Structural aspects of the functional activity of the cerebral cortex synapses in the early postresuscitation period

The numeral density of the revealed with the help of PTA-plane and twisted asymmetric and symmetric interneuronal contacts of the sensomotor brain cortex of rats after 6 minutes mechanical asphyxia has been studied. It was revealed that in 90 minutes and 6 hours the relative contacts of the concave synapses will be increased progressively. This reaction has the compensatory-adaptive character and ensures the restoration of the integrative activity of the brain during the early postresuscitation period.     

Ultrastructure of the cerebral cortex of the cat in the early recovery period after short-term anoxia

The ultrastructure of cat sensomotor cortex has been studied during a 15-minute recovery after 2.5-6-minute oxygen supply cessation. An increase of osmopholia of free and endoplasmic reticulum bound ribosomes was detected in addition to a great number of altered mitochondria with longitudinal crystal arrangement. Besides, numerous activated synapses, local destructive changes of membrane complexes in dendrite and myelinated axons cytoplasm and glycogen granule accumulation in neuroglia were noticed. During the recovery period more prominent changes were shown after a 6-minute anoxia than after a 2.5-minute one.     

Para-membrane neurofilament structures of cerebral cortex synapses during ischemia and in the early postischemic period

Using PTA-method, the structure of para-membrane neurofilament density of interneuronal synapses and PTA-positive contacts in neocortical molecular layer were studied in rats during ischemia and postischemic period. Marked reduction of definite contacts (by 25.4%) was recorded by min 90 of ischemia. However, reorganization of asymmetric contacts started during ischemia and continued in postischemic period. Changes in neurofilament density of synapses (primarily, dense projections of presynaptic grid) underlie the early reorganization of synapse architectonics.     

Phospholipid and malondialdehyde content in the cerebral cortex of rats with incomplete ischemia and in the postischemic period

During severe incomplete brain ischemia caused by combined bilateral ligation of the general carotid arteries and blood pressure reduction to 50 Hg by blood withdrawal from the femoral artery, the cortex of cerebral hemispheres demonstrates, by the 60th minute of ischemia, a 15.4%-lowering of the content of total phospholipids (PL) and a 33.3%-increase in the content of malonyl dialdehyde (MDA). By the 30th minute of the postischemic period the content of total PL remains decreased, the content of monophosphoinositides (MPI) rises by 110.2%, whereas the content of MDA remains high. By the 60th minute of postischemia the content of total PL and MDA returns to the initial levels. However the content of MDA remains high as before.     

ABRA在正常成年大鼠大脑皮质和海马区的表达

目的观察ABRA(Actin binding Rho activator)在成年大鼠大脑皮质和海马中的表达。方法制备成年大鼠脑的冰冻切片,采用共聚焦免疫荧光技术和免疫荧光强度测量检测ABRA在大鼠大脑皮质和海马区的表达。结果 ABRA在神经元的胞核、胞浆、突起内可见,其中胞核着色最强。在大脑皮质,ABRA阳性的神经元胞体和突起广泛分布于皮质的分子层、外颗粒层、外锥体细胞层、内颗粒层、内锥体细胞层、多形细胞层,其免疫荧光强度分别为129.22±16.94、125.39±29.83、117.67±22.50、105.85±17.65、103.90±18.00、100.23±20.38,ABRA阳性细胞率分别为0.51±0.01、0.69±0.02、0.64±0.03、0.58±0.05、0.65±0.09、0.63±0.01。在海马,ABRA均匀分布于海马各部,阳性神经元集中于锥体细胞层,而其阳性突起弥散分布于海马分子层和多形层。海马锥体细胞层、分子层、多形层免疫荧光强度分别为141.19±35.48、53.19±10.38、43.32±9.59,ABRA阳性细胞率分别为0.62±0.04、0.27±0.07、0.25±0.03。结论 ABRA广泛表达于大鼠大脑皮质和海马各层,提示ABRA可能在大鼠这些部位的神经细胞功能活动方面起重要作用。     

Effects of carnosine on systemic hemodynamics and myocardial metabolism in rats in the early postresuscitation period]

It was demonstrated in experiments on male rats that acute lethal blood loss and subsequent resuscitation after 4- and 6-min clinical death induce lipid peroxidation processes, decreased antioxidant enzyme activity, cause activation of anaerobic glycolysis in the myocardium. This metabolic heart impairment causes hemodynamic instability in postresuscitation period. 25 mg/kg of carnosine injected during resuscitation decreased functional-metabolic heart impairments and hemodynamic disarrangement as well as early postresuscitation lethality. The authors attribute positive carnosine effect to its significant antioxidant activity.     

Toxic activity of the blood plasma in the early postresuscitation period

The time course of blood plasma toxicity was studied in dogs in the early postresuscitation period 10 minutes after clinical death because of acute hemorrhage. The duration of dying, the rate of the recovery of the main vitally important body functions were discovered to affect the rate of accumulation in the blood of substances with different molecular weights. There were 3 phases in blood plasma toxicity accumulation. The first phase is marked by the overflow of blood vessels with low-molecular substances, the second one by relative lessening of the content of low-molecular metabolites and an increase in the content of medium-molecular substances. The second phase is in agreement with the maximal rise of blood plasma toxicity. The third phase that develops by the 60th minute of the postresuscitation period is characterized by reduction of the peak activity of all substances under study and by overt toxicity with relative normalization of the main body functions.     

Difference in glutamate release between retina and cerebral cortex following ischemia

The difference in ischemic tolerance between the retina and cerebral cortex may be attributable to a difference in glutamate release during ischemia. Glutamate release in the retina and the cerebral cortex was compared in rats. A dialysis electrode for real-time glutamate measurement was perfused with L-glutamate oxidase, and the current evoked between two voltage-clamped electrodes was detected. Two electrodes were implanted in the retina through the choroid and cerebral cortex in 12 anesthetized rats, each mounted on a stereotaxic frame. Global ischemia was induced by ligation on both carotid arteries and hypotension was induced by blood withdrawal. Under control conditions, the glutamate concentration in the retina was 164 +/- 231 (mean +/- standard deviation) microM, being significantly higher (P < 0.05) than that in the cerebral cortex (83 +/- 105 microM). In 10 of the 12 animals, the glutamate concentration in the retina decreased to a minimum of 134 +/- 149 microM (P < 0.01, compared with the value for the cerebral cortex), but that in the cortex increased to 410 +/- 305 microM (averaged highest value). Immediately after the start of reperfusion, the glutamate concentration in the cortex decreased rapidly to 101 +/- 27 microM, but that in the retina increased gradually to almost the control level (148 +/- 204 microM). In the other two animals, the glutamate concentration remained unchanged. In conclusion, glutamate release in the retina does not proceed as rapidly as that in the cerebral cortex during 20 min of ischemia, and in fact decreases. This opposite trend shown by the two organs may be due to the slow depletion rate of ATP in the retina. This may explain the differing neuronal tolerance to ischemia in these two organs.     

Poppy seed oil protection of the hippocampus after cerebral ischemia and re-perfusion in rats

The brain is highly sensitive to hypoxia; this is true particularly of parts that are crucial for cognitive function. The effects of hypoxia are especially dramatic in the hippocampus. We evaluated the potential protective effects of poppy seed oil on the number of hippocampus cells and the serum antioxidant/oxidant status after cerebral ischemia and re-perfusion (CIR). Eighteen rats were divided into three equal groups. Group 1 served as the control group without CIR. Group 2 received poppy seed oil daily by oral gavage at a dose of 0.4 ml/kg, while group 3 was given 0.4 ml/kg saline solution by oral gavage per day; these treatments were continued for one month. Groups 2 and 3 were subjected to CIR induced by clamps on two points of both of the carotid arteries for 45 min followed by 45 min re-perfusion. There were significant decreases in the number of hippocampus cells between groups 1 and 2, and between groups 1 and 3. The mean cell number in group 2 was not significantly different from that of group 3. The serum nitric oxide levels in CIR groups were elevated significantly compared to controls, and were significantly higher in group 2 than in group 3. The glutathione levels were increased significantly in the poppy seed oil treated group compared to the saline CIR groups. The malondialdehyde levels were markedly increased in group 3 compared to both groups 1 and 2. Our study suggests that poppy seed oil can improve antioxidant defense capacity after CIR, although this treatment did not alter significantly the frequency of cell death.     

Resveratrol preconditioning modulates inflammatory response in the rat hippocampus following global cerebral ischemia

Considerable evidence has been accumulated to suggests that blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Consequently, anti-inflammatory therapies are being explored for prevention and treatment of these diseases. Induction of brain tolerance against ischemia by pretreatment with resveratrol has been found to influence expression of different molecules. It remains unclear, however, whether and how resveratrol preconditioning changes expression of inflammatory mediators after subsequent global cerebral ischemia/reperfusion (I/R). Therefore, we investigated the effect of resveratrol pretreatment on NF-κB inflammatory cascade, COX-2, iNOS and JNK levels in experimental I/R. Adult male rats were subjected to 10min of four-vessel occlusion and sacrificed at selected post-ischemic time points. Resveratrol (30mg/kg) pretreatment was injected intraperitoneally 7days prior to I/R induction. We found that resveratrol treatment before insult remarkably reduced astroglial and microglial activation at 7days after I/R. It greatly attenuated I/R-induced NF-κB and JNK activation with decreased COX-2 and iNOS production. In conclusion, the neuroprotection of resveratrol preconditioning may be due in part to the suppression of the inflammatory response via regulation of NF-κB, COX-2 and iNOS induced by I/R. JNK was also suggested to play a protective role through in neuroprotection of resveratrol, which may also be contributing to reduction in neuroinflammation. The study adds to a growing literature that resveratrol can have important anti-inflammatory actions in the brain.     

Reparative processes in postischemic cerebral cortex in the early postresuscitation period (materials submitted to the International Symposium, "Central nervous system and postresuscitation pathology," Moscow, March 14-16, 1989)

Dynamics of neuronal plasticity in rat postischemic cerebral cortex in the early postresuscitation period following complete ischemia was studied by electron microscopic methods. In this period destructive processes have proved to run parallel with reparative ones in the postischemic cerebral cortex. The phenomenon of true regeneration of cell processes in the cerebral neurons engendering growth cones observed by the third hour of the post-resuscitation period is of particular interest. Subsequently, these signs lead to the formation of new synaptic interneuronal links and new neuronal nets in the cerebral cortex. The data obtained open up new prospects for understanding the pathogenesis of postresuscitation encephalopathies.     

Central hemodynamics of dogs in the early postresuscitation period and the outcome of resuscitation

Variations in central hemodynamics of dogs were compared with the outcome of resuscitation of 18 dogs subjected to 12-minute reversible circulatory arrest because of ventricular fibrillation. Nine survived dogs with completely recovered neurological status during the first 10 minutes after resuscitation had moderate hypertension, the mean arterial pressure (MAP) being 175.0 + 8.9 mm Hg. In the dogs who died within 24-48 hours after resuscitation, the MAP did not rise during this period as compared to the initial level; 2 dogs developed excessive hypertension (MAP about 200 mm Hg). There were also found certain differences in other parameters of central hemodynamics. Moderate hypertension in the first 10 minutes of the postresuscitation period leads to rapid restoration of the adequate level of peripheral blood flow in organs and tissues, thus favouring survival of animals subjected to a long circulatory arrest.     

Altered protein kinase C activity in different subfields of hippocampus following cerebral ischemia

Protein kinase C (PKC) activity was determined in different (membrane, nuclear and soluble) subcellular fractions prepared separately from the CA1 and CA3 subfields ofMongolian gerbils hippocampus at various time intervals following a single 5-min occlusion of the common carotid arteries.Soluble andnuclear PKC activities of the CA1 sector were found to be elevated at 24 hours following the ischemic injury, while PKC activities did not increase in the CA3 region until the 3rd day after ischemia. The ratio ofsoluble/membrane-associated PKC activities followed a similar pattern, predominantly because the activation/elevation and then down regulation of the cytosolic enzyme pool changing correspondingly to the ongoig pathological processes. PKC activity returned to the normal level in each subfraction of the CA3 subfield by the 7th day. However, PKC activity remained elevated in the soluble fraction of the CA1 sector even after the delayed death of pyramidal neurons, presumably because of the reactive response of astrocytes. Conceivably, the transient activation and rapid down regulation of PKC in the CA1 sector may contribute to the initiation of postischemic neuronal death in the CA1 subfield.Abbreviations BSA bovine serum albumin - GFAP glial fibrillary acidic protein - PKC Ca²⁺/phospholipid-dependent protein kinase - PMSE phenylmethylsulfonyl fluoride     

Proline promotes decrease in glutamate uptake in slices of cerebral cortex and hippocampus of rats

In the present study we first investigated the in vitro and in vivo effects of proline on glutamate uptake in the cerebral cortex and hippocampus slices of rats. The action of alpha-tocopherol and/or ascorbic acid on the effects elicited by administration of proline was also evaluated. For in vitro studies, proline (30.0 microM and 1.0 mM) was added to the incubation medium. For acute administration, 29-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or saline (control) and were sacrificed 1 h later. Results showed that addition of proline in the assay (in vitro studies) reduces glutamate uptake in both cerebral structures. Administration of proline (in vivo studies) reduces glutamate uptake in the cerebral cortex, but not in the hippocampal slices of rats. In another set of experiments, 22-day-old rats were pretreated for one week with daily administration of alpha-tocopherol (40 mg/kg) or ascorbic acid (100 mg/kg) or with both vitamins. Twelve hours after the last vitamins injection, rats received a single injection of proline or saline and were killed 1 h later. Pretreatment with alpha-tocopherol and/or ascorbic acid did not prevent the effect of proline administration on glutamate uptake. alpha-Tocopherol plus ascorbic acid prevented the inhibitory effect of acute hyperprolinemia on Na(+),K(+) -ATPase activity in the cerebral cortex of 29-day-old rats. The data indicate that the effect of proline on reduction of glutamate uptake and Na(+),K(+) -ATPase activity may be, at least in part, involved in the brain dysfunction observed in hyperprolinemic patients.