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PubMed1990

Astrocytosis in the molecular layer of the dentate gyrus: a study in Alzheimer's disease and schizophrenia.

Recently, several authors have claimed prominent abnormalities in the entorhinal cortex of both patients with Alzheimer's disease (AD) and schizophrenia. The entorhinal cortex is the origin of the perforant pathway, a major input to granule cells of the dentate gyrus of the hippocampus. The present study explored the possibility of a lesion in the entorhinal cortex of both AD and schizophrenic patients by quantitating astrocytic markers within the terminal fields of the perforant pathway. An increase in fibrillary astrocytes was found in half (3/6) of the AD patients while none of the schizophrenic (n = 6) or control (n = 7) brains exhibited gliosis. Since the redistribution and hyperplasia of astrocytes within the molecular layer of the partially deafferented dentate gyrus depend on the chronicity of the entorhinal lesion, the abnormalities observed in AD patients are consistent with the progressive course of the illness. Furthermore, the presence of gliosis in the subiculum of three out of six AD patients suggested pathology secondary to projections from the entorhinal region, amygdala, or prepyriform cortex. The absence of similar changes in schizophrenic patients does not disprove previous claims of entorhinal pathology but suggests that the lesion, if it exists, is either static in nature or occurred long before death.

Adult↗
PubMed1996

The alvear pathway of the rat hippocampus.

Neurons of the entorhinal cortex project to the hippocampus proper and dentate gyrus. This projection is called the "perforant pathway" because it perforates the subiculum; current usage applies this term to all entorhino-hippocampal fibers. However, entorhinal fibers also reach Ammon's horn via the alveus ("alvear pathway"), an alternative route first described by Cajal. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHAL) was used in order to analyze the contribution of this pathway to the temporo-ammonic projection. In the temporal portion of the rat hippocampus, most of the entorhinal fibers reach Ammon's horn after perforating the subiculum (classical perforant pathway). At more septal levels, the number of entorhinal fibers that take the alvear pathway increases; in the septal portion of the hippocampal formation, most of the entorhinal fibers to hippocampal subfield CA1 reach this subfield via the alveus. These fibers make sharp right-angle turns in the alveus, perforate the pyramidal cell layer, and finally terminate in the stratum lacunosum-moleculare. The crossed temporo-ammonic fibers reach their termination area in the stratum lacunosum-moleculare of CA1 almost exclusively via the alveus. These data indicate that the alveus is a major route by which entorhinal fibers reach their targets in CA1.

Animals↗
PubMed2000

Lack of expression of long-term potentiation in the dentate gyrus but not in the CA1 region of the hippocampus of mu-opioid receptor-deficient mice.

The possible involvement of the mu-opioid receptor subtype in mechanisms of long-term potentiation (LTP) of the lateral perforant pathway to the dentate gyrus neurons, as well as of the Schaffer collateral-commissural input of CA1 neurons, was investigated using mu-opioid receptor-deficient mutant mice. In transversal hippocampal slices from mice lacking the mu-opioid receptor (MOR) only a short potentiation in the dentate gyrus after tetanization of the lateral perforant pathway was found. In contrast, the loss of the mu-opioid receptor in the CA1 region did not affect the potentiation of the field potentials induced by tetanization of the Schaffer collaterals. In parallel experiments, the application of 10 microM of the selective MOR-antagonist, funaltrexamine, decreased LTP in the dentate gyrus of wild-type mice but again did not alter the potentiation of the field potentials in the CA1. The loss of MOR-binding in the hippocampus was accompanied by a reduction in D2-binding sites indicating a possible compensatory role of the dopaminergic system. The D1- and glutamate binding was not affected. These observations confirm earlier results with pharmacological blockade of opioid receptors in the dentate gyrus and demonstrate an essential role of MOR activation for the generation of LTP in the dentate gyrus of the mouse but not necessarily in the CA1 region.

Action Potentials↗
PubMed1985

Action of norepinephrine in the dentate gyrus. I. Stimulation of locus coeruleus.

The effect of stimulating locus coeruleus (LC) on the response of dentate gyrus granule cells to medial perforant pathway stimulation was studied in anesthetized rats. Field responses were recorded simultaneously at the mid-dendritic and granule cell levels. Two types of responses were recorded: those due to the synchronous firing of granule cell action potentials (population spikes) and those produced by excitatory synaptic activity (evoked synaptic potentials or ESPs). Stimulation of LC prior to stimulating the perforant pathway resulted in a decrease in the ESP (inward current) measured at the dendrites and, in most animals, an increase of the population spike measured at the granule cell level. Although LC stimulation decreased the ESP at the dendrites, the ESP at the granule cell body level (outward current) was not affected. The changes in granule cell responses following LC stimulation are discussed in relation to previous findings in freely moving rats.

Animals↗
PubMed1995

The N-methyl-D-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias.

Phencyclidine (PCP) and ketamine can induce a model psychosis in drug addicts and exacerbate the symptoms of chronic schizophrenics. The model psychoses these drugs induce mimic a variety of schizophrenic symptoms, including flattened affect, dissociative thought disorder, depersonalization and catatonic states. These symptoms can persist for prolonged periods and chronic PCP and ketamine addicts have persisting memory deficits. Dizocilpine (MK-801) is a simpler drug than PCP or ketamine in its actions, but it shares with both the property of blocking in a non-competitive manner the N-methyl-D-aspartate (NMDA) ion-channel. Behavioral observations and drug-discrimination studies in animals indicate that PCP and dizocilpine are similar in their effects and they both have a neurotoxic effect on neurons in posterior cingulate cortex. Recent studies have indicated that both of these drugs, when given continuously for several days, further induce neuronal degeneration in other limbic structures. These include brain regions of rats related to olfaction, associated limbic structures such as piriform cortex and posterior regions of entorhinal cortex and in it's projections, through the perforant pathway, to dentate gyrus and other cells in ventral hippocampus. These degenerative consequences may be excitatory neurotoxic effects, for these compounds also induce an elevation in glucose metabolism maximal in just those structures where degeneration is observed and the degeneration involves entire cells, with all of their processes. It has been suggested these non-competitive NMDA antagonists induce an increase in firing rate in a limbic circuit which includes the perforant pathway. At least some competitive NMDA antagonists induce the same pattern of degeneration and altered glucose utilization. There is anatomical and functional evidence that alterations in these same limbic structures are present in the dementia syndrome manifested by some schizophrenics and most Alzheimer's patients. This suggests that these non-competitive NMDA antagonists may provide a more complete model of psychoses and memory disturbances than previously recognized, in that they can mimic both persisting symptomatology and neuroanatomical abnormalities. While the neurochemical underpinnings of this effect remain elusive, it appears to be both age and sex dependent. Further studies of the mechanisms by which NMDA antagonists induce increased glucose utilization and neurotoxicity in these limbic structures may clarify these alterations in this simplified Papez-like circuit.

Animals↗
PubMed1991

Propofol modification of evoked hippocampal dentate inhibition in urethane-anesthetized rats.

To learn more about the site and mode of action of propofol, the authors anesthetized rats with urethane, and implanted a stimulating electrode in the perforant pathway and a recording electrode in the hippocampal dentate gyrus to measure evoked field responses. Catheters were placed in the jugular vein and carotid artery to measure blood pressure, take blood samples for measurement of blood gases, and inject drugs. Rat lungs were ventilated, and increasing doses of propofol or its 10% fat emulsion vehicle were administered. Over a dose range of 2.5-40 mg/kg, propofol had little effect on the field excitatory postsynaptic potential (EPSP) or the field population spike (PS), suggesting no important actions on perforant pathway fibers or intrinsic granule cell excitability. With the use of various paired-pulse stimulation paradigms, it was demonstrated that propofol administration led to a dramatic decrease in granule cell excitability over interpulse intervals of 10-100 ms. The magnitude of this effect clearly was related to dose, and the effect was reversible with discontinuance of drug. The vehicle had marginal effects on granule cell excitability. These were significantly less than those produced by propofol. Transient reductions in blood pressure followed by transient increases to above baseline were observed after administration of propofol at most doses. Increased heart rates accompanied the slight increase in blood pressure. Except at the largest dose of propofol tested, cardiovascular measures had returned to near control levels by 8 min, when the evoked potentials were evaluated. Arterial blood gases showed little change throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗
PubMed1990

The pattern of GAP-43 immunostaining changes in the rat hippocampal formation during reactive synaptogenesis.

The reactive synaptogenesis that takes place in the rat hippocampal formation after certain experimental manipulations affords an opportunity to investigate the molecular events that underlie structural remodeling in the adult CNS. Between 2 and 4 days after lesioning the perforant pathway, levels of the synaptic phosphoprotein, GAP-43 (B50, F1, pp46, neuromodulin), were found to increase markedly in the inner molecular layer (iml) of the dentate gyrus, coincident with the time at which commissural-associational (CA) fibers begin to sprout axon collaterals into dendritic portions denervated by the lesion. GAP-43 immunostaining in the iml began to decline by 8 days but continued to define an expanded CA projection for at least one month. In the outer molecular layer (oml), GAP-43 levels decreased after the loss of perforant pathway terminals and did not return for 2-3 weeks, the time at which sprouting of septal inputs into this layer can be visualized by cholinesterase histochemistry. These results demonstrate that GAP-43 levels change during reactive synaptogenesis, and point to differences among neural systems in their expression of this protein.

Animals↗
PubMed2002

Interstitial cells subjacent to the entorhinal region expressing somatostatin-28 immunoreactivity are susceptible to development of Alzheimer's disease-related cytoskeletal changes.

Interstitial cells are isolated neurons located in the infracortical white matter that are known to express neuropeptides. Twenty-four cases selected for the absence, slight (Braak stages I-II), moderate (Braak stages III-IV), or serious degree (Braak stages V-VI) of cortical neurofibrillary pathology were studied for the presence of Alzheimer's disease-related abnormal tau in interstitial cells of the entorhinal region. AT8-immunoreactive white matter neurons were observed in all Braak stages of cortical neurofibrillary pathology. Both normal-appearing neurons and neurons with degenerative changes in the cellular processes were observed. Normal-appearing cells were predominantly found in stages I and II, whereas degenerative interstitial cells numerically increased from stage I onwards. The normal-appearing cells were medium-sized (10-25 micro m), with ovoid, fusiform, triangular or multipolar cell bodies, and showed an extensive dendritic field, which was oriented perpendicular to the direction of the perforant pathway. Since the morphology of the AT8-immunopositive normal-appearing cells was similar to that reported on somatostatinergic interstitial cells subjacent to the entorhinal region, double-labeling with AT8 and anti-somatostatin-28 (S309) was performed. All AT8-immunoreactive normal-appearing interstitial cells revealed co-staining with somatostatin-28 antiserum, whereas some of the AT8-immunopositive cells with degenerative processes reacted positively and others negatively with S309. In summary, a distinctive interstitial cell type characterized by extensive arborization oriented perpendicular to the course of the perforant pathway and showing somatostatin expression is susceptible to developing the Alzheimer's disease-related cytoskeletal changes. Progression in cytoskeleton change is accompanied by loss of somatostatin.

Adult↗
PubMed1991

Senile dementia of the Alzheimer type: is there a correlation between entorhinal cortex and dentate gyrus lesions?

Senile plaques (SP) are one of the neuropathological hallmarks of senile dementia of the Alzheimer type (SDAT). In 14 patients affected with SDAT (over 74 years of age), thioflavine S, Tau and acetylcholinesterase (AChE) stainings demonstrated an increased density of SP in the outer two thirds of the dentate gyrus molecular layer. However, a wide range of SP density was observed among the cases. The molecular layer of the dentate gyrus is one of the termination site of the perforant pathway that originates in layers II and III of the entorhinal cortex. We have found that the number of AChE-, thioflavine S- and Tau-positive SP that accumulate in the dentate gyrus is positively correlated with the density of thioflavine S-stained neurofibrillary tangles in layers II and III of the entorhinal cortex. In contrast, a similar correlation is not found when using Tau immunolabeling of the entorhinal tangles. These observations show an association between the accumulation of AChE-positive SP in the dentate molecular layer and the lesions of the perforant pathway. Furthermore, they suggest that the density of SP in the dentate gyrus correlates with the late stages of neurofibrillary tangles formation (thioflavine S positive), but not with the early stages (Tau positive).

Acetylcholinesterase↗
PubMed1999

Neonatal stress alters LTP in freely moving male and female adult rats.

We previously reported that neonatal isolation stress significantly changes measures of hippocampal long-term potentiation (LTP) in male and female juvenile rats, i.e., at 30 days of age. The changes in dentate granule population measures, i.e., excitatory postsynaptic potential (EPSP) and population spike amplitude (PSA), evoked by tetanization of the medial perforant pathway, indicated that juvenile rats exposed to neonatal isolation exhibit different enhancement profiles with respect to both the magnitude and duration of LTP in a sex-specific manner. Isolated males showed a significantly greater enhancement of LTP, while female "isolates" showed significantly longer LTP duration when compared to all other groups. The present study was designed to determine whether the effects of the neonatal isolation stress paradigm endures into adulthood. Rats isolated from their mothers for 1 h per day during postnatal days 2-9 were surgically prepared at 70-90 days of age, with stimulating and recording electrodes placed in the medial perforant pathway and the hippocampal dentate gyrus, respectively. Prior to tetanization, no significant effect of sex or treatment was obtained for baseline measures of EPSP slope or PSA. In order to rule out baseline differences in hippocampal cell excitability in female adult rats, we measured the response of dentate granule cells for one estrus cycle and found no pretetanization enhancement in the evoked response in either controls or previously stressed rats. Following tetanization, there was a significant treatment and sex effect. During the induction of LTP, PSA values were significantly enhanced in both isolated males and females and had significantly longer LTP duration when compared to the unhandled control group. Additionally, we observed that females took longer to reach baseline levels than males. Taken together, these results indicate that repeated infant isolation stress enhances LTP induction and duration in both males and females. These results indicate that infant stress alters hippocampal neuroplasticity in such a way that its effect endures into adulthood.

Age Factors↗
PubMed1988

Sensory modulation of hippocampal transmission. I. Opposite effects on CA1 and dentate gyrus synapsis.

Neuronal transmission through hippocampal subfields exhibits a high degree of modulation and appears dependent on the behavioral state and hippocampal EEG. Sensory inputs, which profoundly modify the hippocampal EEG, may be involved in modulating hippocampal excitability. Field responses of the CA1 region, evoked by ipsilateral CA3 or perforant path stimulation, as well as dentate gyrus potentials evoked by perforant path stimulation were recorded in paralyzed and locally anesthetized rats and studied before, during and after sensory stimulation, consisting of gentle stroking of the animal's fur. On some occasions the CA1 was also antidromically driven from the posterior alveus in order to study the recurrent inhibitory loop and paired pulses were applied to the perforant pathway to study recurrent inhibition in the dentate gyrus. Evoked responses were averaged and field excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude measured. In addition the positive wave which follows the population spike, which corresponds in part to the recurrent IPSP, was also evaluated. Sensory stimulation, which evoked a high-amplitude 5-6 Hz theta (theta)-rhythm in the hippocampal EEG, drastically depressed the efficacy of Schaffer collateral volleys in discharging the CA1 cells. The EPSP-PS curves, however, were not altered revealing that cellular excitability was unaffected. The inhibitory CA1 loop appeared to be unaltered. In contrast, the dentate gyrus responses to perforant pathway stimulation were enhanced during periods of sensory stimulation and the cellular excitability increased, as judged by the shift to the left of EPSP-PS relation. In addition, the recurrent inhibition appeared to be reduced during sensory stimulation. Present results demonstrate that sensory stimulation causes modulation of information transfer through the hippocampus. This modification of hippocampal transmission may serve to properly gate the information reaching the CA1 and dentate gyrus.

Action Potentials↗
PubMed1989

Myelination of cortical-hippocampal relays during late adolescence.

The normal developmental series of brains in the Yakovlev Collection has been examined to explore the possibility that various brain regions implicated in schizophrenia may show changes in myelination during late adolescence, a period coinciding with the appearance of early symptoms of this disorder. The prefrontal, cingulate, and parahippocampal (entorhinal) cortex, as well as the perforant pathway, cingulum bundle, and hippocampus, were closely examined because these regions have recently been found to show various neuropathological differences in schizophrenia. Observation of these specimens has confirmed earlier reports by Yakovlev and Lecours (1967) that primary motor and sensory cortices show robust myelination early in the first decade of life. In contrast, associative cortical areas show increased amounts of myelin staining only by the second decade, although some cortical areas, like the cingulate and basofrontal cortex, remain poorly myelinated throughout life. The most striking finding, however, was the appearance of increased myelination of the subicular and presubicular regions during the late adolescent period. Increased myelination in the subiculum was localized to a discrete region at the surface where fibers of the perforant pathway are known to aggregate as they course toward the area dentata. The comparable region in the adjacent presubicular area that also showed increased myelin staining probably contains distal portions of the cingulum bundle. Support for this latter possibility was obtained from a single case in which a stereotaxically placed lesion causing interruption of the cingulum bundle showed less myelin in the presubicular area of the effectively lesioned side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1996

Status epilepticus causes selective regional damage and loss of GABAergic neurons in the rat amygdaloid complex.

In human epilepsy, the amygdala is often a primary focus for seizures. To analyse the status epilepticus-induced alterations in the amygdaloid circuitries which may later underlie epileptogenesis, we studied the amygdaloid damage in kainic acid and perforant pathway stimulation models of status epilepticus in the rat. We also studied the damage to inhibitory GABAergic neurons. In both models, the medial division of the lateral nucleus, the parvicellular division of the basal nucleus and portions of the anterior cortical and medical nuclei were damaged. In the kainate model, where the seizure activity was more severe, the accessory basal nucleus, amygdalohippocampal area, posterior cortical nucleus and periamygdaloid cortex were also damaged. Two weeks after kainate-induced seizures, 56% of the GABA-immunoreactive neurons remained in the lateral nucleus (P < 0.05) and 25% in the basal nucleus (P < 0.01). Further analysis showed that one subpopulation of damaged GABAergic neurons was immunoreactive for somatostatin (48% remaining in the lateral nucleus, P < 0.01; 33% in the basal nucleus, P < 0.01). In the perforant pathway stimulation model, the damage to somatostatin neurons was milder. According to our data, the initial insult, such as status epilepticus, selectively damages amygdaloid nuclei. The loss of inhibition may underlie the spontaneous generation of seizures and epileptogenesis. On the other hand, many amygdaloid output nuclei (magnocellular and intermediate division of the basal nucleus, the central nucleus) remained relatively undamaged, providing pathways for seizures spread and generation of seizure-related behavioural manifestations such as motor convulsions and fear response.

Amygdala↗
PubMedDate not supplied

Synaptophysin immunoreactivity in Pick's disease: comparison with Alzheimer's disease and dementia with Lewy bodies.

Frontotemporal lobe atrophy is a hallmark of Pick's disease (PiD), however, the underlying pathobiology of the neuronal losses is unknown. Synaptic losses have been described in Alzheimer's disease (AD) and correlate with the severity of dementia, however few studies of synaptic integrity have been done to determine whether synaptic loss also contributes to symptoms in non-AD dementias. To begin to assess synaptic integrity in other types of dementia, we examined the site of termination of the hippocampal perforant pathway, the major source of afferent tracts to the hippocampus. We determined immunoreactivity for the synaptic-terminal specific protein synaptophysin in the outer molecular layer of the hippocampal dentate gyrus (OMDG) in eight PiD, nine AD, nine dementia with Lewy bodies (DLB), and seven control cases. Quantitative data were obtained using an Image-Pro automated image analysis system. In AD and PiD, synaptophysin immunoreactivity was visibly reduced in the OMDG Densitometric analysis confirmed that there were statistically significant differences among groups in synaptophysin immunoreactivity when comparing the OMDG to the adjacent inner molecular layer of the hippocampal dentate gyrus (IMDG) (p = 0.002). These differences were present between PiD and both the control and DLB groups. The AD group also showed a reduction in synaptophysin immunoreactivity compared with DLB and control groups. In contrast, perforant pathway synaptic losses in DLB were minimal. Our data supports the hypothesis that focal synaptic losses occur in PiD and AD and may contribute to the cognitive deficits in both conditions.

Aged↗
PubMed1997

Seizure-induced damage to somatostatin-immunoreactive neurons in the rat hippocampus is regulated by fimbria-fornix transection.

In both experimental and human temporal lobe epilepsy, seizures cause loss of hilar somatostatin-immunoreactive (SOM-ir) neurons and sprouting of mossy fibers. To investigate whether in rats these alterations are modulated by hippocampal input projections, we transected the fimbria-fornix or the perforant pathway bilaterally 2 days after seizures induced by systemic administration of kainic acid (9 mg/kg, i.p.). Two months later, the number of SOM-ir neurons in the hilus was counted and mossy fiber sprouting in the supragranular area and in the inner molecular layer was analyzed. In seizured rats with sham-operation, 50% of the hilar SOM-ir neurons were left in the septal end of the hippocampus and only 16% remained in the temporal end. In seizured rats with transection of the fimbria-fornix, the number of hilar SOM-ir neurons in the septal end of the hippocampus did not differ from that in controls (98% of SOM-ir neurons left). However, the temporal end was severely damaged (41% of SOM-ir neurons left). In seizured rats with transection of the perforant pathway, 61% of the hilar SOM-ir neurons were left in the septal end and 51% in the temporal end of the hippocampus. Mossy fiber sprouting was evident throughout the septotemporal axis of the hippocampus in all seizured rats. Our results suggest that in the septal end of the hippocampus the severity of neuronal damage in the hilus is modulated by mechanism(s) that are dependent on the afferent pathways entering the hippocampus via the fimbria-fornix. Transection of the fimbria-fornix, however, does not significantly modulate the severity or the target regions of seizure-induced sprouting of mossy fibers.

Animals↗
PubMed1996

Failure of carbamazepine to prevent behavioural and histopathological sequels of experimentally induced status epilepticus.

Sustained electrical stimulation of the perforant pathway was used to induce long-lasting hippocampal seizures in conscious rats. One hour prior to stimulation, rats were given i.p. injections of either saline or a commonly used antiepileptic drug, carbamazepine (5H-dibenz[b, f]azepine-5-carboxamide; CBZ; 20 mg/kg). When tested 2 weeks later in a water maze, both the saline- and the carbamazepine-pretreated rats showed similarly a severe impairment in spatial learning compared to non-stimulated controls. Histological evaluation revealed that the pyramidal cell damage was (P < 0.05) milder in the carbamazepine-pretreated group in the CA1, but not the CA3c subfield. However, the number of somatostatin-immunoreactive neurons in both stimulated groups was reduced equally. Thus, at the dose of 20 mg/kg, which is a usual anticonvulsive dose in humans, carbamazepine seems to offer only partial protection against pyramidal cell damage, but no protection against the hilar somatostatin-immunoreactive neuron loss or the spatial learning deficit after perforant pathway stimulation in rats. The result clearly differs from that obtained either with a GABA (gamma-aminobutyric acid)-enhancing drug and a novel antiepileptic, vigabatrin (4-amino-hex-5-enoic acid) or with a competitive NMDA (N-methyl-D-aspartate) receptor antagonist, CGP 39551 (DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid carboxyethylester) in the same test situation.

Animals↗
PubMed1989

Hippocampal damage induced by ischemia and intra-amygdaloid kainate injection: effect on N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites.

The N-methyl-D-aspartate receptor channel-complex is widely distributed in the hippocampus, particularly in the CA1 region, in the terminal field of CA3 pyramidal axons and in the fascia dentata, in the terminal field of the perforant pathway. In the present study, we have examined, in the rat, the effect of specific lesions of various neuronal populations of the hippocampus on the distribution of several markers of the N-methyl-D-aspartate receptor-channel complex. Anoxic-ischemic treatment produced a destruction of CA1 pyramidal cells (postsynaptic element): this was associated with a 50% loss of N-methyl-D-aspartate, glycine and N-(1-phenylcyclohexyl)piperidine binding sites. In contrast, the destruction of CA3 pyramidal cells and their axons (presynaptic element) by kainate treatment did not induce significant changes in the density of binding sites. The present results therefore strongly support an exclusively postsynaptic localization of the N-methyl-D-aspartate receptor-channel complex in CA1; the possibility of a localization of the remaining binding sites on glial cells or interneurons is discussed. In the molecular layer of the fascia dentata, the anoxic-ischemic treatment produced a partial destruction of the median perforant pathway (presynaptic element) associated with a decrease in the density of N-methyl-D-aspartate, N-(1-[2-thienyl]cyclohexyl)piperidine and glycine binding sites; this suggests that, in contrast to CA1, in the molecular layer of the fascia dentata, N-methyl-D-aspartate receptor-binding sites are located both pre- and postsynaptically.

Amygdala↗
PubMed1996

Vigabatrin and carbamazepine have different efficacies in the prevention of status epilepticus induced neuronal damage in the hippocampus and amygdala.

The present study compares the efficacy of carbamazepine (20 mg/kg/day) and vigabatrin (250 mg/kg/day) in preventing hippocampal and amygdaloid damage in the perforant pathway stimulation model of status epilepticus in the rat. One group of rats received a combination of the drugs. Drug treatments were started one week before the stimulation and continued for two weeks thereafter. Gallyas silver impregnation and somatostatin immunohistochemistry were used to detect neuronal damage. All drug treatments were equally effective in decreasing the number and severity of seizures during electrical stimulation. In the vigabatrin group, the damage to the hilar somatostatin-immunoreactive (SOM-ir) neurons and hippocampal CA3c pyramidal cells was less severe than in the vehicle (SOM-ir, P < 0.01; CA3c, P < 0.05) and carbamazepine (SOM-ir, P < 0.01; CA3c, P < 0.05) groups. In the carbamazepine and combination groups, the severity of neuronal damage in the hippocampus did not differ from that in vehicle-treated animals. The amygdaloid neurons were not protected by any of the treatments. Our results show that even though vigabatrin and carbamazepine treatments had similar anticonvulsant efficacy during the perforant pathway stimulation, only vigabatrin but not carbamazepine decreased seizure-induced neuronal damage. Vigabatrin decreased neuronal damage in the hippocampus but not in the amygdala. These results demonstrate that different brain regions and neuronal networks may be protected unequally by different anticonvulsants.

Amygdala↗