (17; 29) % (p<0.05). Other indices (V1, V3, V4, respiratory control coefficient) did not change (p>0.05). In the presence of malate/glutamate under 1-hour SCI, mitochondrial respiration rates V1, V2, V3, and V4 were higher than under 1-hour TCI 89 (82; 93), 58 (55; 63), 24 (21; 29) and 32 (27; 37) % respectively (p<0.05). Decrease in V1, V2, and V3 indices under 24-hour SCI is a consequence of the decrease in oxygen content for mitochondrial respiration. The inhibition of energy processes is more pronounced than under 1-hour SCI, which reflects the extremely low phosphorylation coefficient. Changes in V1, V2, and V3 indices under 1-hour SCI and 1-hour TCI are multidirectional. Their increase under SCI is associated with uncoupling between oxidation and phosphorylation, while their decrease under TCI is associated with a lack of substrates for mitochondrial respiration.
 Conclusion. The most pronounced decrease in respiration indices of the mitochondrial fraction of brain homogenates occurs under total cerebral ischemia due to the complete cessation of neuron blood supply.

Changes in the Content of Neuroglobin in the Neurons of the Cerebral Cortex of Rats with Ischemia

Introduction: Neuroglobin is a metalloprotein of the family globin, which contains protoporphyrin with an iron atom in the center, forming six coordination bonds. Due to its ability to bind oxygen, Ngb enhances the supply of oxygen to the mitochondria of metabolically active neurons. Objectives: To assess the content of neuroglobin in the brain of rats with cerebral ischemia of varying severity. Materials and methods: The experiments were performed on 60 male outbred white rats weighing 260±20 g in compliance with the requirements of the Directive of the European Parliament and of the Council No. 2010/63/EU of September 22, 2010 on the protection of animals used for scientific purposes. Modeling of the cerebral was carried out under conditions of intravenous thiopental anesthesia (40-50 mg/kg). The studies used models of total, subtotal, stepped subtotal, and partial cerebral ischemia. Conclusion: The most pronounced disorders of the prooxidant-oxidant balance, as well as a decrease in the content of neuroglobin, were observed during cerebral ischemia lasting 1 day. During cerebral ischemia with ligation of both common carotid arteries with an interval of 7 days, an increase in the content of neuroglobin was noted, as a manifestation of the activation of compensatory mechanisms.

The content of ATP Synthase in Cerebral Ischemia of Varying Severity Comparative Analysis

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.

Histological disorders of neurons of phylogenetically different parts of the cerebral cortex in partial, subtotal, stepwise subtotal, and total cerebral ischemia

Aim. Measure of the histological changes in neurons in the parietal cortex and hippocampus of rats with partial, subtotal, stepwise subtotal, and total cerebral ischemia. Material and Methods. Studies were performed on 84 rats. Partial cerebral ischemia was modelled by ligation of one common carotid artery. Subtotal cerebral ischemia was modelled by ligation of both common carotid arteries. Stepwise subtotal cerebral ischemia was performed by sequential ligation of both common carotid artery with 7-day, 3-day or 1-day intervals. Total cerebral ischemia (CI) was modelled by decapitation. Results. When comparing the morphological changes of neurons in the parietal cortex and hippocampus, we observed that, with the aggravation of the severity of cerebral ischemia, there was a progressive increase in the number of hyperchromic shrivelled neurons and neurons with pericellular oedema. Modelling of more severe types of ischemic damage lead to pronounced morphological changes in neurons – a decrease in size, deformation of the perikaryon, and increase in the degree of neuronal chromatophilia with their wrinkling. Conclusions. The smallest morphological changes in neurons were noted in the partial cerebral ischemia groups and subgroup 1 of stepwise subtotal cerebral ischemia, with an interval between common carotid artery dressings of 7 days. The most obvious morphological changes were observed in the conditions of total cerebral ischemia after 1 day. Changes in the parietal cortex and hippocampus were unidirectional, but in the parietal cortex, which is most sensitive to oxygen deficiency, they were more pronounced.

Effects of rhodioloside on the neurological functions of rats with total cerebral ischemia/reperfusion and cone neuron injury in the hippocampal CA1 region.

Rhodioloside, the main effective constituent of Rhodiola rosea, demonstrates antiaging and antioxidative stress functions and inhibits calcium overloading in cells. These functions imply that rhodioloside may exert protective effects on hippocampal neurons after total cerebral ischemia/reperfusion injury. In this study, male Wistar rat models of total cerebral ischemia were constructed and randomly divided into four groups: sham-operation, ischemia/reperfusion, low-dosage, and high-dosage groups. The result showed that rhodioloside treatment reduced the apoptosis rates of hippocampal neurons and the histological grades of cone cells in the hippocampal CA1 region, but neuronal density was significantly increased. Besides, the protein expressions of Bcl-2/Bax and p53 were measured and found Bcl-2/Bax was increased and p53 protein level was reduced. Therefore, rhodioloside might have protective effects on rats with ischemia/reperfusion brain injury.

HISTOLOGICAL VIOLATIONS IN THE RAT HIPPOCAMPUS AND PARIETAL CORTEX IN TOTAL CEREBRAL ISCHEMIA

Objective. To analyze the changes in the size and shape of perikaryons and the degree of cytoplasm chromatophilia of the rat hippocampal and parietal cortex neurons at different periods after the modeling of total cerebral ischemia. Material and Methods. The experiments were performed on 42 male outbred white rats with an initial weight of 240 ± 20 g. Total cerebral ischemia in white outbred rats was modeled by decapitation. The material for further histological examination was taken at the 1st, 5th, 15th, 30th and 60th minutes, as well as 5 and 24 hours after decapitation. The study of histological preparations was carried out using an Axioscop 2 plus microscope, a digital video camera and the ImageWarp image analysis program. Among the total number, the cells were isolated by the intensity of cytoplasm staining (chromatophilia). After a preliminary check for the normal distribution of indicators, the data obtained were analyzed by non-parametric statistics. Results. With total cerebral ischemia, a decrease in the size of neurons and deformation of perikaryons were observed. Normochromic neurons completely disappeared at the 60th minute. The number of hyperchromic neurons increased, and then progressively decreased. Shrunken neurons made up the majority of cells in the studied cortical sections at the 30–60th minutes, and then, after 5 and 24 hours, cells with pericellular edema prevailed in the neuron population.Conclusion. The obtained data on histological changes in neurons of phylogenetically different parts of the cerebral cortex in the dynamics of total cerebral ischemia provide the basis for further detailed study of post-mortem changes of the brain as well as determining the time of death, thus creating a fundamental basis for studying the properties of neurons, including their transition from one functional state to another.

The increase in the number of astrocytes in the total cerebral ischemia model in rats

Astrocytes are the most abundant cell class in the CNS. Astrocytic therapies have a huge potential for neuronal repair after stroke. The majority of brain stroke studies address the damage to neurons. Modern studies turn to the usage of morphological and functional changes in astroglial cells after stroke in regenerative medicine. Our study is focused on the changes in the number of astrocytes in the hippocampus (where new glia cells divide) after brain ischemia. Ischemia was modeled by occlusion of tr. brachiocephalicus, a. subclavia sin., a. carotis communis sin. Astrocytes were determined using immunohistochemical labeling with anti GFAP antibody. We found out that the number of astrocytes increased on the 10th and 30th days after stroke in the CA1, CA2 fields, the granular layer of dentate gyrus (GrDG) and hilus. The morphology of astrocytes became reactive in these regions. Therefore, our results revealed long-term reactive astrogliosis in the hippocampus region after total ischemia in rats.

Effect of dexmedetomidine on the changes of EAA and the expression of NMDA NR1 protein in hippocampus in global cerebral ischemia/reperfusion rats

To observe the effects of dexmedetomidine (DEX) on glutamate (Glu), aspartic acid (Asp) release and NMDAR1 expression in hippocampus in global cerebral ischemia/reperfusion rats, and investigate the protective effect and the related mechanism of neurotransmitters. Fifty-four male Wistar rats were randomly divided into three groups (n=18):sham group(A), ischemia/reperfusion group(B), dexmedetomidine pretreatment group(C). Total cerebral ischemia model was set up by four vessel occlusion in rats. Glu and Asp levels were measured with microdialysis at different time. Then the animals were decapitated and the brains were immediately removed to detect NMDAR1 expression in hippocampus area by immunohistochemistry and Western-blot. Compared with that in group B, the levels of Glu, Asp and NMDA NR1 protein were significantly decreased in the dexmedetomidine pretreatment group (P<0.05 or 0.01). Dexmedetomidine might has a protective effect on hippocampus in global cerebral ischemia/reperfusion animals. The protective mechanism might be involved in inhibiting excitatory amino acids(EAA) release and NMDAR1 expression.

Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen‐activated protein kinase signalling pathway

Previous investigations have found that ebselen is able to treat neurodegenerative diseases caused by radical and acute total cerebral ischaemia. The aim of the present study was to investigate the neuroprotective effects of ebselen in a traumatic brain injury (TBI) model. Ninety Sprague-Dawley rats were randomly divided into five groups (n = 18 in each): (i) sham operation; (ii) an injury model group; (iii) low-dose (3 mg/kg) ebselen-treated group; (iv) a moderate-dose (10 mg/kg) ebselen-treated group; and (v) a high-dose (30 mg/kg) ebselen-treated group. The TBI model was created according using a modified weight-drop model. Neurological severity score (NSS), brain water content and histopathological deficits were assessed as parameters of injury severity. Expression of nitric oxide (NO), inducible NO synthase (iNOS) mRNA, Toll-like receptor (TLR) and phosphorylated (p-) p38 mitogen-activated protein kinase (MAPK) were examined by chemical colorimetry, quantitative polymerase chain reaction and western blotting 24 h after intragastric ebselen administration. Rats in the TBI model group exhibited markedly more severe neurological injury (higher NSS, more brain water content and more histopathological deficits) than those in the sham-operated group. Ebselen treatment significantly ameliorated the neurological injury of TBI rats in a dose-dependent manner. Moreover, ebselen significantly reduced the NO and iNOS mRNA levels and inhibited TLR4 and p-p38 MAPK expression, indicating the involvement of NO and p38 MAPK signalling pathways in the neuroprotection afforded by ebselen. In conclusion, ebselen ameliorated neurological injury, possibly by reducing NO levels and modulating the TLR4-mediated p38 MAPK signalling pathway. Therefore, ebselen may have potential to treat secondary injuries of TBI.

Morphological Types of Activated Microglial Cells in the Hippocampus Present after Transient Total Cerebral Ischemia

The aim of the present work was to use immunocytochemical methods (detection of Iba-1 protein) to study the morphological characteristics of hippocampal microgliocytes in rats (n = 15) and describe their cell types in the situation of responses to single episodes of total cerebral ischemia lasting 12 min. The results obtained here provided evidence for the existence of several morphological types of microgliocytes in intact hippocampus and the appearance of new forms in responses to ischemia-induced neuron damage. These changes in the overall hippocampal microgliocyte population were associated with functional activation. During the postischemic period (3, 7, and 14 days), microgliocyte processes were characterized by the appearance of multiple microprocesses, pointing to increased interactions between these and the surrounding cellular elements, which may be an indication of a process eliminating damaged synaptic structures from the neuropil.

Structural Changes in the Choroidoretinal Complex of the Eye in Total Transient Cerebral Ischemia and Their Correction

Electron microscopy and morphometric analysis were used to study structural changes in the choroidoretinal complex of the eye in 40 adult white mongrel male rats in conditions of total transient cerebral ischemia, and the effects of the sterically hindered phenol antioxidant dibornol was evaluated. Total transient cerebral ischemia was found to lead to thrombosis of capillaries in the capillary vascular lamina of the choroid sheath, structural alterations to the hematoretinal barrier, and degeneration of neurons and the radial glia of the retina. Courses of dibornol improved the microcirculation and had protective effects on the neuronal apparatus of the retina, the pigment epithelium, and the radial glia.