Biomedical subjects
Publications and source records attributed to M Langmeier.
Implantation of an embryonal hippocampal tissue suspension into the area of the kainic acid lesion brought about an increase of the number of neurons. These neurons formed dendritic trees of an irregular pattern. Only neurons located within the pyramidal layer had the typical arrangement of pyramidal cells, but their dendrites were shorter and less branched.
The sensorymotor area of the cerebral cortex of the laboratory rat was repeatedly electrically stimulated after 10-minute intervals which led to progressive lengthening of the self-sustained after-discharges (SSAD). One minute, 10 minutes and one hour after completion of the third SSAD the authors examined by an electron microscope synapses type I according to Gray from the IInd cortical layer of the sensorymotor area of the contralateral hemisphere. One minute after termination of the fit a marked drop of the number of granular synaptic vesicles was noted in the immediate vicinity of the synaptic cleft, as well as in the whole synapsis, which correlates very closely with the reduced excitability of tissue during this period. Ten minutes after the end of the fit the number of vesicles rises markedly in both evaluated areas. This finding again corresponds well to the functional state, i.e. an increased excitability. One hour after the end of SSAD no changes in the number of vesicles near the synaptic cleft was found which might be associated with a greater functional capacity of the synaptic apparatuses. The results confirmed the idea on the synaptic apparatus as a structure which reflects from the morphological aspect very accurately changes of the functional state of the central nervous system.
An influence of ethosuximide on thalamically induced epileptic afterdischarges was studied in 47 rats aged 12 and 18 days. An afterdischarge formed by spike-and-wave rhythm was induced only in 18-day-old rats. It exhibited a tendency to progressive prolongation with repeated stimulations (with 15 min intervals). Ethosuximide in a dose of 125 mg/kg i.p. immediately after the first afterdischarge did not change the duration of subsequent afterdischarges. The second type of epileptic afterdischarge formed by spikes and/or serrated waves could be induced in both age groups studied. Ethosuximide even worsened the tendency to progression of epileptic afterdischarges in 12- as well as 18-day-old animals. Ethosuximide did not exhibit an anticonvulsant action against the spike-and-wave afterdischarge in 18-day-old rats. On the contrary, it aggravated the course of progressive changes with repeated stimulations in both age groups.
Excitatory synapses were studied in the hippocampal dentate gyrus ipsilateral to the stimulated entorhinal cortex in fully kindled rats 2 weeks after the last (3rd) stage 5 seizure. No change was observed in the absolute number of synaptic vesicles. On the other hand, marked redistribution of the vesicles in the synaptic apparatus was found, with a shift to a strategic position in the vicinity of the synaptic cleft. This redistribution evidently makes it possible to increase the supply of neurotransmitter needed for hyperfunction of the synaptic apparatus in kindling.
Interneuronal connections are an important component of the integration circuits of the hippocampus. They are formed mostly postnatally, i.e. in a phase when their development can be strongly influenced by external environmental factors. In model postnatal hypoxia, a morphometric analysis showed reduction of the number of dendritic segments (chiefly 3rd order segments) in 18-day-old rats. The total length of the dendrites was unaltered, but mean segment length increased. Interneuron density in the experimental animals was higher, especially in the stratum radiatum, but pyramidal cell density was lower than in the controls. These findings are evidence that hypoxia has a complex effect on the microstructure of the hippocampus and that, in the long run, it can lead to impairment of the balance of the elementary processes of excitation and inhibition.
Electrically evoked hippocampal afterdischarges are used as a model of partial epileptic seizures with a complex symptomatology and for testing anticonvulsants and toxic substances. Stimulating electrodes were implanted in the dorsal hippocampus of 16 laboratory rats and when the animals had recovered they were stimulated (15-s series, 8 Hz, pulse length 1 ms) with a voltage double the threshold value for a tissue response. The following features of the evoked afterdischarge were evaluated: the duration of the first phase of the afterdischarge, the duration of the non-active interphase, the duration of the second phase and the number of "wet dog shakes" (a constant accompaniment of hippocampal afterdischarges). Localization of the electrodes in the CA1 (n = 7) and CA3 (n = 7) region of the hippocampus made no difference to these parameters and in both cases the measured and evaluated data were the same. The afterdischarges were always accompanied by a marked orientation reaction. The study showed that when using macroelectrodes to stimulate the dorsal hippocampus, their localization in the CA1/CA3 is not of critical importance.
Structural parameters of neuronal circuits were studied in rats exposed to aerogenic hypoxia during the postnatal development. In 18-day-old experimental animals pyramidal cells of the hippocampal CA1 area had less branches of the apical dendrites. These branches were shorter with lower dendritic spine density. Myelinated axons in the corpus callosum were less frequent. In electron-microscopic picture the mean section area of myelinated axons was lower, the myelin sheets were thinner and consisted of less myelin layers. Synapses in the II. layer of the somatosensoric cortex had more often flat pre-synaptic dense projections, smaller width between pre- and post-synaptic densities and thinner post-synaptic densities.
Infant rats, together with the female, were exposed to a simulated altitude of 7,000 m every day from birth to the age of 17 days, excepting the 6th, 7th, 13th and 14th day. Animals were studied on the 18th day, 20 hours after the last exposure to hypoxia. Rats aged 12, 15 and 18 days acted as the controls. The number of myelinated axones of the corpus callosum rose from the 12th to the 18th day; the number in animals exposed to hypoxia did not differ significantly from the number in the 15-day-old controls. Axonal section area likewise increased from the 12th to the 18th day and again the value in animals exposed to hypoxia was no different from section area in 15-day-old animals. The number of myelin lamellae rose from the 12th to the 18th day, but in animals exposed to hypoxia it did not differ significantly from the value found in 12-day-old animals. The thickness of the myelin layer increased from the 12th to the 18th day; in the experimental animals it was the same as in the 12-day-old controls. The myelin lamellae likewise became thicker, between the 12th and the 15th day; in animals exposed to hypoxia this parameter was the same as the value in 12-day-old rats. In the electrophysiological part of the study, the development of the interhemispheric response was analysed. In animals exposed to hypoxia, the individual waves of the IHR had the same shape and latent periods as in 15-day-old animals. The results demonstrate that hypoxia has a profound effect on morphological and functional maturation of the corpus callosum in infant rats.
The sensorimotor area of rat cerebral cortex was subjected to repeated electrical stimulation at 10-min intervals, with resultant formation and progressive lengthening of self-sustained after-discharges (SSAD). One and 60 min after the third SSAD ended, we carried out an electron microscopy morphometric analysis of the agranular synaptic vesicles in type I synapses (after Gray) in the second cortical layer of the homotopic area of the unstimulated hemisphere. One minute after the seizure ended, 5.8% enlargement of the synaptic vesicles compared with the control was demonstrated in zone II of the synapse (0.1-0.2 micron from the active zone of the synapse). Neither the size nor the shape of the synaptic vesicles in the other parts of the synaptic apparatus altered. Sixty min after the seizure ended, a 5.5% enlargement of the synaptic vesicles in zone I (0.0-0.1 micron) and a 5.4% enlargement of those in zone II was found. The synaptic vesicles in zone I in the experimental animals were more oval than in the controls. Our findings support the vesicular theory and testify that hyperfunction, up to temporary exhaustion of the synaptic apparatuses, produces a change in the transmitter content of the synaptic vesicles. A raised amount of transmitter in the synaptic vesicles near the active zone could be one of the factors responsible for continued hyperexcitability of the tissue one hour after the seizure had ended. The results likewise support the concept of two mechanisms of synaptic vesicle formation, and hence of the existence of two different vesicle populations.
Among the experimental models of epileptic seizures there is a lack of an adequate model of partial seizures with complex symptomatology. This is due to the fact that the disturbance of consciousness is the main symptom of this type of human seizures, whereas motor signs appear only as epileptic automatisms. Therefore, experimental epileptology focuses its attention on electrophysiological phenomena connected with these fits. The commonly used model is an after-discharge (AD), induced by electrical stimulation of the hippocampus. Its electrographic pattern resembles phenomena recorded by means of deep electrodes in human temporal seizures (Kreindler 1965).
Repeated electrical stimulation of the sensorimotor area in the rat cerebral cortex at 10-min intervals led to the formation and progressive lengthening of self-sustained after-discharges [SSAD]. One hour after the third SSAD ended, we evaluated the number of synaptic vesicles in type I synapses according to Gray in the second cortical layer of the homotopical part of the unstimulated hemisphere in the vicinity of the active synaptic zone and the total number of vesicles in sections of the presynaptic bag. We also made a semiquantitative evaluation of exocytotic and endocytotic activity on the presynaptic membrane. No statistically significant differences between the experimental and the control animals were demonstrated in any of the ultrastructural parameters studied. Persistent hyperexcitability of the tissues one hour after the SSAD ended was evidently due to other synaptic transmission mechanisms, which cannot be detected by morphological methods.
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Repeated electrical stimulation of the sensorimotor region of rat cerebral cortex at 10 min intervals led to the development and progressive prolongation of self-sustained after-discharges (SSAD). One minute after the third SSAD ended, an electronoptic morphological analysis of type I synapses after Gray from the second cortical layer of the homotopic area of the unstimulated hemisphere was carried out. In the experimental animals, an 11.7% increase in the area of the presynaptic bag and a 5.5% increase in its perimeter were demonstrated. The number of agranular synaptic vesicles per constant unit area fell by 70.8%. The area of the mitochondria in the presynaptic ending increased by 49.8% and their perimeter by 16.1%. The area of the postsynaptic element increased by 34.1% and its perimeter by 15.7%. Changes in the synapses are evaluated as manifestations of exhaustion and primarily as a manifestation of ion shifts during the epileptic seizure. The findings nevertheless also testify to incipient activation of restitution mechanisms in the structures of the synaptic apparatus within a very short time after termination of the seizure.
The sensorimotor area of rat cerebral cortex was subjected to repetitive electrical stimulation at 10-min intervals; this led to progressive lengthening of self-sustained afterdischarges (SSADs). At 50-60 s after cessation of the third SSAD the brains of the animals were perfused transaortally with fixing fluid, and a quantitative electron microscopic analysis of type I synapses in the second cortical layer of the sensorimotor area of the contralateral hemisphere was carried out. In a zone 0.1 micron wide adjacent to the presynaptic membrane in the active zone, the number of synaptic vesicles (converted to the number per 0.01 micron2 area) in the experimental animals fell by 64.6%. In a zone of the same width 0.1 micron distant from the presynaptic membrane, it fell by 67.6%. The mean absolute synaptic vesicle count per presynaptic bag section fell by 66.6%. The number of synapses showing signs of exocytosis rose in the experimental animals from 3.8 to 5.9%, while the number with clearly demonstrable exocytosis rose from 0.7 to 11.4%. The proportion of synapses with signs of (clearly demonstrable) endocytosis rose from 2.8% (2.1%) in the controls to 7.1% (3.7%) in the experimental rats. In the experimental and control animals we demonstrated complex vesicle formation in 4.3 and 3.8%, respectively, of the synapses and dense-cored vesicles in 7.7 and 2.8%, respectively, of the synapses. We consider changes in the number and formation of synaptic vesicles to be signs of exhaustion of the synapses caused by the previous epileptic seizure, which simultaneously activates mechanisms of vesicle formation.
Repeated electrical stimulation of the sensorimotor region of the rat cerebral cortex at 10-min intervals led to progressive lengthening of the self-sustained after-discharges (SSAD). 50-60 s after termination of the third SSAD we examined, in the electron microscope, type I synapses (after Gray) in the second cortical layer of the sensorimotor region of the contralateral hemisphere. In the experimental animals we demonstrated swelling of both the pre- and post-synaptic elements, a decrease in the number of agranular synaptic vesicles and variability of their shape and size. Frequent manifestations of exo- and endocytic activity and a frequent incidence of complex vesicles have been described. Saccular dilatation of the space between the outer and inner mitochondrial membrane in the presynaptic terminal and dilatation of the terminal cisternae and extracellular space occurred. Alteration of the spine apparatus was observed in the postsynaptic elements. At the margin of the active zone we described simultaneous invagination of the pre- and postsynaptic membrane up to the formation of rounded structures with two concentric membranes. The changes in the synapses are conceived as signs of exhaustion due to the previous epileptic seizure, which on the other hand, activated the restitution mechanisms of the structure of the synaptic apparatus.
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The sensorimotor area of the cerebral cortex of rats was repetitively electrically stimulated (8 Hz for sec) at 10-min intervals, inducing a gradual prolongation of self-sustained after-discharges (SSADs). At 10 min after termination of the third SSAD, the animals were perfused with a fixation solution. The homotopic area of the contralateral hemisphere was examined in the electron microscope. In the II cortical layer, the agranular synaptic vesicles in type I synapses (after Gray) were counted close to the synaptic cleft. The number of synaptic vesicles was significantly increased in the experimental animals.
A projected epileptic focus was induced in the brains of experimental rats by applying penicillin G sodium to the contralateral hemisphere. Synapses of type I (after Gray) in the second cortical layer of the mirror area were analyzed morphometrically in the electron microscope 30 min after application of the epileptogenic drug. The number of agranular synaptic vesicles was counted per 0.01 micron2 over the active zone of the presynaptic membrane in an area 0.1 micron wide adjacent to the active zone and in an area of the same width 0.1 micron distant from the active zone. A statistically significant increase in the number of synaptic vesicles was found in the experimental animals as compared with the controls. The number of synaptic vesicles per 0.01 micron2 area was evaluated along the inactive presynaptic membrane, both in the area adjacent to the active zone of the presynaptic membrane and in other areas at successively greater distances from the active zone. The counts in some of these latter areas were statistically significantly higher in the experimental animals. The size and shape of synaptic vesicles were evaluated in three zones, each 0.1 micron wide, parallel to the membrane of the synaptic cleft. Zone I was directly adjacent to the membrane of the synaptic cleft; zone II was 0.1 micron distant; and zone III 0.1 micron distant from the membrane. The results show that the synaptic vesicles of both the experimental and control animals are significantly smaller in zone I than in the more distant zones. This trend is more marked in the controls than in the experimental animals. Histograms of vesical areas of zones II and III in the controls point to two populations of vesicles. The volumes of vesicles are approximately 10% greater in zone I of experimental animals than in the controls. The elongation of the vesicles in the three zones does not differ statistically either in controls or in experimental animals. Experimental animals, however, have statistically more rounded vesicles than the controls. Assuming that the synpatic vesicles contain the transmitters, our results might contribute to a better understanding of the increased excitability of the epileptic focus area.