Search

The influence of hyperbaric oxygen (HBO) treatment on the activities of superoxide dismutase (SOD) and Na + ,K + -ATPase was determined during different time periods of reperfusion in rats exposed to global cerebral ischemia. Ischemic animals were either sacrificed or exposed to the first HBO treatment 2, 24, 48 or 168 h after ischemic insult (for SOD activities measurement) or immediately, 0.5, 1, 2, 6, 24, 48, 72 or 168 h after ischemic procedure (for Na + ,K + -ATPase activities measurement). Hyperbaric oxygenation procedure was repeated for seven consecutive days. The results of presented experiments demonstrated the statistically significant increase in the hippocampal SOD activity 24 and 48 h after global cerebral ischemia followed by a decrease in the enzymatic activity 168 h after ischemic insult. In the ischemic rats treated with HBO the level of hippocampal SOD activity was significantly higher after 168 h of reperfusion in comparison to the ischemic, non HBO-treated animals. In addition, it was found that global cerebral ischemia induced a statistically significant decrease of the hippocampal Na + ,K + -ATPase activity starting from 1 to 168 h of reperfusion. Maximal enzymatic inhibition was obtained 24 h after the ischemic damage. Decline in Na + ,K + -ATPase activity was prevented in the animals exposed to HBO treatment within the first 24 h of reperfusion. Our results suggest that global cerebral ischemia induces significant alterations in the hippocampal SOD and Na + ,K + -ATPase activities during different periods of reperfusion. Enhanced SOD activity and preserved Na + ,K + -ATPase activity within particular periods of reperfusion, could be indicators of a possible benefitial role of HBO treatment in severe brain ischemia.

This study aimed to investigate the individual effects of chronic stress and occlusal interference, as well as their combined influence on masseter muscle pain. Experiments were performed on 28 male Wistar rats. Animals were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mantioned procedures. At the end of the procedure animals were submitted to orofacial formalin test, and nociceptive behavioral response was evaluated. Statisticaly significant difference of nociceptive behavioral response in chronicaly stressed rats and in the animals with occlusal interference in comparation to the control group were not obtained (p > 0.05). In contrast, nociceptive behavioral response was significantly increased in rats submitted to both of experimental procedures (p < 0.01). These findings suggest that only combination of occlusal interference and chronic stress influence masseter muscle pain.

To determine the influence of global cerebral ischemia on the activation of extracellular-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) in optic nerves of rats exposed to different reperfusion periods. Transient global cerebral ischemia (20-min duration) was induced by the four-vessel occlusion method. After different reperfusion periods (5 and 10 min ; 1 ; 6 and 12 h after ischemia), optic nerves were extracted and ERK and JNK activation signals were determined by Western immunoblot analyses. The activation signals of ERK and JNK were detected within first 10 min of reperfusion, but striking activation for both enzymes was found 1 h after ischemia. After transient decrease, the activation of ERK returned to peak level after 12 h of reperfusion in the second wave of kinase activation. In that period, slight increase of JNK activation was registered. Our results demonstrated for the first time that ERK and JNK were activated in rat optic nerves during early and later periods of reperfusion, suggesting their potential active role in the response of cerebral white matter tissue to ischemic injury.

The effects of hyperbaric oxygen (HBO) treatment on the Na(+), K(+)-ATPase and superoxide dismutase (SOD) activities were examined in the optic nerves of the rats exposed to global cerebral ischemia. Animals were exposed to global cerebral ischemia of 20-min duration and were either sacrificed or exposed to the first HBO treatment immediately, 0.5, 1, 2, 6, 24, 48, 72 or 168 h after ischemic procedure (for Na(+), K(+)-ATPase activities measurement) or 2, 24, 48 or 168 h after ischemia (for SOD activities measurement). HBO procedure was repeated for 7 consecutive days. It was found that global cerebral ischemia induced a statistically significant decrease in the Na(+), K(+)-ATPase activity of the optic nerves, starting from 0.5 to 168 h of reperfusion. Maximal enzymatic inhibition was registered 24 h after the ischemic damage. The decline in the Na(+), K(+)-ATPase activity was prevented in the animals exposed to HBO treatment within the first 6 h of reperfusion. The results of the presented experiments demonstrated also a statistically significant increase in the SOD activity after 24, 48 and 168 h of reperfusion in the optic nerves of non-HBO-treated ischemic animals as well as in the ischemic animals treated with HBO. Our results indicate that global cerebral ischemia induced a significant alterations in the Na(+), K(+)-ATPase and SOD activities in the optic nerves during different periods of reperfusion. HBO treatment, started within the first 6 h of reperfusion, prevented ischemia-induced changes in the Na(+), K(+)-ATPase activity, while the level of the SOD activity in the ischemic animals was not changed after HBO administration.

Aims: We examined the effects of MK-801 on the Na+, K+-ATPase activity and ERK activation in the rat hippocampal tissue after exposure to global cerebral ischaemia of 20 min duration. Procedure: The enzymatic activity and ERK activation were measured at different time points after ischaemia (30 min: 1: 6: 12: 24: 72 and 168 h for the Na+, K+-ATPase activity measurements/5 and 10 min: 1: 6 and 12 h for ERK activation) in control animals such as in the ischaemic animals pretreated with different doses of MK-801 (0.1: 0.3. 1.0 and 3.0 mg/kg), 30 min before exposure to ischaemia. Results: It was found that global cerebral ischaemia induced a statistically significant decrease in Na+, K+-ATPase activity starting from 1 to 168 h of reperfusion. Maximal enzymatic inhibition was obtained 24 h after ischaemic damage. The activation signal of JNK was detected 5 min up to 12 h after ischaemia, but maximal activation was registered after 1 h of reperfusion. Pretreatment with 1.0 or 3.0 mg/kg of MK-801 prevented the decrease of the Na+, K+- ATPase activity and preserved the level of JNK activation in all experimental groups of the ischaemic animals. Conclusions: Decrease in Na+, K+-ATPase activity such as ERK activation are evident during different periods of reperfusion injury after global cerebral ischaemia. Pretreatment with MK-801 prevented changes mentioned above and indicated its possible beneficial role in the treatment of severe brain ischaemia.

Effects of the hyperbaric oxygen (HBO) treatment on the ERK and JNK activation signals in the hippocampus and optic nerves of rats exposed to global cerebral ischaemia were studied. Animals were exposed to global cerebral ischaemia (20 min duration) and after different reperfusion periods (5 and 10 min ; 1 ; 6 and 12 h after ischaemia), ERK and JNK activation signals were determined. A part of ischaemic animals were exposed to HBO after reperfusion during seven consecutive days, at 222, 86 kPa pressure of 99, 5% oxygen, lasting 60 min. Results: The activation signals of ERK and JNK in hippocampus and optic nerves of the ischaemic animals were registered during all reperfusion periods tested, but maximal activation was found 1 h after ischaemia. In the optic nerves, second strong activation signal was repeated after 12 h of reperfusion. After the HBO treatment, intensity of activation signals was decreased or suppressed during all reperfusion periods tested. Our results indicated that activation of ERK and JNK were implicated in early and a later periods of reperfusion injury such as that pretreatment with HBO may have a possible protective effect in cerebral ischaemia.

Introduction: Cerebral ischemia is determined with several different toxic processes including excitotoxicity, metabolic toxicity and oxidative stress. Because loss of oxygen initiates a variety of intracellular and metabolic changes in cerebral ischemia, an increase in the oxygen delivery to the cerebral tissue might prevent neuronal damage and ameliorate brain recovery after ischemia. Hyperbaric oxygen (HBO) treatment has been considered as a method to improve tissue oxygen delivery. Although the effectiveness of HBO treatment has been controversial for many years, the results presented in some experimental models of cerebral ischemia, such as in a few clinical reports, have been promising. However, the biochemical and molecular mechanisms of such treatment in cerebral ischemia are not extensively studied. The objectives of our study was to determine: a) the influence of global cerebral ischemia on the superoxide dismutase (SOD) activity and JNK activation in the optic nerves at different time points after ischemia and b) to evaluate the effect of HBO treatment after cerebral ischemia on the mentioned parameters. Materials and Methods: Hannover-Wistar rats were exposed to global cerebral ischemia of 20-min duration (Pulsinelli and Brierly, 1979) and were either sacrificed or exposed to the first HBO treatment 2, 24, 48 or 168 h after ischemic procedure (for SOD activity measurements) or 5 and 10 min, 1, 6 and 12 h after ischemia (for determinations of JNK activation). HBO treatment (2 ATA ; 98.5 % oxygen) was repeated for seven consecutive days, once per day. Each treatment lasted for 60 min. Results: The results of the presented experiments demonstrated a statistically significant increase in the SOD activity after 24, 48 and 168 h of reperfusion in the optic nerves of non HBO-treated ischemic animals, as well as in the ischemic animals treated with HBO. The JNK activation in the optic nerves of the ischemic animals was registered after all reperfusion periods tested. Maximal activation was found 1 h after ischemia but second strong activation signal was detected again at 12 h of reperfusion period. HBO treatment decreased the intensity of JNK activation signals during all reperfusion periods tested. Conclusion: Our results indicate that global cerebral ischemia induced a significant increase in SOD activity and that the level of SOD activity in ischemic animals was not changed after HBO administration. Activation of JNK was implicated in early and later periods of reperfusion injury. HBO treatment decreased the level of JNK activation, indicated its possible beneficial role in the treatment of global brain ischemia.

Introduction: Na+K+-ATPase is highly concentrated in neuronal cell membranes and is important for cellular integrity and function. Since its activity is very sensitive to even small changes in the plasma membrane lipid microenvironment, the early and late stages of tissue injury can be studied by measuring its activity. Therefore, the purpose of this study was to investigate the changes of the hippocampal Na+K+-ATPase activity in rats exposed to global cerebral ischemia or in rats with kainic acid-induced seizures. Materials and Methods: Global cerebral ischemia of 20-min duration was induced by the four-vessel occlusion method (Pulsinelli and Brierly, 1979). The animals were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72 or 168 h after ischemic procedure. The level of the Na+K+-ATPase activity was measured during all reperfusion periods examined. The enzymatic activity from the hippocampal tissue was also determined 2 h, 3 and 5 days after single KA injection (8 mg/kg). Results: The global cerebral ischemia induced the significant decline in the Na+K+-ATPase activity in the hippocampus starting from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the ischemic damage. In the model of kainic acid-induced seizures the Na+K+-ATPase activity was significantly decreased the 3rd and 5th day after drug administration. Conclusion: The Na+K+-ATPase hippocampal activity has been changed in the conditions of global cerebral ischemia and kainic acid-induced seizures. The observed enzymatic changes could be used as the parameters of tissue damage in mentioned experimental conditions.

The whole brain free fatty acid (FFA) level, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined in the frontal cortex, cerebellum, hippocampus, and pons-medulla region of the single pentylenetetrazol (PZT)-treated and PZT-kindled Hannover-Wistar rats. PZT administration in the convulsive dose caused significant increase of the brain FFA content. Decreased SOD activity was detected in the frontal cortex of PZT-kindled rats, whereas decreased GPX activity was found in the frontal cortex and cerebellum of all treated rats, as well as in the hippocampus and pons-medulla of PZT-kindled rats. Kindling caused distinctive change of antioxidative defense in the frontal cortex, hippocampus, and pons-medulla region.

The influence of 20 min global cerebral ischemia on the free arachidonic acid (FAA) level and Na+, K+-ATPase activity in the rat hippocampus at different time points after ischemia was examined. In addition, the effect of MK-801 on mentioned parameters was studied. Animals were exposed to 20 min global cerebral ischemia and were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72, and 168 h after ischemic procedure. The level of the FAA and the Na+, K+-ATPase activity was measured during all reperfusion periods examined. Various doses of MK-801 (0.3, 1.0, 3.0, and 5.0 mg/kg) had been injected 30 min before ischemic procedure started. It was found that 20 min global cerebral ischemia induces a statistically significant increase of the FAA level immediately after ischemia and during the first 0.5 h of reperfusion. After a transient decrease, the level of FAA level increased again after 24 and 168 h of recirculation. Treatment with 3.0 mg/kg of MK-801 significantly prevented the FAA accumulation immediately and 0.5 h after ischemic insult while application of 5.0 mg/kg of MK-801 exerted a protective effect during the first 24 h. Global cerebral ischemia induces the significant decline in the Na+, K+-ATPase activity in the hippocampus starting from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the ischemic damage. Application of 3.0 mg/kg of MK-801 exerted statistically significant protection during the first 24 h while the treatment with 5.0 mg/kg of MK-801 prevented fall in enzymatic activity during all reperfusion periods examined. Our results suggest that, in spite of different and complex pathophysiological mechanisms involved in the increase of FAA level and the decrease of the Na+, K+-ATPase activity, blockade of NMDA receptor subtype provides a very important strategy for the treatment of the postischemic excitotoxicity.

Seizures trigger a variety of biochemical processes including an influx of extracellular Ca2+, activation of membrane phospholipases, liberation of free fatty acids, diacylglycerols, eicosanoids, lipid peroxides and free radicals. These lipid metabolites along with abnormal ion homeostasis may be involved in cell injury and cell death. The aim of this study was to determine brain antioxidant enzyme activities in rats with electroconvulsive shock (ECS)-induced seizures. ECS, single or repeated, induced a decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in various brain regions. The most prominent changes of enzymatic activities were observed in rats that received five ECSs with 24-h recovery period between them. Decreased SOD activity was observed in the frontal cortex of all treated animals except those sacrificed 24 h after single ECS, in the cerebellum of the animals that received repeated ECSs, in the hippocampus of animals that were decapitated 2 h after a single ECS and in the pons–medulla region of rats that received five daily ECSs. Decreased GPX activity was found in all examined brain regions of the rats that received five ECSs, the cortex and hippocampus of rats that were decapitated 2 h after single ECS and the cortex of those that received 10 ECSs with 48 h between them. The results show that neither 24-h nor 48-h recovery period was sufficient for the normalisation of antioxidative enzyme activities after repeated ECS treatment.

Preserved morphological and functional cell membrane integrity is fundamental for normal functioning of brain cells. Seizure activity, when continued for a sufficient time, induces neuronal death. Seizures trigger a variety of biochemical processes including an influx of extracellular Ca2+ , activation of membrane phospholipases, liberation of free fatty acids (FFA), diacylglycerols, eicosanoids, lipid peroxides and free radicals. These lipid metabolites along with abnormal ion homeostasis may be involved in cell injury and death. Pentylenetetrazol (PTZ) is one of the most often used epileptic agents in antiepileptic drug screening protocols. The aim of our study was to determine the influence of PTZ- induced seizures on the brain FFA level and learning ability in rats. Some animals received PTZ (50 mg/kg i.p.) and were decapitated 5 minutes after the appearance of epileptic seizures. The brains were quickly removed and samples were taken from cerebral cortex, cerebellum, hippocampus and pons-medulla oblongata. Lipids were extracted from the whole brains and specific regions. FFA were separated using TLC and after methylation quantified by gas chromatography. The other animals were trained in a passive avoidance procedure and received PTZ immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. The results of our experiments have shown that PTZ produced seizure activity 5 minutes after the application, but did not influence neither brain FFA content nor the passive avoidance behaviour in rats. Obtained data suggests that PTZ in doses sufficient for seizure induction did not produce significant changes in the level of investigated biochemical parameters and learning ability in rats.

Cerebral hypoxia is associated with increase of intracellular calcium concentration and free arachidonic acid (FAA) level and followed by various behavioral disturbances. The aim of this study was to investigate the effect of calcium channel blockers, nicardipine and ifenprodil, on the brain FAA level and learning ability in rats exposed to hypoxia. The study was carried out on Hannover-Wistar rats weighing 250 g. They were injected with 0, 03 ; 0, 1 ; 0, 3 or 1 mg/kg of tested drugs i.p. Thirty minutes later the learning ability was tested in a passive avoidance task according to the step-through procedure. Immediately after the training trial, the animals were subjected to a period of oxygen deprivation hypoxia until loosing of the righting reflex. The retention trial was carried out 24 hours later. Other group of animals was pretreated with mentioned substances before hypoxia-exposure. Fifteen minutes after losing of the righting reflex they were decapitated and brains were frozen in liquid nitrogen. The FAA level was quantified by gas chromatography. Our results show that both nicardipine and ifenprodil were effective in preventing a memory decline in hypoxia-exposed rats. Nicardipin did not prevent the accumulation of the brain FAA contrary to ifenprodil which produced statistically significantly decrease of the brain FAA level in hypoxia-exposed rats.

1. 1. The influence of voltage dependent calcium channel blocker (VDCC), nimodipine and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 on the brain free arachidonic acid (FAA) level and on the learning ability in hypoxia-exposed rats was examined. 2. 2. Some animals were decapitated after cerebral hypoxia had been obtained and the brain FAA level was determined by gas chromatography.The other animals were trained in a passive avoidance procedure and were exposed to hypoxic conditions immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. 3. 3. Various doses of nimodipine (0.03;0.1;0.3 and 1.0 mg/kg) and MK-801 (0.03;0.1 and 0.3 mg/kg) had been injected 30 minutes before biochemical or behavioral procedures started. 4. 4. It was found that hypoxia strongly increased the brain FAA level and impaired the retention of the passive avoidance response. 5. 5. Pretreatment with 0.3 mg/kg and 1.0 mg/kg of nimodipine prevented the brain FAA accumulation. It has also been shown that all tested doses of nimodipine significantly improved the retention deficit in the animals exposed to hypoxia. 6. 6. Neither the one of tested doses of MK-801 influenced significantly the increase of the brain FAA level and/or passive avoidance behavior in hypoxic animals. 7. 7. These results confirm the hypothesis that the brain FAA accumulation and cognitive impairment, caused by hypoxia, are maybe associated with disturbances in calcium homeostasis and that nimodipine may be useful in ameliorating the hypoxia-induced brain tissue damage. Blocade of NMDA receptor-channel complex by MK-801 was not sufficient to prevent hypoxia-induced neuronal damage.

Cerebral hypoxia accompanies various clinical situations that are manifested with impairment of cognitive processes, especially memory functions. We hypothetized that disturbance in Ca2+ homeostasis might contribute to the memory deficits associated with cerebral hypoxia and that the pharmacological inhibition of the Ca2+ entry into the cells could antagonize cognitive deficits. Therefore in this study we examined the influence of nimodipine and MK-801 on the retention of passive avoidance in rats exposed to hypoxia. The study was carried out on Hannover- Wistar rats weighing 250 g. Various doses (0, 03 ; 0, 1 ; 0, 3 mg/kg) of nimodipine or MK-801 were administered intraperitoneally. Thirty minutes later the passive avoidance task was performed according to the step-through procedure. Immediately after the training trial the animals were subjected to the period of oxygen deprivation hypoxia. Twenty four hours later passive avoidance retention was tested. It was found that hypoxia strongly impaired the retention of the passive avoidance response. Nimodipine significantly improved the retention deficits in hypoxia-exposed rats while MK-801 was ineffective.

Kainic acid (KA) is an excitatory glutaminergic agonist that given intrahippocampally induces seizures. The EEG changes show spike activity originating in limbic system associated with the increase in EEG power spectra. The aim of our study was to investigate whether nimodipine and nicardipine could prevent KA-induced changes in EEG activity. Experiments were performed on adult Wistar rats. They were anesthetized and placed in a stereotaxic apparatus. Vehicle, nimodipine or nicardipine (1, 3, 10 and 30 mg/kg) had been given 30 minutes prior to intrahippocampal injection or KA (15 nmol). In each rat four screw electrodes were placed over the frontal and parietal cortex. The EEG was recorded in basal conditions and 5, 10, 15, 30 and 60 minutes after KA administration. In order to obtain EEG samples for frequency analysis. the output of EEG machine was amplified and was transmitted to an IBM AT-compatible microcomputer via analog-to-digital converter. The system was calibrated using 500 V. In order to obtain power spectra between 0-30 Hz, two 7.5 s samples of artefact free EEG were analysed. Spectral averages were computed using Fast Fourier Transform. Individual power of each frequency bin was normalised to average total power of baseline. EEG frequencies were collapsed in 1 Hz bins. Our results demonstrate that nicardipine was not effective while nimodipine in doses of 10 and 30 mg/kg prevented KA-induced excitatory changes in EEG and EEG power spectra.

Cerebral hypoxia is an important causal factor of memory disturbances. The present study was designed to determine the efficacy of acetylcholinesterase inhibitor tetrahydroamino- acridine (THA) in preventing the memory decline in hypoxia-exposed animals. The study was carried out on Hannover Wistar rats weighing 250 g. Various doses of THA (0.1 ; 0.3 ; 1.0 mg/kg) were given i.p. Sixty minutes later passive avoidance task was performed according to the step-through procedure. Immediately after the training trial, animals were subjected to a period of oxygen deprivation hypoxia. The level of 3.5 V% of oxygen was reached in about twenty minutes and maintained up to the loss of righting reflex. The retention trial was carried out 24 hours later. It has been found that all tested doses of mentioned cholinergic agent led to a significant enhancement of the passive avoidance in hypoxia treated rats. Our results confirm the hypothesis that increase of central cholinergic activity can antagonize memory decline in hypoxia-exposed rats.

Although considerable efforts have been directed toward characterizing the pathophysiological and neurochemical aberrations produced by hypoxia, the precise mechanisms of the ensuing brain dysfunction remain unclear. There are, however, good evidences that a variety of central nervous system changes are associated with hypoxia, including alterations of electrolyte homeostasis, depletion of energy stores, acidosis, lactacidosis, changes of blood-brain barrier permeability, decrease in membrane phospholipid content., increase of intracellular free fatty acid (FFA) pool, and the formation of free radicals. The FFAs, especially free arachidonic acid (FAA), are assumed to have detrimental effects on mitochondrial and plasma membrane functions, leading into a membrane dissolution, a production of vasoconstrictive prostaglandines and tromboxanes and an increase in neurotransmitter release. All these factors may contribute to vasoconstriction, impairment of posthypoxic reperfusion, brain vessel damage and cerebral edema, ultimately leading into the neuronal death. The present study was undertaken to examine dynamics of brain free palmitic, stearic, oleic and FAA during various time intervals after hypoxic brain injury. The study was carried out on Hannover-Wistar rats, weighing 250 g. The animals were subjected to 3.5 V% hypoxia, until loosing of righting reflex. Immediately or 5 or 15 or 60 minutes after hypoxia animals were decapitated, brains were removed quickly and frozen in the liquid nitrogen. Lipids were extracted from frozen brains and fractionated by TLC. Fatty acid methyl esters were prepared by methanolysis and quantified by GLC using internal standard method. Our results clearly demonstrated that cerebral hypoxia induced progressive increase in the brain FFA acid content. Palmitic, stearic and oleic acids show same liberation pattern, reaching statistically significant level 60 minutes after the loosing of righting reflex. Maximal level of the FAA was detected 15 minutes after cerebral hypoxia had been obtained. Sixty minutes after hypoxia procedure the level of mentioned free fatty acid decreased to the control value. It could be concluded that cerebral hypoxia induced different liberation modes of individual FFAs.

Kainic acid (KA) is an excitatory glutaminergic agonist that given intrahippocampally induces seizures. The EEG changes show major spike activity originating in limbic system. The aim of our study was to investigate whether nimodipine could prevent KA-induced changes in EEG activity. Experiments were performed on adult Wistar rats. They were anesthetized and placed in a stereotaxic apparatus. Vehicle or nimodipine (30mg/kg) had been given 30 minutes prior to intrahippocampal injection of KA (15 nmol). In each rat four screw electrodes were: placed over the frontal and parietal cortex. The EEG was recorded in basal conditions and 5, 10, 15, 30 and 60 minutes after KA administration. In order to obtain EEG samples for frequency analysis, the output from the EEG machine was amplified and was transmitted to all IBM AT-compatible microcomputer via analog-to- digital converter. The system was calibrated using 500 V. Two 7.5 s samples of artefact free EEG were analyzed. In order to obtain power spectra between 0-30 Hz spectral averages were computed using Fast Fourier Transform. Individual EEG power of each frequency bin was normalized to average total power of baseline EEG frequencies were collapsed into 1 Hz bins. Our results demonstrate that nimodipine was effective in the prevention of changes in EEG activity induced by intrahippocampal KA administration.

The influence of nicardipine on the brain free arachidonic acid (FAA) level and on the learning ability in hypoxia-exposed rats was examined. The study was carried out on Hannover-Wistar rats weighing 250 g.They were injected with various doses (0.03 ; 0.1 ; 0.3 or 1.0 mg/kg) of nicardipine. Thirty minutes later some animals were subjected to the period of oxygen deprivation hypoxia until the loss of the righting reflex. Fifteen minutes later they were decapitated and brains were frozen in liquid nitrogen. The level of the brain FAA was quantified by gas chromatography. The learning ability of all other animals pretreated with the calcium channel blocker used, was tested in a passive avoidance task according to the step-through procedure. These animals were exposed to the hypoxic conditions immediately after the learning trial response had been aquired. A passive avoidance retention test was performed 24 hours later. It was found that hypoxia strongly increased the brain FAA level and impaired the retention of the passive avoidance response. Nicardipine did not influence the content of the brain FAA, but significantly improved the retention deficits in the animals exposed to hypoxia.

In this paper the influence of tetrahydroaminoacridine on electro-shock induced amnesia in the rat was investigated.

A disturbance in Ca2+ homeostasis induced by hypoxia causes numerous intracellular changes including phospholipases activation and free fatty acids (FFAs) liberation. These effects start the "arachidonic acid (AA) cascade" with concomitant detrimental action on cell structure and functioning. The aim of our study was to determine the influence of indomethacin, cyclooxygenase inhibitor, on FFA pool in hypoxia-exposed rats. The study was carried out on Hannover-Wistar rats weighing 250 g. The animals of control group were intact, drug naive. All other rats were subjected to a period of oxygen deprivation hypoxia until loosing righting reflex and decapitated 15 or 60 minutes later. Two groups of animals were injected with vehicle solution. Other two groups were pretreated with 10 mg/kg of indomethacin, i. p. 30 minutes before hypoxia exposure. FFAs were quantified by gas chromatography using internal standard method. Our results demonstrate that indomethacin significantly increases total FFA level in hypoxic rats decapitated 15 minutes after the hypoxia-exposure, with no changes in free AA content. On the contrary, the increase in the brain free AA level and no change in total FFA level was observed in hypoxic animals decapitated 60 minutes after hypoxia.

Kainic acid (KA) is an excitatory glutaminergic agonist that induces epileptic seizures. The purpose of this study was to record EEG activity and the behavioral pattern changes after an intrahippocampal KA administration. Experiments were performed on adult Wistar rats. The animals were anesthetized and placed in a stereotaxic apparatus. Surface screw electrodes were placed over the frontal and parietal cortex. KA was administrated into the left dorsal hippocampus. The EEG activity was recorded in a basal conditions and 5, 10, 15, 30 and 60 minutes after the KA application. During this period complex behavioral pattern was also observed. EEG samples were digitized and subjected to computerized frequency analysis. The KA-induced excitatory changes in EEG activity were followed by complex behavioral syndrome that lasted for several hours. It has been concluded that intrahippocampal injection of kainate may be a useful experimental model for investigations of partial seizures with complex simptomatology (temporal lobe seizures disorders).

Chemically induced seizures in animals are accompanied with the increase in cerebral free fatty acids (FFAs) as a result of their liberation from membrane phospholipids. This process is mediated by phospholipases that could be stimulated by the increase of intracellular Ca2+ concentration. The FFAs, particulary arachidonic acid, are assumed to have detrimental effects on mitochondrial and plasma membrane functions. The aim of this study was to investigate the effect of the calcium channel blocker, amlodipine, on the brain FFA level in penicillin-induced seizures in rats. The study was carried out on Hannover-Wistar rats. The animals were anesthetized and placed in a stereotaxic apparatus. Each of them received an injection of penicillin (5000 5/l) into the left lateral ventricle. Various doses of amlodipine (1, 3, 10 or 30 mg/kg) had been injected i.p. 30 minutes prior to penicillin application. The rats were decapitated five minutes after the appearance of epileptic seizures. FFAs were quantified by gas chromatnaruphv. Our results demonstrate that intracerebral penicillin administration induced significant increase increase of the brain FFA level, It has also been found that amlodipine did not prevent penicillin induced accumulation of the brain FFAs.

The influence of nootropic drugs, piracetam and oxiracetam, on passive avoidance behavior in intact and hypoxia-exposed rats was examined. Various doses of the drugs tested were injected 60 minutes before the learning trial. Some of the animals were exposed to controlled hypoxic conditions immediately after the learning trial response had been acquired. Twenty four hours later, the passive avoidance retention test was performed. Hypoxia was found to cause a statistically significant impairment in the retention of passive avoidance response. Piracetam and oxiracetam did not influence passive avoidance behavior in intact animals. On the contrary, all tested doses of the substances examined significantly improved the learning ability in the rats in which cognitive deficiency was caused by hypoxia. It was also found that the effect of the drugs tested were dose-dependent. The authors suggest that piracetam and oxiracetam could be used as a therapeutic agents for the treatment of cognitive disturbances due to cerebral hypoxia.

The brain has a high metabolic rate, but low oxygen stores and small reserves of high-energy phosphates and carbohydrates. Therefore, it is very sensitive to hypoxia and ischemia, that constitute important, basic pathophysiological mechanisms of brain damage. It is well documented that selective vulnerability of various brain regions exists in hypoxic or ischemic conditions. Moreover, recent reports strongly suggest that hippocampal pyramidal neurons of the CA1 subfield are extremely vulnerable to hypoxia/ischemia that often results in irreversible damage and neuronal death. The purpose of this study was to investigate the influence of hypoxia/ischemia on the integrity of the hippocampal neurons of CA1 region. The study was carried out on Hannover- Wistar rats, weighing 250 gr. One group of the animals was subjected to a period of oxygen deprivation hypoxia. Namely, the rats were placed into the hypoxia cage and the percentage of oxygen was gradually reduced and continuously measured. The level of 3.5 V% of oxygen was reached in about twenty minutes and maintained up to the loss of righting reflex. The second group of the animals was anesthetized with pentobarbital sodium (50 mg/kg, i.p.). Right common carotid artery was occluded and unilateral cerebral ischemia was produced. Seven days after described experimental procedures the brains were perfused transcardially with 10% formalin under pentobarbital anesthesia, according to the technique of Wolf (1971) . The removed brains were postfixed, dehydrated and embedded in paraffin using standard procedures. Coronal sections, 6 m thick, were stained with hematoxylin and eosin. The number of neurons per 1 mm linear length stratum pyramidale (neuronal density) of the hippocampal CA1 subfield was counted and compared with the results of the control group (intact animals). The preliminary results of our study show that hypoxia does not influence, but unilateral occlusion of common carotid artery produces statistically significant decrease in pyramidal cells density of CA1 hippocampal region.

The effects of various doses (0.03, 0.1, 0.3 or 1 mg/kg) of the calcium channel blockers nicardipine, felodipine and nifedipine on the learning ability in intact rats and on hypoxia-induced retention deficits were examined. All animals were trained in a passive avoidance procedure. The drug tested had been injected 30 minutes before the learning trial started. Some animals were exposed to a hypoxic condition immediately after the learning trial response had been acquired. A passive avoidance retention test was performed 24 hours later. It was found that hypoxia strongly impaired the retention of the passive avoidance response. Nicardipine, felodipine and nifedipine did not influence the passive avoidance behavior in the intact animals, but significantly improved the retention deficits in the animals exposed to hypoxia. The effects of the substances tested were dose-dependent. These findings support the hypothesis that perturbations in calcium homeostasis can contribute to the memory deficits associated with hypoxic conditions.

The ventromedial globus pallidus and adjacent magnocellular neurones of basal forebrain (NB) provide the major cholinergic innervation to the neocortex in the rat. The purpose of this study was to examine the passive avoidance behavior twenty days and six months after the NB lesion. Male Wistar rats weighing 200-250 g were used. Unilateral or bilalateral electrolytic NB lesions were made stereotaxically. The site of the lesions was histologically verified. Twenty days later the passive avoidance task according to the procedure of Ashford and Jones (1976) was performed. A chamber with a grid floor continuously electrified was used. The central area of the platform contained a wooden platform. Each rat was placed on the platform and left in the apparatus for three minutes. The total time spent on the platform was recorded. A total of four consecutive daily sessions were given. Six months later the passive avoidance task was repeated in bilateral lesioned rats. Results of our experiments show that both unilateral and bilateral lesions of the NB impaired the passive avoidance responses in the rat. The effect of bilateral lesions was statistically significant. Six months later significant improvement of passive avoidance behavior was noted in bilateral lesioned rats. It is concluded that destruction of the NB neurons can be compensated by the plasticity of the residual NB neurons and other central cholinergic and noncholinergic structures which are involved in learning and memory processes.

Many cognitive processes, especially memory functions are altered in cerebral hypoxic condition. Numerous evidences suggest that cholinergic neurotransmission activity of central nervous system is strongly involved in memory processes and particularly vulnerable to hypoxia. Therefore, the present study was designed to examine if hypoxia induced amnesia could be reversed by cholinergic agonist arecoline. The study was carried out on Hannover-Wistar rats weighing 250 g. Arecoline (0.1 ; 0.3 ; 1.0 mg/kg) was given i.p. The control group received saline i.p. Ten minutes later passive avoidance behavior was studied according to the step-through procedure. A two compartment apparatus with a grid floor which could be electrified was used. During the learning trial the rat was placed in the illuminated compartment. Ten seconds later the guillotine door was raised and the latency between the door opening and the entrance into the dark compartment was measured. After entering into the dark part of .the apparatus, the animals received an unavoidable foot shock. Immediately after the training, the rats were subjected to a period of oxygen deprivation hypoxia. The retention trial was carried out 24 hours later. Our results demonstrate that hypoxia produced significant impairment of passive avoidance behavior. Arecoline was effective in reversing the memory deficits in hypoxia exposed rats. Namely, all tested doses of mentioned drug produced significant improvement of the passive avoidance task in hypoxic animals. These results support the hypothesis that impairment of cholinergic neurotransmission activity is involved in memory deficit in hypoxic rats.

Influence of oxiracetam on passive avoidance behavior in scopolamine treated rats.

CerebraI hypoxia is associated with a various functional disturbances and damage of neurons. The most important consequence is an influx of calcium from the extracellular to the intracellular compartment. Consequently vascular and metabolic disturbances occur. Therefore, we investigated the effects of calcium channel blockers (nimodipine, nicardipine) and metabolic enhancers (piracetam, oxiracetam) on hypoxia induced cognitive deficit in the rat. The study was carried out on Hannover- Wistar rats weighing 250 gr. Various doses of nimodipine and nicardipine (0.03 ; 0.1 ; 0.3 ; 1, 0 mg/kg) or piracetam (30 ; 100 ; 300 mg/kg) or oxiracetam (50 ; 100 ; 300 mg/kg) were given intraperitoneally. Thirty or sixty minutes later passive avoidance task was performed according to the step-through procedure modified by Jarvik and Kopp (1967). Immediately after the training, animals were subjected to a period of oxygen deprivation hypoxia. Rats were placed into hypoxia cage and the percentage of oxygen was gradually reduced and continously measured. The level of 3, 5 V% of oxygen was reached in about twenty minutes and maintained up to the loss of righting reflex. Twenty four hours later passive avoidance retention was tested by using mentioned step- through procedure. It has been found that all tested drugs were effective in reversing the memory deficits in hypoxia exposed rats. All tested doses of mentioned substances led to significant enhancement of the passive avoidance in hypoxia treated rats.

Dihydropyridine calcium channel blocker, nimodipine may affect memory processes. Thererore, the purpose of the present research was to examine the effects of nimodipine on electro-shock (ECS) induced amnesia in the rat. The study was carried out on Hannover-Wistar rats weighing 150-200 g. Nimodipine (0.03 ; 0.1 ; 0.3 ; 1.0 mg/kg) was given i.p. The control group received saline i.p. Thirty minutes later passive avoidance task was performed according to the step-through procedure. Namely, the rats were placed individually into the light compartment of a two-compartment apparatus. When they walked into the dark compartment they received a foot-shock. Immediately after the training trial the animals received an ECS through the ears. One group of rats was subjected to the same procedure but without ECS (sham ECS treated control group). Twenty-four hours later the retest step-through latency was measured. It has been found that ECS administered to vehicle treated animals immediately after the training trial caused statistically significant decrease of the retest latency as compared to sham ECS treated control animals. Our experiments also demonstrated that pretreatment with nimodipine prevented in a dose-dependent manner the disruption of the avoidance response caused by ECS application. Statistically significant effects were produced by 0.1 ; 0.3 and 1.0 mg/kg nimodipine. These results support the hypothesis that perturbations in calcium homeostasis may contribute to the memory deficits associated with ECS application.

The nucleus basalis magnocellularis (NBM) is the source of cholinergic afferent fibers innervating the rat neocortical regions. It has been known that intact cholinergic system is a prerequisite to unimpaired performance in learning and memory tasks. Therefore lesions of then NBM cause a marked loss of cognitive functions. There are some evidences that dihydroergotoxine (DHE) can also influence cholinergic neurotransmission activity (Le Poncin-Lafitte et al., 1985 ; Amenta et al., 1988). Lecithin is a precursor of acetylcholine and arecoline is direct muscarinic agonist. The purpose of this study was to analyze the influence of mentioned drugs on passive avoidance behaviour in rats with the NBM lesions. Bilateral electrolytic NBM lesions were made on Wistar albino rats weighing 350-450 g. The coordinates for the NBM lesions were 1.8 mm anterior to the bregma, 2.5 mm lateral to midline and 7.0 mm below the dura. 15 days after the surgery the rats started passive avoidance test per the procedure of Ashford and Jones (1976). A chamber with a electrified grid floor was used. The central area of the floor contained a wooden platform. Each rat was placed on the platform and left in the apparatus for 3 min. The total time spent on the platform was recorded. A total of 4 consecutive daily sessions were given. Passive avoidance behaviour in the NBM lesioned rats under the influence of various drugs was measured. The control animals received 0.9% solution. Other rats received DHE methanesulfonate (0, 01 ; 0, 1 ; 1 ; 10 ; 50 mg/kg or lecithin (250 mg/kg) or arecoline hydrochloride (1 mg/kg) or the combinations of mentioned cholinornimetics with DHE (0, 1 mg/kg) All tested drugs were given intraperitoneally, once per day in the course of 4 testing days. Arecoline had been injected 10 and lecithin and DHE 60 minutes before the passive avoidance experiment started. The results of our experiments indicate that: 1.) among the tested doses of DHE only the dose of 0.1 mg/kg caused mild, but not statistically significant improvement in passive avoidance behaviour in the NBM lesioned rats and that 2.) lecithin and arecoline alone or in the combinations with tested dose of DHE were effective in reversing the memory deficits in rats with lesions of the NBM.

Cerebral hypoxia causes various functional disturbances and damage of neurons in central nervous system. Among the theories to explain neuronal damage due to hypoxia, one of the most widely considered is the intracellular accumulation of calcium ions. One of the major mechanisms for regulating calcium entry into the cells is through the 'L' type of voltage sensitive calcium channels. These channels can be modulated by various drugs that have been claimed to counteract the disturbances in calcium homeostasis and prevent massive influx of calcium ions. Among them dihydropyridines (DHP) are considered as the most potent. Therefore, the purpose of this study was to investigate the effects of various types of DHP on passive avoidance in hypoxia exposed rats. The study was carried out on Hannover Wistar rats weighing 250 g. The passive avoidance task was performed according to the modified procedure of Jarvik and Kopp (1967). On the first training day the rats were trained to escape the punishment in step-through passive avoidance task. Immediately after the training trial the animals were subjected to a period of oxygen deprivation hypoxia. Passive avoidance retention was tested twenty-four hours later. The behaviour in hypoxia exposed rats under the influence of drugs was measured. The control animals received vehicle solution and others were pretreated with various doses (0.03 ; 0.1, 0.3 ; 1.0 mg/kg) of nimodipine, nifedipine and amlodipine, intra peritoneally, 30 minutes before the first day training session. The results of our experiments show that hypoxia strongly impaired the passive avoidance behaviour in the rat. Namely, retest latencies in hypoxia exposed rats were significantly lower than those of the control animals. Nimodipine, nifedipine and amlodipine administration increased the passive avoidance in hypoxia exposed rats. Statistically significant effects were produced by all tested doses of nimodipine and amlodipine and by nifedipine with doses of 0.1 ; 0.3 and 1.0 mg/kg. It has also been found that the effects of nimodipine were dose dependent.

Penicillin applied into the motoric cortex may induce focal spike activity. The aim of our study was to investigate whether amlodipine could prevent penicilIin induced excitatory changes in EEG activity. Experiments were performed on adult Wistar rats. They were anesthesized and placed in a stereotaxic apparatus. Vehicle or amlodipine (1 ; 3 ; 10 or 30 mg/kg) had been given 30 minutes prior to penicillin injection (2000 I.U.) into the left motoric cortex. In each rat four screw electrodes were placed over the left or right frontal and parietal cortex. The EEG was recorded in basal conditions and 5, 10, 15, 30 and 60 minutes after penicillin administration. The output from EEG machine was amplified and was transmitted to an IBM AT-compatible computer. The system was calibrated using 500 mV. Two 7.5 s samples of artefact free EEG were analyzed. In order to obtain power spectra between 0-30 Hz spectral averages were computed using Fast Fourier Transform. Individual EEG power of each frequency bin was normalized to average total power baseline. EEG frequencies were collapsed into 1 Hz bins. Our results demonstrate that amlodipine in doses of 10 and 30 mg/kg prevented the rise of EEG power spectra induced by focal penicillin administration.

Hypoxic damage of cell is associated with a precipitous influx of calcium from the extracellular to the intracellular compartment, and as a consequence, intracellular calcium concentration is increasing. The elevated cytosolic calcium concentration induces different vascular and biochemical disturbances like reduction in cerebral blood flow, impairment of the mitochondrial function with concomitant energy failure etc. Calcium entry blockers appear to inhibit calcium entry into cells by so-called slow channels and prevent metabolic disturbances and calcium homeostasis failure. The purpose of this study was to examine the effects of nicardipine and nitrendipine on learning ability in hypoxia exposed rats. The study was carried out on Hannover Wistar rats weighing 250 g. Various doses (0.03 ; 0.1 ; 0.3 ; 1.0 mg/kg) of nicardipine and nitrendipine were given intraperitoneally. Thirty minutes later passive avoidance task was performed according to the step-through procedure, modified by Jarvik and Kopp (1967). Immediately after the training animals were subjected to period of oxygen deprivation hypoxia. Rats were placed into hypoxia cage and the percentage of oxygen was gradually reduced and continuously measured. The level of 3.5 V% of oxygen was reached in about twenty minutes and maintained up to the loss of righting reflex. Twenty four hours later passive avoidance retention was tested by using mentioned step-through procedure. It has been found that both nicardipine and nitrendipine were effective in reversing the memory deficits in hypoxia exposed rats. All tested doses of nitrendipine and 0.3 or 1.0 mg/kg of nicardipine led to a significant enhancement of the passive avoidance in hypoxia treated rats. Nicardipine at the doses of 0.03 or 0.1 mg/kg slightly, but not significantly improved the performance of behavioral task. In conclusion, our results demonstrate that tested calcium entry blockers exerted protective effects against hypoxia induced memory disturbances.

In the present study we examined the structural integrity of the myelin sheath in the peripheral nerves from short-term streptozotocin (STZ)-treated diabetic rats, using ESR spectroscopy as a tool in determining the dynamic state and the structure of the myelin lipid phase. Experiments were performed on spin-labeled sciatic and sural nerves from STZ-treated Hannover–Wistar rats and age-matched controls. The spectrum analysis employed a numerical simulation model with the set of fitting parameters that in the same time relate the ESR line shape and structure and dynamics of the probed environment. The simulation considered three spectral components weighted and summed in the composite spectrum. The comparative analysis of results showed the fraction of the spectral component II to be significantly increased in the spectra of diabetic rats, indicating the significant increase in overall fluidity of the myelin structure. The origin of fluidity changes was further investigated using an experimental model for demyelination (local injection of ethidium bromide in vivo), proteolytic action of trypsin in vitro, and osmotic myelin swelling in vitro. Analysis and comparison of the results suggested a conclusion in terms of changed biophysical properties of the myelin lipid phase in peripheral nerves in the pathology of diabetes.

Research spanning the past several decades suggests that acetylcholine-containing neurons may play an important role in mediating learning and memory in animals and humans. It has been shown that a large cholinergic pathway projecting to cortical areas originates from neurons located in the ventro-medial portion of the pallidum (also known as nucleus basalis (NB) magnocellularis). Electrolytic or neurotoxic lesions of the NB in the rat bring about the degeneration of the cholinergic neurons constituting approx. 90% of its neuronal population. It was of interest to study the influence of unilateral or bilateral electrolytic lesions of the NB on the passive avoidance behaviour in rats. Anesthetized male Wistar rats weighting 200-250 g (3-4 months old) or 350-480 g (about 1 year old) were placed in a stereotaxic apparatus. The coordinates for unilateral or bilateral NB lesions for adult animals were: 1.8 mm anterior, 2.5 mm lateral and 8 mm ventral with bregma as 0. For young rats the used coordinates were: 0.7 mm posterior ; 2.7 mm lateral and 8 mm ventral with bregma as 0. The site of the lesion was histologically verified. Fifteen days later the passive avoidance task according to the procedure of Ashford and Jones (1976) was performed. A chamber with a grid floor continuously electrified was used. The central area of the floor contained a wooden platform. Each rat was placed on that platform and left in the apparatus for 3 minutes. The total time spent on the platform was recorded. A total of 4 consecutive daily sessions were given. Results of our experiments show that both unilateral and bilateral electrolytic lesions of the NB impaired passive avoidance responses in young and old rats.

The nucleus basalis (NB) provides the primary cholinergic input to the cortical mantle. Destruction of these neurons produces marked decrease in choline acetyltransferase and acethylcholinesterase activity, in high-affinity choline uptake of the neocortex and cognitive deficit. Therefore the purpose of this study was to investigate the effect of cholinomimetics (arecoline, lecithin) and nootropic drug piracetam on the passive avoidance behavior in the NB lesioned rats. The study was carried out on Wistar albino rats weighing 200-250 g. Anesthetized rats were placed in a stereotaxic apparatus. The coordinates for bilateral electrolytic NB lesion were: 0.7 mm posterior ; 2.7 mm lateral and 8.0 mm ventral to the bregma. The site of the lesion was histologically verified. Fifteen days later the passive avoidance task according to the procedure of Ashford and Jones (1976) was performed. A. total of four consecutive daily sessions were given. The behavior of the NB lesioned rats under the influence of various drugs was measured. The control animals received 0.9% NaCl solution. Other rats received piracetam (100 mg/kg or 2 g/kg) or lecithin (250 mg/kg) or arecoline hydrochloride (1 mg/kg) or combinations of piracetam (100 mg/kg or 2 g/kg) + lecithin or piracetam (100 mg/kg or 2 g/kg) + arecoline. All the tested drugs were given intraperitoneally once per day. Arecoline was injected 10 minutes and lecithin or piracetam 1 hr before the passive avoidance experiment starting in the course of four behavior testing days. The results of our experiments show that piracetam (100 mg/kg) or lecithin or arecoline alone or in combination improved the passive avoidance in the NB lesioned rats. Piracetam (2 g/kg) alone was ineffective, but in combinations with mentioned cholinomimetics antagonized the cognitive deficits in the lesioned rats.

Alzheimer's disease (AD) is characterized by progresive loss of memory The cholinergic cells of the nucleus basalis of Meynert (NBM) have recently been found to degenerate in AD and are thought to be at least partly responsible for the cognitive deficits which are main characteristics of this disease. Intact cholinergic system is a prerequisite to unimpaired performance in learning and memory tasks. Because lesions of NBM reduce memory, it was of interest to study the effect of various cholinergics or nootropic drug-piracetam on the passive avoidance acquisition in the rat with bilateral electrolytic lesions of NBM equivalent. Drugs used were: lecithin (3, 2x10-4 mol/kg i.p.), arecoline (6, 4x10-6 mol/kg i.p.), piracetam (1, 4x10-2 mol/kg i.p.), piracetam (1, 4x10-2 mol/kg i.p.) + arecoline (6, 4x10-6 mol/kg i.p.) and piracetam (1, 4x10-2 mol/kg i.p.) + lecithin (3, 2x10-4 mol/kg i.p.). NBM lesions significantly impaired the passive avoidance acquisition related to the control group. The avoidance acquisition deficit was improved by arecoline or lecithin or by lecithin with piracetam or by arecoline with piracetam while piracetam alone didn't influence it significantly.

Intact cholinergic system is a prerequisite to unimpaired performance in learning and memory tasks. Bilateral electrolytic lesions of the nucleus basalis (NB) equivalent reduce the passive avoidance in the rat. The effect of intraperitoneally injected lecithin (3.2 x 10-4 mol.kg-1), arecoline (6.4 x 10-6 mol.kg-1), or piracetam (1.4 x 10-2 mol.kg-1) alone or in combination with before mentioned cholinomimetics on the passive avoidance in NB lesioned rats was examined. It was found that lecithin and arecoline alone or in combination with piracetam improved the avoidance acquisition in NB lesioned rats, while piracetam was uneffective.

Approximately 70% cholinergic projections of the frontoparietal neocortex is derived from ACh neurons in substantia innominata/nucl1eus basalis (SI/NB). The purpose of this study was to examine: 1) the influence of SI/NB lesion on the passive avoidance acquisition in the rat, and 2) if arecoline (1 mg/kg i.p.), physostigmine (0, 1 mg/kg i.p.) and lecithine (250 mg i.p.) may reverse the memory deficit of lesioned rats. Bilateral SI/NB lesion significantly impaired the passive avoidance acquisition related to the control group and sham lesioned rats. Acquisition was significantly improved in arecoline-treated rats, while physostigmine or lecithine didn't influence it significantly.

Alzheimer's disease is characterized clinically by cognitive deficits and histologically by a selective degeneration of neurons originating in the nucleus basalis of Maynert (NBM). The purpose of this study was to explore: 1. the influence of bilateral electrolytic lesions of NBM equivalent in rats on acquisition, and 2. if arecoline, THA, galantamine and physostigmine may influence acquisition in lesioned rats. NBM lesions significantly impaired the passive avoidance acquisition related to the control group. Acquisition was significantly improved in arecoline-treated rats, while AChE inhibitors didn't influence it significantly in experimental conditions used.

The frontal neocortex, the hippocampus and the cholinergic afferents to these areas have an important role in memory processes. The major cholinergic innervation for neocortical regions originates from the nucleus basalis magnocellularis (NB). Lesions of the NB are associated with an impairment of cognitive functions. Therefore we have analyzed the influence of various acetylcholinesterase inhibitors on the passive avoidance in rats with bilateral electrolytic lesions of mentioned structure. Wistar albino rats weighing 200-250 g were used. Bilateral electrolytic NB lesions were made by using the coordinates 0.7 mm posterior ; 2.7 mm lateral to the bregma, 7 mm below the dura. 15 days after the surgery the lesioned rats started the passive avoidance test per the procedure of Ashford and Jones, 1976. The control animals received 0.9% NaCl solution. Other NB lesioned rats received physostigmine salicylate ( 0, 001 ; 0, 01 ; 0, 1 mg/kg) ; galanthamine hydrobromide (0, 01 ; 0, 1 ; 1 mg/kg) or tetrahydroaminoacridine (THA) hydrochloride (0, 01 ; 0, 1 ; 1, 0 mg/kg ). All tested drugs were given intraperitoneally, once per day in the course of four testing days. Physostigmine was injected 1/2 and the other substances 1 hr before the passive avoidance experiment started. The results of our experiments show that mentioned acetylcholinesterase inhibitors in some tested doses can improve the passive avoidance in the NB lesioned rats.

It was of interest to study the influence of unilateral or bilateral electrolytic lesions of the NB on the passive avoidance behaviour in rats. Anesthetized male Wistar rats weighing 200-250 g (4-5 months old) or 350-480 g (more than 1 year old) were placed in a stereotaxic apparatus. The coordinates for unilateral or bilateral NB lesions for older animals were: 1.8 mm anterior ; 2.5 mm lateral and 8.0 mm ventral with bregma as 0. For younger rats the used coordinates were: 0.7 mm posterior ; 2.7 mm lateral and 8.0 mm ventral with bregma as 0. In sham lesioned rats the electrode was lowered into the NB, but without turning on the current. Fifteen day later passive avoidance task was performed. At the end of experiment the site of the lesion was histologically verified. Our results show that both unilateral and bilateral electrolytic lesions of the NB impaired the passive avoidance responses in young and old rats. Bilateral in comparison with unilateral NB lesion produced significantly higher avoidance deficit. These results suggest that the NB cells intact activity is a prerequisite to unimpaired performance in learning and memory tasks in young and old rats.

The purpose of this study was to examine the influence of impaired cholinergic function produced by the atropinisation or by bilateral electrolytic or neurotoxic lesions of the nucleus basalis magnocelluularis (NB) on the passive avoidance behavior in the rat. Namely, during the past decade numerous laboratories have implicated deficiencies in cholinergic function as contributing to the loss of memory in old age as well as the more severe cognitive disturbances occurring with Alzheimer's disease (AD). The degeneration of the cholinergic pathways innervating cortex and hippocampus appears to be the most important pathogenetic mechanism of the mental impairment characterizing the AD. The NB provides the primary cholinergic input to the cortical mantle. Lesions of the NB reduce cortical CAT and AChE activity, ACh release and choline uptake. The study was carried out on Wistar albino rats weighting 200-250 g. Atropine sulfate (6 mg/kg) was injected i.p. to intact animals half an hour before the passive avoidance test started. All the other animals were anesthetized and placed on a stereotaxic frame. Bilateral electrolytic NB lesions were made by using a direct current of 10 mA passed through a unipolar electrode for 10 sec. Bilateral neurotoxic lesions of the NB were made by application of 1.0 μg kainic acid in 1.0 μI sodium phosphate buffer. The coordinates for the lesion were 0.7 mm posterior ; 2.7 mm lateral and 8 mm ventral to the bregma. The sites of the .lesions were verified histologically after perfusion per the technique of Wolf (1971). After a 15 days lasting postoperative recovery period passed, each NB lesioned animal was subjected to the behavior test (the procedure of Ashford and Jones, 1976). The results of our experiments show that an impairment of the cholinergic function, either by the atropinisation or by the NB lesions, produced marked deficit in the passive avoidance behavior in rats.

The major source of extrinsic cholinergic innervation of the cerebral cortel in rats are magnocellular neurons of the basal forebrain, lying ventrally and medially to the globus pallidus. They are analogous to the nucleus basalis of Meynert (NB) in primates and their damage leads to the development of senescence related cognitive disorders similar to senile dementia of Alzheimer type in man. To establish the possible involvement of these structures in control of immune responsiveness, in this study we analysed the antibody and cell mediated immunity in rats subjected to bilateral electrolytic lesions of NB. For this purpose (A0xDA)F1 male rats aged 4 months were used. The coordinates for bilateral stereotaxic lesions were 1.8 mm anterior, 2.5 mm lateral to the bregma and 7 mm below the dura. Electrolysis was performed unipolary at the anode with 10 mA. In sham lesioned rats, the electrode was lowered into the NB, but without turning on the current. Ten days later these operated rats and a group of intact animals were sensitized with sheep red blood cells (SRBC) or transplanted with the skin of Y strain of rats. At the end of experiment the site of lesion was histologically verified. The results revealed that bilateral electrolytic lesions of NB did not influence significantly the generation of plaque forming cells in spleen, but produced an enhancement of graft survival. The result was highly significant versus intact control (15.8±0.4 and 12.8±0.5 days, respectively, p

A major source of extrinsic cholinergic innervation of the cerebral cortex in rats are magnocellular neurons of basal forebrain, lying ventrally and medially to globus pallidus. They are analogous to the nucleus basalis (NB) in primates, and their damage produces significant decreases of neocortical cholinergic markers and behavioral changes. Therefore the purpose of this study was to investigate the dose-response relationship between various doses of. Lecithin or arecoline and the passive avoidance behavior in the NB lesioned rats. The study was carried out on Wistar albino rats weighting 200-250g. Animals were anesthetized and bilateral electrolytic NB lesions were made. The coordinates for the lesions were 0.7 mm posterior ; 2.7 mm lateral and 8.0 mm ventral to the bregma, After a 15 days lasting postoperative recovery period passed, each the NB lesioned animals was subjected to the passive avoidance test (the procedure of Ashford and Jones, 1976). A total of four consecutive daily sessions were given. Drugs used were: 0.9% NaCl solution (control), arecoline hydrochloride (0, 01 mg/kg ; 0, 1 mg/kg ; 1 mg/kg) ; lecithin (2, 5 mg/kg ; 25 mg/kg ; 250 mg/kg). All the tested drugs were given intraperitoneally once per day. Arecoline was injected 10 minutes and lecithin one hour before the passive avoidance experiment starting in the course of four behavior testing days. The results of our experiments show that bilateral electrolytic lesions of the NB impaired the passive avoidance task in the rat. Arecoline and lecithin in some tested doses were effective in reversing the memory deficits in the NB lesioned rats.

The passive avoidance behaviour reduction was caused by bilateral electrolytic lesions of the nucleus basalis equivalent (NB) in rats. Intraperitoneal injection of cholinomimetics lecithin (3.2x10-4 mol.kg-1) and arecoline (6.4x10-6 mol.kg-1) significantly improved the passive avoidance in the NB lesioned rats. There is no significant difference between the effects of lecithin or arecoline or in combination.

Alzheimer's disease is characterized clinicaly by progresive loss of memory and histologically by a selective degeneration of cholinergic neurones originating in the nucleus basalis of Meynert. Approximately 70% of the cholinergic innervation to the frontoparietal neocortex is derived from mentioned structure (1). Intact cholinergic system is a prerequisite to unimpaired performance in learning and memory tasks. It was of interest to study the effect of various cholinergics on the passive avoidance acquisition in rats with bilateral electrolytic lesions of nucleus basalis equivalent. Drugs used (i.p.) were: lecithin, arecoline, THA, galantamine and physostigmine. Nucleus basalis equivalent electrolytic lesions significantly impaired the passive avoidance acquisition. The avoidance acquisition deficit was significantly improved in arecoline and lecithin treated rats, while AChE reversibile inhibitors didn't influence it significantly. (1) Johnston, M.V., McKinney, M., Coyle, J.T. (1979). Proc. Natl.Acad.Sci. , 76, 5392-5396.