SEARCH · PubMed Health

Results for “selective vulnerability”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed2001

Methylmercury has a selective effect on mitochondria in cultured astrocytes in the presence of [U-(13)C]glutamate.

The effect of methylmercury on glutamate metabolism was studied by (13)C magnetic resonance spectroscopy. Cerebral cortical astrocytes were pretreated with methylmercury, either 1 microM for 24 h, or 10 microM for 30 min, and subsequently with 0.5 mM [U-(13)C]glutamate for 2 h. Labeled glutamate, glutamine, aspartate and glutathione were present in cell extracts, and glutamine, aspartate and lactate in the medium of all groups. HPLC analysis of these amino acids showed no changes in concentrations between groups. Surprisingly, the amounts of [U-(13)C]glutamate and unlabeled glucose taken up by the astrocytes were unchanged. Furthermore, the amounts of most metabolites synthesized from [U-(13)C]glutamate were also unchanged in all groups. However, formation of [U-(13)C]lactate was decreased in the 10 microM methylmercury group. This was not observed for labeled aspartate. It is noteworthy that both [U-(13)C]lactate and [U-(13)C]aspartate can only be derived from [U-(13)C]glutamate via mitochondrial metabolism. [U-(13)C]glutamate enters the tricarboxylic acid cycle (located in mitochondria) after conversion to 2-[U-13C]oxoglutarate and [U-(13)C]aspartate is formed from [U-(13)C]oxaloacetate, as is [U-(13)C]lactate. [U-(13)C]lactate can also be formed from [U-(13)C]malate. This differential effect on labeled aspartate and lactate indicates cellular compartmentation and thus selective vulnerability of mitochondria within the astrocytes to the effects of methylmercury. The decreased lactate production from glutamate might be detrimental to surrounding cells since lactate has been shown to be an important substrate for neurons.

Animals↗

PubMed2001

Increased cAMP immunostaining in cerebral vessels in Alzheimer's disease.

Increasing evidence suggests that up-regulation of the cAMP-second messenger system is implicated in Alzheimer's disease neurodegeneration. Since previous studies reported an increased level of cAMP in microvessels of Alzheimer's patients compared with those from non-demented elderly controls, we have carried out an immunohistochemical study to compare cAMP immunostaining in brain vessels from patients with dementia and neuropathological criteria of Alzheimer's disease (n=5) with those of age-matched patients (n=10). We have also included a control group of adult patients (n=5) to evaluate the role of aging separate from the effects of dementia. Our results demonstrated an increased cAMP immunostaining in cerebral cortical and meningeal vessels from Alzheimer's patients compared to nondemented elderly and adult controls. Vascular cAMP immunostaining was mainly observed in frontal and temporal cortex, the hippocampus being the region that showed the more intense and widespread vascular cAMP immunostaining. We also observed a conspicuous vascular beta-amyloid immunostaining specifically in those vessels that showed the highest cAMP immunostaining. We suggest that increased vascular cAMP immunostaining is mainly localised in the selectively vulnerable targets of neurodegeneration that characterise AD. Moreover, the co-immunolocalisation of cAMP and beta-amyloid protein in cerebral vessels of patients with AD suggests a possible role of cAMP up-regulation in the accumulation of those amyloidogenic peptides.

Aged↗

PubMed2003

Prenatal choline deficiency decreases the cross-sectional area of cholinergic neurons in the medial septal nucleus.

Levels of dietary choline in utero influence postnatal cognitive performance. To better understand this phenomenon, forebrain cholinergic neurons were studied in the 8-9 month old offspring of dams fed a control or choline-deficient diet from EDs 11-17. Serial sections were immunostained with antibodies against p75, a cholinergic marker. Neuronal morphology was analyzed in the basal forebrain, a heterogeneous area composed of several structures including the medial septal nucleus (MSN), nucleus of the diagonal band (DB), and the nucleus basalis of Meynert (NB). Neuronal cross-sectional areas were selectively reduced in the MSN of choline-deficient animals, compared to controls, but cell counts were not altered. Our findings suggest that cholinergic medial septal neurons may be selectively vulnerable to in utero choline deficiency.

Anatomy, Cross-Sectional↗

PubMed2003

3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson's disease pathogenesis.

In Parkinson's disease (PD), there is a highly selective loss of dopamine (DA) neurons in the substantia nigra (SN) greater than in the ventral tegmental area (VTA). The simplest explanation for selective DA neuron loss in PD is that DA is toxic and, because only DA neurons contain significant amounts of DA, this highly localized synthesis of DOPAL accounts for selective vulnerability of DA neurons. However, the large concentrations of DA required to produce in vivo toxicity cast doubt on its role in PD pathogenesis. Alpha-synuclein (alpha-syn) is the major component of the Lewy body, the pathological marker of PD, and is genetically linked to the disease. Recent studies indicate that alpha-syn neurotoxicity is mediated by a free radical generating metabolite of DA. Here we test the hypothesis that 3,4-dihydroxyphenylacetaldehyde (DOPAL), the monamine oxidase metabolite of DA, mediates DA toxicity in vivo. We injected DOPAL, DA and its oxidative, reduced and methylated metabolites into rat SN and VTA. Five days post-surgery, the injection sites were evaluated in Nissl preparations and with tyrosine hydroxylase (for DA neurons), neuronal nuclear antigen (for neurons) and glial fibrillary acidic protein (for astrocytes) immunoreactivities. Lesion size in SN vs. VTA was compared using morphometry. DOPAL at concentrations as low as 100 ng was toxic to DA SN neurons>DA VTA neurons>glia. Neither DA nor its other metabolites showed evidence of neurotoxicity at fivefold higher doses. However, 20 microg of DA produced lesions in the SN and VTA. We conclude that DOPAL is the toxic DA metabolite in vivo. Implications for a unified hypothesis for PD pathogenesis are discussed.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1997

Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra.

Complex I dysfunction has been implicated in the pathogenesis of Parkinson's disease and in the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a Parkinsonian syndrome in experimental animals and humans. Rotenone is an insecticide which is a specific inhibitor of complex I. We examined the pattern of central nervous system damage produced by i.v. systemic administration of rotenone in rats. Rotenone produced selective damage in the striatum and the globus pallidus, but the substantia nigra was spared. These results are consistent with prior reports suggesting that the selective vulnerability of the substantia nigra to MPTP involves both uptake by the dopamine transporter as well as complex I inhibition, and they show that rotenone produces a unique pattern of central nervous system damage.

Animals↗

PubMed1997

Postischemic, systemic administration of polyamine-modified superoxide dismutase reduces hippocampal CA1 neurodegeneration in rat global cerebral ischemia.

Antioxidant enzymes such as superoxide dismutase (SOD) have shown neuroprotective effects in animal models of cerebral ischemia, but only at very high doses. Modifications to increase the plasma half-life or blood-brain barrier (BBB) permeability of SOD have resulted in limited neuroprotective effects. No one has demonstrated neuroprotection with postischemic administration. The specific aim of the present study was to administer systemically a polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, following global cerebral ischemia in rats and analyze the effects on the selective vulnerability of CA1 hippocampal neurons. Following 12 min of four-vessel occlusion, global cerebral ischemia, male Wistar rats were dosed (i.v.) with either saline, native SOD (5000 U/kg), polyamine-modified SOD (5000 U/kg), or enzymatically inactive, polyamine-modified SOD (2.1 mg/kg) twice daily for 3 days. Neuroprotective effects on hippocampal CA1 neurons were assessed using standard histological methods. Saline-treated animals had very few remaining CA1 neurons (1.44 +/- 0.60 neurons/reticle; x +/- S.E.M.) compared to sham rats (58.57 +/- 0.69). Native (10.38 +/- 2.96) or inactive, polyamine-modified SOD (7.32 +/- 2.68) did not show significant neuroprotective effects. Polyamine-modified SOD, however, resulted in the survival of significantly more CA1 neurons (24.61 +/- 5.90; P < 0.01). Postischemic, systemic administration of polyamine-modified SOD, having increased BBB permeability and preserved enzymatic activity, significantly reduced hippocampal CA1 neuron loss following global cerebral ischemia. Similar modification of other antioxidant enzymes and neurotrophic factors with polyamines may provide a useful technique for the systemic delivery of therapeutic proteins across the BBB for the treatment of stroke and other neurodegenerative disorders.

Animals↗

PubMed1998

The development of a new mouse model of global ischemia: focus on the relationships between ischemia duration, anesthesia, cerebral vasculature, and neuronal injury following global ischemia in mice.

A new model for mouse global ischemia is presented, and the relationship of ischemia duration, cerebral vasculature, and ischemic neuronal injury has been determined. CD-1 mice anesthetized by chloral hydrate were subjected to global ischemia by bilateral common carotid artery occlusion under controlled ventilation for 3, 5, and 10 min. After evaluating the patency of the posterior communicating artery (PcomA) as hypoplastic or normoplastic, neuronal injury was independently determined in the striatum, cortex, and hippocampus in each hemisphere. Ischemic injury was strongly correlated with not only ischemia duration, but also with the patency of the PcomAs. Furthermore, neuronal injury developed in a delayed fashion after 3-min ischemia, while it was maximized at 24 h after 10-min ischemia. Physiological studies showed the induction of slight hypotension as compared with inhalation anesthesia, and improvement of blood gas data relative to spontaneous respiration. These data demonstrate the usefulness of this method to induce selective vulnerability and delayed neuronal cell death in mice, and to provide a useful model to study the detailed mechanism of global ischemia using transgenic or knockout mutant mice.

Anesthesia↗

PubMed1998

Temporal ordering of pathogenic events following transient global ischemia.

Rats were subjected to transient global ischemia (four vessel occlusion) and time-related changes in the selectively vulnerable hippocampal field CA1 were characterized. The assessment included ex vivo field responses to afferent stimulation, silver staining, calpain-induced spectrin breakdown, chromatolysis, and cell death, beginning at 6 h post-ischemia and continuing until total disintegration of the pyramidal cells occurred several days later. The earliest change observed was a modest increase in the slope and amplitude of field CA1 potentials (at 6 h). The hyperresponsiveness was most apparent at higher stimulation currents and persisted unchanged at 16 h post-ischemia. Three effects became detectable within 24 h, post-ischemia: (a) an increase in concentrations of calpain-mediated, spectrin breakdown products; (b) enhanced silver staining in the deep pyramidal neurons of the field CA1 with lesser, though still apparent, staining of stratum radiatum, and (c) a decrease in amplitude and slope of field CA1 responses to afferent stimulation. Both the concentration of spectrin breakdown products and the intensity of silver staining progressively increased to a maximum at four days post ischemia, while the amplitude and slope of the field responses dropped to a very low level between 24 and 48 h. Disturbances of Nissl staining were finally evident at 48 h, with nearly complete disappearance of staining at five days post-ischemia. This study provides the first demonstration of a close and early temporal relationship between calpain proteolysis, subcellular damage to the pyramidal cells and their loss of function following global ischemia, prior to their eventual death.

Animals↗

PubMed1998

2'-Deoxyadenosine selectively kills nonneuronal cells without affecting survival and growth of chick dorsal root ganglion neurons.

Recently, we have demonstrated that adenosine and 2'-deoxyadenosine are toxic to embryonic sympathetic neurons and proposed that purine and pyrimidine metabolism may play a critical role in the growth and development of sympathetic neurons. To extend this hypothesis further, we examined the effects of these nucleosides on two other neuronal populations in the chick embryo, sensory dorsal root ganglion neurons and parasympathetic ciliary ganglion neurons. Now, we show that 2'-deoxyadenosine and adenosine have no visible adverse effect on the viability of either sensory or parasympathetic neurons. Instead, 2'-deoxyadenosine proved to be highly toxic to the nonneuronal cells. The toxic effects of 2'-deoxyadenosine were markedly enhanced by inhibition of adenosine deaminase. In contrast, adenosine was much less toxic to nonneuronal cells than 2'-deoxyadenosine and its effect was not potentiated by inhibition of adenosine deaminase. Priming of pyrimidine pools by exogenous uridine and the specific inhibitor of the nucleoside transporter, nitrobenzylthioinosine, did not protect nonneuronal cells from 2'-deoxyadenosine toxicity. Since phosphorylation of internalized nucleosides was a key step in the initiation of toxicity in sympathetic neurons, adenosine kinase activity was compared in sensory and sympathetic neuronal cultures. The adenosine kinase activity in dorsal root ganglion cultures was only 20% of that in sympathetic ganglion cultures. Furthermore, inhibition of phosphorylation by blocking 2'-deoxyadenosine kinase with iodotubercidin and 5'-amino-5'-deoxyadenosine had no protective effect against 2'-deoxyadenosine toxicity. [3H]-thymidine incorporation was inhibited over 90% by 2'-deoxyadenosine as early as 6 h following its addition and for up to 4 days, suggesting inhibition of proliferation of nonneuronal cells by 2'-deoxyadenosine. The nucleoside was also able to wipe out already well established nonneuronal cells, leaving behind an enriched population of sensory neurons. The selective vulnerability of nonneuronal cells to 2'-deoxyadenosine offers a convenient and effective tool for removing nonneuronal cells from neuronal cultures as well as providing a new model for studying the mechanisms of nucleoside toxicity.

Adenosine↗

PubMed1998

A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain.

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.

Animals↗

PubMed1999

Delayed induction of JunB precedes CA1 neuronal death after global ischemia in the gerbil.

The immediate early genes (IEGs), c-jun, junB and c-fos are expressed after global ischemia in the gerbil. The role of these genes remains unclear. Whilst moderate ischemia (7 min) causes delayed CA1 neuronal death, pre-conditioning with mild ischemia (2 min) neuroprotects the CA1 subfield. This differential response allows the specific expression patterns of IEGs to be associated with either delayed neuronal death, or cell survival, depending upon the insult severity. Using a graded insult strategy we have shown that (1) early IEG expression is prominent in the neuronal layers of the CA3, hilar and dentate regions, and (2) a delayed, secondary wave of JunB expression is localized to the selectively vulnerable CA1 neuronal layer after moderate ischemia. This expression precedes the histological and histochemical features of neuronal death. Delayed JunB expression was not observed in animals subject to 2 min ischemia. The glial fibrillary acidic protein (GFAP) promotor possesses an AP-1 binding site, the target for IEG dimers. To examine the possible link between IEG expression and astrocyte activation the transcriptional activation of GFAP was assessed. GFAP mRNA was evident within 8 h of ischemia after both insults. The extent of the astrocytic reaction was dependent upon the severity of the ischemia. The temporospatial distribution of IEG and GFAP expression differed, indicating that glial activation is unlikely to be regulated by the hippocampal expression of IEGs. We conclude that early IEG expression is involved in signalling mechanisms that invoke neuroprotective effects in the dentate and CA3 regions, and that delayed JunB expression in the CA1 subfield is associated with neuronal death, and may be involved in the commitment or execution phases of cell death. Early astrocytic responses may play a role in the mechanism of ischaemic tolerance.

Animals↗

PubMed1999

Differential synaptic distribution of the AMPA-GluR2 subunit on GABAergic and non-GABAergic neurons in the basolateral amygdala.

The cellular and ultrastructural distribution patterns of the AMPA glutamate receptor subunit, GluR2, were determined in the rat basolateral amygdala. GluR2 immunoreactivity was widely and uniformly distributed in the basolateral nucleus, with both pyramidal and non-pyramidal neurons labelled. In fact, double label immunohistochemical analyses demonstrated that over 90% of the GABAergic interneurons were labelled for GluR2. Electron microscopic analyses further confirmed the presence of GluR2 in the soma and dendrites of GABAergic interneurons as well as in the soma, spines and dendritic shafts of pyramidal cells. As in our parallel study in the rat hippocampus, immunogold analyses revealed that GluR2 immunoreactivity was frequently preferentially located at asymmetric synapses on both pyramidal cell spines and shafts, as well as the dendritic processes and soma of GABAergic interneurons. However, the number of immunogold particles per labelled synapse on GABAergic neurons was significantly lower than at similar labelled asymmetric synapses on spines of presumed pyramidal cells. Given that the presence of GluR2 within the AMPA receptor complex decreases calcium flux, these data indicate that GABAergic local circuit neurons might possess AMPA receptors with higher calcium permeability on average than pyramidal cells, as has been suggested for hippocampus. Such cell class-specific differences in the subunit representation and resultant channel properties of AMPA receptors have implications for response properties as well as selective vulnerability of neurons within the basolateral nucleus of the amygdala.

Amygdala↗

PubMed1999

Regional patterns of neuronal death after deep hypothermic circulatory arrest in newborn pigs.

OBJECTIVES: Deep hypothermic circulatory arrest (DHCA) widely used during neonatal heart surgery, carries a risk of brain damage. In adult normothermic ischemia, brain cells in certain regions die, some by necrosis and others by apoptosis (programmed cell death). This study characterized regional brain cell death after DHCA in newborn pigs. METHODS: Eighteen piglets underwent 90 minutes of DHCA and survived 6 hours, 2 days, or 1 week. Six piglets underwent surgery alone or deep hypothermic cardiopulmonary bypass and survived 2 days. Three piglets received no intervention (control). Brain injury was assessed by neurologic and histologic examination and correlated with perioperative factors. Apoptosis and necrosis were identified by light microscopic analysis of cell structure and in situ DNA fragmentation (TUNEL). RESULTS: All groups subjected to DHCA had brain injury by neurologic and histologic examination, whereas the other groups did not. DHCA damaged neurons in the neocortex and hippocampus and occasionally in the striatum and cerebellum. Damaged neurons in the neocortex were mainly apoptotic and in the hippocampus, a mixture of necrotic and apoptotic neurons. Apoptosis and necrosis were apparent in all DHCA groups even though neurologic deficits improved over the week's survival. Neocortical and hippocampal damage correlated with blood glucose, hematocrit, and arterial PO(2) during and after cardiopulmonary bypass. CONCLUSIONS: In neonates, neocortical and hippocampal neurons are selectively vulnerable to death after DHCA. Both apoptosis and necrosis contribute to neuronal death, beginning early in reperfusion and continuing for days. These data suggest the need for several neuroprotective strategies tailored to the region and death process, initiated during the operation and continued after the operation.

Analysis of Variance↗

PubMed1996

Inhibition of GABA-gated chloride channels in brain by the arachidonic acid metabolite, thromboxane A2.

Previously, we showed that arachidonic acid and prostaglandin metabolites inhibited GABAA responses in rat cerebral cortex. Thromboxane A2 (TXA2), a metabolite of arachidonic acid, has potent actions on blood vessels and platelets, but its actions on neurons are not known. Here, we examined the effects of several TXA2 analogs on the functional and binding characteristics of GABAA receptors in rat brain. The stable analogs of TXA2, pinane and carbocyclic TXA2, and the TXA2 agonist, U-46619, inhibited muscimol-induced 36Cl- uptake in cerebral cortical synaptoneurosomes. Carbocyclic TXA2 decreased the maximal response to muscimol, consistent with a non-competitive interaction. The TXA2 antagonist, SQ 25,548, did not block the effects of either arachidonic acid or carbocyclic TXA2. Neither the biologically inactive metabolite of TXA2, TXB2, nor carbacyclin, a stable analog of prostacyclin (prostaglandin I2) had an effect on GABAA responses. Thus the pharmacology differs from that in vascular smooth muscle and platelets. To determine if GABAA receptors were sensitive to the thromboxanes, the effect of pinane TXA2 on the binding of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) to GABA-gated Cl- channels was measured using receptor autoradiography. Pinane TXA2 inhibited [35S]TBPS binding in a regionally selective and non-competitive manner; the greatest inhibition was in the cerebral cortex, hippocampus and striatum, areas which are selectively vulnerable to cerebral ischemia. We conclude that TXA2 can interact with neuronal membranes to inhibit GABA receptor function, independent of its actions on the cerebrovasculature and on glial cells. This may be important during pathologic states such as ischemia, when TXA2 accumulates in extracellular spaces.

Animals↗

PubMed1989

Controversies concerning neonatal seizures.

Five issues are discussed with respect to the diagnosis, etiology, treatment, prognosis, and pathogenesis of neonatal seizures. The presentation of a newborn with seizures represents a true emergency and frequently indicates significant neurologic dysfunction or damage to the immature nervous system. Despite the urgency to establish a diagnosis, several unique aspects of neonatal seizures impede prompt recognition. In addition, several etiologic possibilities may be associated with seizures. The efficacy of antiepileptic drugs and the prediction of outcome of patients with neonatal seizures are controversial. Experimental research in developing animals suggests both a selective vulnerability and resistance of the brains of immature animals subjected to neonatal seizures.

Asphyxia Neonatorum↗

PubMed2006

[Acute bilateral deafness and facial diplegia as a presentation of occlusion of the basilar artery].

INTRODUCTION: Sudden bilateral deafness and facial weakness are unusual presentations of brain stem stroke. OBSERVATION: We report the case of a patient who presented successively sudden bilateral deafness and facial diplegia in correlation with a brain stem stroke but without any ischemic pontine lesion. DISCUSSION: Unlike our case, all of the earlier publications, have reported the presence of ischemic pontine lesions in patients with bilateral deafness and facial diplegia. Selective vulnerability of inner ear to ischemia has been hypothesized but cannot explain the facial diplegia. CONCLUSION: Our case would suggest extra-neuraxis failure by ischemia of the acoustico-facial nerve.

Acute Disease↗

PubMed2002

Concept of activity-induced cell death in epilepsy: historical and contemporary perspectives.

Selective neuronal loss following status epilepticus was first described just under 100 years ago. The acute pathology following status epilepticus was shown to be 'ischemic cell change' and was assumed to arise through hypoxia/ischemia. Less than 30 years ago it was proposed, from experiments in primates, that the selective neuronal loss in hippocampus and cortex resulted from the abnormal electrical discharges. Selectively vulnerable neurons show swollen, calcium-loaded mitochondria in the soma and focally in dendrites. Burst firing with a massive Ca2+ entry needs to be sustained for 30-120 min to produce necrotic cell death. Lesser stress may produce apoptosis or immediate early gene expression with enhanced expression of many enzymes and receptor subunits. Changes in enzyme, transporter, ion-channel or receptor function or in network properties may lead to altered vulnerability to the effects of seizures. This type of modification and the cumulative effect of oxidative damage to proteins and lipids may explain the long-term consequences of repetitive brief seizures.

Animals↗

PubMedDate not supplied

Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats.

Changes of emotional behavior and neuronal cell loss in the hippocampus were investigated after pentylenetetrazol (PTZ) induced kindling in rats. Behavioral and morphological changes were studied in partially and fully kindled rats and after different postkindling periods comparing to the controls. The resident-intruder test indicated a diminished offensive behavior in partially and fully kindled animals. The open-field and the cat-odor exposition tests reveal changes in defensive behavioral pattern only in fully kindled rats. A decrease of exploratory locomotion and an increase in freezing were assessed in the open-field and the cat-odor exposition test, respectively, up to 10 weeks after the end of kindling. The first damaged neurons (CA4 region) were observed in the partially kindled group (PK), correlating with an increase in the glial fibrillary acidic protein (GFAP)-immunoreactivity (GFAP-IR) and hypertrophy of astrocytes. The most significant increase in the number of damaged neurons was detected 24 h after completion of kindling (selective vulnerability: CA4/CA1>DG>CA2+CA3). The neuronal loss went on for 10 weeks postkindling. A low correlation between the number of Stage 4 kindling seizures and the number of damaged hippocampal neurons was found 24 h after the end of kindling in individual rats. The present results demonstrate that PTZ kindling goes along with long-lasting changes in emotional behavior. The alterations of the defensive behavior after the termination of kindling can be interpreted as depression-like and are obviously associated with a characteristic pattern of neuronal loss in various hippocampal regions.

Animals↗