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PubMed2002

Functional heterogeneity in human olfactory cortex: an event-related functional magnetic resonance imaging study.

Studies of patients with focal brain injury indicate that smell perception involves caudal orbitofrontal and medial temporal cortices, but a more precise functional organization has not been characterized. In addition, although it is believed that odors are potent triggers of emotion, support for an anatomical association is scant. We sought to define the neural substrates of human olfactory information processing and determine how these are modulated by affective properties of odors. We used event-related functional magnetic resonance imaging (fMRI) in an olfactory version of a classical conditioning paradigm, whereby neutral faces were paired with pleasant, neutral, or unpleasant odors, under 50% reinforcement. By comparing paired (odor/face) and unpaired (face only) conditions, odor-evoked neural activations could be isolated specifically. In primary olfactory (piriform) cortex, spatially and temporally dissociable responses were identified along a rostrocaudal axis. A nonhabituating response in posterior piriform cortex was tuned to all odors, whereas activity in anterior piriform cortex reflected sensitivity to odor affect. Bilateral amygdala activation was elicited by all odors, regardless of valence. In posterior orbitofrontal cortex, neural responses evoked by pleasant and unpleasant odors were segregated within medial and lateral segments, respectively. The results indicate functional heterogeneity in areas critical to human olfaction. They also show that brain regions mediating emotional processing are differentially activated by odor valence, providing evidence for a close anatomical coupling between olfactory and emotional processes.

Adolescent↗
PubMedDate not supplied

Rapid alterations in diffusion-weighted images with anatomic correlates in a rodent model of status epilepticus.

BACKGROUND AND PURPOSE: Diffusion-weighted MR imaging has emerged as a noninvasive tool for the detection of regional neuronal damage. We hypothesize that changes in diffusion-weighted images will correlate with pathophysiologic alterations caused by pilocarpine-induced status epilepticus. METHODS: MR images of brain tissues were examined in vivo by use of T2- and diffusion-weighted imaging at 3, 6, 12, and 24 hours after pilocarpine-induced seizures. Histologic verification of neuronal damage was also performed after imaging to assess the extent and the time course of neuronal cell death. RESULTS: The piriform cortex, amygdala, and retrosplenial (and somatosensory) cortex displayed significant apparent diffusion coefficient (ADC) decreases 12 hours after seizure initiation. In contrast, an ADC rise of 19% was observed in the hippocampus 24 hours after seizure induction. Histologic data from the piriform cortex and amygdala confirmed severe neuronal loss, whereas hippocampal damage was much less pronounced at 12 hours. Interestingly, very little histologic damage was seen in the retrosplenial cortex. CONCLUSION: This study capitalized on diffusion-weighted imaging as a sensitive technique for the early identification of seizure-induced neuronal damage and differentiation of regional severity of these alterations. Hippocampal neuropathology is slower and longer in duration (approximately 7 days), while the piriform cortex and amygdala exhibit very rapid neurodegenerative alterations (approximately 24 hours) after pilocarpine-induced status epilepticus. These histologic changes are reflected in opposing ADC values within these regions.

Analysis of Variance↗
PubMed1992

Seizure activity-induced changes in polyamine metabolism and neuronal pathology during the postnatal period in rat brain.

Systemic injection of kainic acid (KA) does not cause neuronal pathology in limbic structures in rat brain prior to postnatal day (PND) 21. The present study tested if the development of the pathogenic response is associated with the maturation of a link between seizure activity and polyamine metabolism. Pathology was assessed with histological techniques and with the binding of [3H]Ro5-4864, a ligand for the peripheral type benzodiazepine binding sites (PTBBS), a marker of glial cell proliferation. In agreement with previous results, peripherally administered kainate at doses sufficient to induce intense behavioral seizures produced a loss of Nissl staining in hippocampus after PND 21 but not at earlier ages. The pattern of neuronal damage observed after PND 21 resembled that found in adult animals: extensive losses of Nissl staining in area CA3 of hippocampus and in piriform cortex, more modest effects in CA1 and sparing of the granule cells of the dentate gyrus. Similarly, no increase in [3H]Ro5-4864 binding as a result of KA administration was observed in hippocampus and piriform cortex until PND 21. Ornithine decarboxylase (ODC) activity and putrescine levels were high in the neonatal brain and decreased to reach adult values by PND 21. KA-induced seizure activity did not significantly alter both variables until PND 21. After PND 21, ODC activity and putrescine levels markedly increased 16 h after KA-induced seizure activity in hippocampus and piriform cortex. The magnitude of the effects increased between PND 21 and PND 30, at which point the changes in both parameters were comparable to those found in adults. Polyamines stimulate the activity of the calcium-dependent proteases calpain in brain fractions and may increase calpain-mediated proteolysis in situ. In accord with this, kainate-induced breakdown of spectrin, a preferred substrate of calpain, measured 16 h after KA injection followed a developmental curve parallel to that for kainate-induced increases in putrescine levels. These results indicate that the onset of vulnerability to seizure activity triggered by kainic acid is correlated with the development of an ODC/polyamine response to the seizures and further support a critical role for the ODC/polyamine pathway in neuronal pathology following a variety of insults.

Animals↗
PubMed1996

Change in neurotrophins and their receptor mRNAs in the rat forebrain after status epilepticus induced by pilocarpine.

We studied the effects of status epilepticus (SE) induced by lithium chloride/pilocarpine treatment on gene expression of neurotrophins of the nerve growth factor (NGF) family and of their high-affinity receptors of the tyrosine protein kinase (trk) family in the forebrain. Using in situ hybridization (ISH), we demonstrated an early (3 h after treatment) increase in brain-derived neurotrophic factor (BDNF) and trkB mRNA expression in the dentate gyrus, amygdala, and piriform cortex, as well as widespread increases in the cerebral cortex. NGF mRNA, but not the mRNA of its receptor trkA, was increased in the dentate gyrus. In contrast, 12 h after treatment, neurotrophin-3 (NT-3) decreased, and its receptor trkC mRNA increased. There was no change in NT-4 mRNA levels. All changes were blocked by pretreatment with scopolamine, a muscarinic antagonist. The noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine blocked NGF, BDNF, and trkB mRNA increases in the hippocampus and cerebral cortex, but not in the amygdala and piriform cortex. In contrast, ketamine did not affect NT-3 and trkC changes. These results provide a complete description of changes in mRNA levels of neurotrophins and their receptors in the forebrain after SE and supply additional data supporting the view that neurotrophin gene expression is related to abnormal neuronal activity.

Animals↗
PubMed1994

Hippocampal kindling protects several structures from the neuronal damage resulting from kainic acid-induced status epilepticus.

In an attempt to study the effects of piriform cortex damage on kindled seizure propagation, we administered kainic acid (12 mg/kg; i.p.) to rats previously kindled from the dorsal hippocampus. Unexpectedly, the ensuing status epilepticus (SE) in the kindled rats did not result in the piriform cortex damage normally observed in naive rats. As a result of this surprising finding, a more comprehensive investigation was undertaken to compare dorsal hippocampal kindled and control rats on their electrographic and behavioral SE development and subsequent brain damage. The SE induction profile and the pattern of brain damage observed in our control rats was similar to previous reports [Neuroscience, 14 (1985) 375-403; Brain Res., 218 (1981) 299-318]. By contrast, although fewer kindled rats than controls responded to the initial dose of kainic acid with electrographic and behavioral seizures, those many kindled rats that did respond, showed a pattern of SE induction that was different from controls. Kindled rats manifested fewer 'wet dog shakes', more generalized convulsions and a faster development of severe limbic status (SLS) than controls. In addition, without pharmacological intervention, the SLS continued longer in kindled rats than in controls. Histological examination revealed brain damage in kindled rats that was markedly different from controls. Unlike controls, kindled rats had no damage in the piriform cortex or substantia nigra reticulata and minimal hippocampal damage, yet showed midline thalamic and anterior olfactory nuclei damage similar to controls. These differences were observed from 1 to 28 days after kindling. Although the mechanism(s) of this kindling-based neuroprotection is not known, its discovery should add importantly to our understanding of epilepsy-induced alterations of subsequent neuronal function.

Animals↗
PubMed2003

Alterations in brain glutathione homeostasis induced by the nerve gas soman.

Public awareness of the dangers of chemical and biological warfare has been heightened in recent times. In particular, chemical nerve agents such as soman and its analogs have been developed and used in war as well as recent incidents, such as in Iraq and Japan. Soman, a rapid acting acetylcholinesterase inhibitor, produces a status epilepticus that leads to extensive neuropathology in vulnerable brain regions (eg, piriform cortex and hippocampus). This study was undertaken to determine whether oxidative mechanisms are involved in brain pathology during soman toxicity. Intracellular thiols such as glutathione (GSH) and protein sulfhydryls (PrSH) are among the most critical antioxidants used to combat oxidative stress. Here we report that during the seizure phase (1 h post soman exposure), PrSH levels in piriform cortex and hippocampus were decreased without changes in glutathione (GSH) levels. However, by 24 h post soman exposure (pathology phase), GSH levels were decreased by nearly 50% in the piriform cortex with a corresponding decrease in PrSH groups. The shift to a more oxidized thiol status indicates that oxygen free radicals likely participate in the neuropathology associated with soman-induced seizures.

Animals↗
PubMed1986

Neurogenesis in the rat primary olfactory cortex.

Neurogenesis in the rat primary olfactory cortex was examined with [3H]thymidine autoradiography. The experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on E13-E14, E14-E15....E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24 hr periods were quantified at selected anatomical levels of the anterior and posterior piriform cortex, dorsal lateral peduncular cortex, and posterior two-thirds of the ventral agranular insular cortex. Throughout most of the primary olfactory cortex, deep cells are generated earlier than superficial cells: the 'inside-out' pattern. Neurons in the anterior (prepiriform) cortex are located lateral to the caudal anterior olfactory nucleus and olfactory tubercle, and are generated mainly between E14 and E18 in a caudal (older) to rostral (younger) neurogenetic gradient. Neurons in the posterior (periamygdaloid) cortex are located lateral to the caudal olfactory tubercle and amygdala, and are generated mainly between E14 and E17 simultaneously along the rostrocaudal plane. Superficial cells in the piriform cortex have some additional neurogenetic gradients; ventromedial cells forming transition zones with either the olfactory tubercle or amygdala originate earlier than cells located dorsally and laterally. In the posterior piriform cortex, younger neurons are located at middle dorsoventral levels while older neurons lie above and below. Neurons in the dorsolateral peduncular cortex originate between E14 and E20 in a caudal to rostral gradient of neurogenesis; caudal parts also have a lateral to medial neurogenetic gradient. The most lateral part of the dorsolateral peduncular cortex is unique and does not have the typical 'inside-out' cortical neurogenetic gradient. Neurons in the ventral agranular insular cortex (area 13) originate mainly between E15 and E17 in combined caudal to rostral and ventral to dorsal neurogenetic gradients. The neurogenetic gradients in the primary olfactory cortex, along with patterns of neurogenesis throughout the olfactory projection field are related to the termination patterns of afferents from the main olfactory bulb.

Animals↗
PubMed1991

Systemic kainic acid administration in rats: effects on kynurenic acid production in vitro and in vivo.

The endogenous broad spectrum excitatory amino acid receptor antagonist kynurenic acid (KYNA) has anti-convulsant properties and has been hypothetically linked to the pathogenesis of seizure disorders. Using brain slices and in vivo microdialysis in unanesthetized rats, KYNA synthesis from its bioprecursor kynurenine was therefore examined in the kainate model of temporal lobe epilepsy. Tissue slices obtained during status epilepticus from animals injected with kainate (10 mg/kg, sc) did not show changes in KYNA production. One month after kainate injection, KYNA synthesis was substantially increased in slices of piriform cortex (380% of control) and hippocampus (227% of control) but not in striatal slices. Since KYNA production takes place preferentially in glia, these increases are likely to be due to the selective neuronal loss and reactive astrogliosis known to exist in chronically kainate-lesioned brains. Microdialysis, performed in the piriform cortex only, confirmed the in vitro results. Thus, no change in extracellular KYNA concentration was detected within 4 h after systemic kainate administration but a significant increase was observed 1 month later. Moreover, the veratridine-induced decrease in KYNA production detectable in normal tissue was not observed in the neuron-depleted piriform cortex. The data are discussed with regard to a possible role of glia-derived KYNA in temporal lobe epilepsy.

Animals↗
PubMed2003

Degeneration of the amygdala/piriform cortex and enhanced fear/anxiety behaviors in sodium pump alpha2 subunit (Atp1a2)-deficient mice.

The sodium pump is the enzyme responsible for the maintenance of Na+ and K+ gradients across the cell membrane. Four isoforms of the catalytic alpha subunit have been identified, but their individual roles remain essentially unknown. To investigate the necessary functions of the alpha2 subunit in vivo, we generated and analyzed mice defective in the alpha2 subunit gene. Mice homozygous for the alpha2 mutation died just after birth and displayed selective neuronal apoptosis in the amygdala and piriform cortex. In these regions, high expression of c-Fos before apoptosis indicated neural hyperactivity, and re-uptake of glutamic acid and GABA into P2 fraction containing crude synaptosome was impaired. These results indicate that the alpha2 subunit plays a critical role regulating neural activity in the developing amygdala and piriform cortex. Further supporting a role of the alpha2 subunit in the function of the amygdala, heterozygous adult mice showed augmented fear/anxiety behaviors and enhanced neuronal activity in the amygdala and piriform cortex after conditioned fear stimuli.

Amygdala↗
PubMed2001

Cyclin-dependent kinase 4 and cyclin D1 are required for excitotoxin-induced neuronal cell death in vivo.

Systemic administration of the glutamic acid analog kainic acid (KA) causes neuronal cell death in brain-vulnerable regions, such as the piriform cortex, hippocampus, and amygdala in rats. We investigated the relationship between the KA-induced neuronal apoptosis and expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1, key regulators of cell cycle progression. Expression of CDK4 and cyclin D1 was upregulated in neurons of the rat piriform cortex and amygdala 1-3 d after KA administration in vivo. CDK4 and cyclin D1 proteins were induced in the cytoplasm and nuclei of neurons, with a concomitant increase of CDK4- and cyclin D1-positive microglia in the affected areas. Continuous infusion of 100 microm CDK4 or cyclin D1 antisense oligonucleotides into the lateral ventricle using mini-osmotic pumps suppressed the excitotoxin-induced neuronal cell death in the piriform cortex and basolateral amygdaloid nucleus, whereas sense oligonucleotides exhibited no such effect. Although KA administration causes prolonged c-Fos expression in the vulnerable regions that preceded the induction of neuronal apoptosis, the CDK4 or cyclin D1 antisense oligonucleotides exhibited no suppressive effect on c-Fos levels. Our results suggest that CDK4 and cyclin D1 are essential for KA-induced neuronal apoptosis in vivo.

Amygdala↗
PubMed1991

Olfactory projections to the hypothalamus.

Electrophysiological recording, together with anterograde and retrograde axonal tracers, was used to provide a comprehensive description of the origin and distribution of the olfactory input to the lateral hypothalamus. This input was much more substantial to the caudal part of the hypothalamus than to the rostral part and originates from several different areas of the olfactory cortex. Positive responses to electrical stimulation of the olfactory bulb were found consistently in the postero-lateral hypothalamus, but only occasionally at more rostral levels. In agreement with this, injections of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) in the posterior half of the lateral hypothalamus labeled cells in four cortical areas that receive input from the olfactory bulb: the anterior olfactory nucleus, the piriform cortex (in the deepest layer or ventral endopiriform nucleus), the olfactory tubercle (in the deep polymorphic layer), and the anterior cortical nucleus of the amygdala. Injections of WGA-HRP in the anterolateral hypothalamus labeled cells only in the anterior cortical nucleus of the amygdala. Anterograde axonal tracing confirmed these projections. Injections of 3H-leucine in the anterior olfactory nucleus, the piriform cortex, and the olfactory tubercle produced axonal label that was light and confined to the medial forebrain bundle in the rostral hypothalamus but was more substantial and extended throughout the lateral hypothalamic area caudally. Injections in the anterior cortical amygdaloid nucleus labeled axons in the anterior hypothalamus and in the premammillary nuclei as well as in the posterolateral hypothalamic area. In addition, a projection was demonstrated to the nuclei gemini from the polymorphic zone deep to the olfactory tubercle. Injections of two fluorescent retrograde tracers into the mediodorsal nucleus of the thalamus and the posterolateral hypothalamus showed that cells projecting to both diencephalic sites were intermingled in all of the olfactory cortical areas except the anterior olfactory nucleus, where cells were labeled only from the hypothalamus. In the deep layer of the piriform cortex and in the anterior cortical amygdaloid nucleus cells were also double labeled, indicating that they send collateral axons to both parts of the diencephalon.

Amygdala↗
PubMed1996

Seizure activity results in a rapid induction of nuclear factor-kappa B in adult but not juvenile rat limbic structures.

Previous studies have indicated that increased formation of oxygen free radicals is likely to participate in the cascade of events leading to neuronal damage following kainic acid (KA)-induced seizure activity. As reactive oxygen species are involved in signal transduction pathways leading to nuclear factor-kappaB (NF-kappaB) activation, we examined the effects of KA treatment on the activation of NF-kappaB in adult and juvenile rat brain. For comparison, changes in two other transcription factors, activator protein-1 (AP-1) and Sp1, were also determined. In adult rat piriform cortex and hippocampus, significant induction of NF-kappaB was observed at 4 h after KA injection, and the maximal increase was reached at 8-16 h posttreatment. NF-kappaB binding activities returned to control levels by 5 days after injection. NF-kappaB binding activities were slightly decreased in adult rat cerebellum at 8 and 16 h after KA treatment. In the juvenile rat, no significant changes in NF-kappaB binding activity were observed in piriform cortex, hippocampus, and cerebellum after KA injection. Changes in AP-1 binding activity were qualitatively similar to those observed with NF-kappaB in adult but not juvenile rat brain, as AP-1 was significantly induced in juvenile piriform cortex and hippocampus following KA injection. On the other hand, little or no changes in Sp1 activity were detected in adult and juvenile rat brain. Our results provide further evidence that oxidative stress participates in neuronal damage resulting from KA-induced seizure activity.

Age Factors↗
PubMed1986

Effects of dexamethasone on brain edema induced by kainic acid seizures.

The histopathological alterations developing in the hippocampus, piriform cortex and thalamus of the rat brain, the blood-brain barrier damage, and the effects of dexamethasone pretreatment on the brain edema were investigated 4 h following intraperitoneal kainic acid administration. The most pronounced Evans Blue extravasation accompanied by increases in the water and sodium contents and a decrease in the potassium content, were observed in the thalamus. Dexamethasone, injected in a dose of 5 mg/kg 2 h before kainic acid administration, reduced considerably the vasogenic edema and neuronal damage in the thalamus, but the cytotoxic edema of the hippocampus and piriform cortex remained unaltered. Kainic acid-induced seizures lead to the development of vasogenic brain edema mainly in the thalamus, as well as to cytotoxic edema in the hippocampus and piriform cortex. The vasogenic edema seems to contribute to the cell damage in the thalamus. Dexamethasone reduces the vasogenic edema and cell damage in the thalamus, possibly by inducing the synthesis of certain protein(s) with antiphospholipase A2 activity.

Animals↗
PubMed1990

MK-801, an antagonist of NMDA receptors, inhibits injury-induced c-fos protein accumulation in rat brain.

Unilateral lesions of the rat hippocampus produced by needle insertion lead to ipsilateral accumulation of c-fos protein in dentate granule cells and neurons in the piriform cortex, as well as in glial-like cells in the corpus callosum and in ependymal cells lining the lateral ventricle adjacent to the lesion site. C-fos protein was detected immunocytochemically using two different antibodies in formalin-fixed brain sections. The N-methyl-D-aspartate (NMDA) antagonist MK-801 produced a dose- and time-dependent inhibition of c-fos protein accumulation in dentate granule cells and in neurons in the piriform cortex, but did not affect glial or ependymal c-fos protein accumulation. MK-801 at 4 mg/kg injected two hours before lesion inhibited c-fos accumulation. Thus, c-fos protein accumulation in hippocampal neurons and in neurons in the piriform cortex induced after traumatic brain injury involves activation of NMDA receptors.

Animals↗
PubMed1994

Differential effect of thyroid hormone on NGFI-A gene expression in developing rat brain.

NGFI-A is an immediate early gene that is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. We have previously shown that the expression of NGFI-A in the developing rat brain is under the control of thyroid hormone. Now we report, by means of in situ hybridization histochemistry, the differential effect of thyroid hormone on NGFI-A expression in distinct brain regions depending on the developmental stage. NGFI-A messenger RNA (mRNA) content was analyzed in the piriform cortex, striatum, hippocampus, and cerebral cortex of control, hypothyroid, and T3-injected hypothyroid rats at birth and on postnatal days 5 and 15. In the newborn rats, experimental hypothyroidism is associated with reduced levels of NGFI-A mRNA in most of the brain regions studied. On postnatal day 15, the difference in NGFI-A expression between control and hypothyroid rats is less apparent in the striatum or no longer present in the piriform cortex and the hippocampus. In the cerebral cortex, hypothyroidism is associated with reduced levels of NGFI-A mRNA on postnatal day 15. The dentate gyrus is always insensitive to the thyroidal state. Administration of T3 accelerates the recovery of NGFI-A mRNA in 5- and 15-day-old rats. However, in newborn rats, the effect of the hormone is noticeable only in the piriform cortex. We also show that the reduced level of NGFI-A mRNA in hypothyroidism is accompanied by a reduction in the protein level. Convulsions induced by pentylenetetrazole administration resulted in an increased expression of the NGFI-A gene, which is of similar magnitude in control and hypothyroid rats.

Animals↗
PubMed2001

The selective cyclooxygenase-2 inhibitor rofecoxib reduces kainate-induced cell death in the rat hippocampus.

Treatment of male Sprague-Dawley rats with kainic acid (10 mg/kg, i.p.) triggered limbic seizures in 60% of the animals starting within 30 min and lasting for about 6 h. Cyclooxygenase-2 (COX-2) mRNA was strongly induced in the pyramidal cells of the hippocampus, in the amygdala and the piriform cortex after 8 h, as shown by in situ hybridization, and returned to control levels after 72 h. At this time marked cell loss occurred in the CA1-CA3 areas of the hippocampus. We hypothesize that rofecoxib, a selective COX-2 inhibitor, might abbreviate the late neurotoxicity, possibly associated with COX-2 induction. Animals which developed seizures were treated for 3 days with rofecoxib (10 mg/kg, i.p., n = 12) starting 6 or 8 h after kainic acid injection. Histological staining of viable cells confirmed that rofecoxib treatment selectively diminished cell loss in the hippocampus. The TdT-mediated dUTP nick end labelling (TUNEL) technique was used to estimate delayed cell death. Abundant TUNEL-positive cells were detected in seizure rats 72 h after kainic acid injection in pyramidal cells of the hippocampus (CA1-CA3), in cells of the thalamus, the amygdala and the piriform cortex. Treatment with rofecoxib selectively and significantly (P < 0.05) attenuated the number of TUNEL-positive cells in the hippocampus, whereas the cells of the thalamus, amygdala and piriform cortex were not protected. Therefore we conclude that COX-2 might contribute to cell death of pyramidal cells of the hippocampus as a consequence of limbic seizures.

Animals↗
PubMed1999

Dissociation of mossy fiber sprouting and electrically-induced seizure sensitivity: rapid kindling versus adaptation.

It has been shown that massed stimulation (MS) of the amygdala or hippocampus does not result in seizure progression but in the 'phenomenon of adaptation', whereas alternate day rapid kindling (ADRK) produces reliable kindling (Lothman, E.W., Williamson, J.M., 1994. Brain Res. 649, 71-84). The goal of the present experiment was to determine if the two different effects are due to differences in mossy fiber sprouting and/or different seizure and postictal spike propagation patterns. Nine rats underwent MS (66-70 stimulations separated by 5-min interstimulus interval), six were exposed to ADRK (12 stimulations/day, every 30 min, with 4 stimulus days, each separated by 1 stimulus-free day), five rats served as control. All rats had electrodes implanted bilaterally in dorsal and ventral hippocampi (VH) and 14 of them had additional electrodes in the piriform cortex. Animals were stimulated in the left VH at afterdischarge threshold. There was no potentiation in seizure response 4-7 weeks after MS. In contrast, ADRK produced not only kindling but also ongoing epileptogenesis resulting 4-7 weeks later in spontaneous seizures and development of a prolonged convulsive state in response to the initially subconvulsive stimulus. Epileptiform activity during MS was mostly restricted to VH, whereas during ADRK it spread widely among studied structures including piriform cortex. Afterdischarges during MS were elicited frequently but seizures did not progress beyond stage 2-3. During ADRK, afterdischarges were evoked less frequently but seizures reached stage 4-7 by the end of the 3rd and 4th stimulus days. The fully kindled state was not reached at this time, but epileptogenic changes continued to progress. Seven weeks after the initial stimulation, both groups demonstrated mossy fiber sprouting of similar intensity in VH. We suggest, (1) frequent but predominantly local hippocampal afterdischarges induce mossy fiber sprouting, but this is not sufficient to produce significant enhancement in seizure susceptibility, and (2) the involvement of extra-hippocampal structures, possibly piriform cortex, and formation of an aberrant hippocampal-para-hippocampal circuit is required to result in a condition of progressive epileptogenesis.

Adaptation, Physiological↗
PubMed1989

Topographical assessment of accumulated radioactivity from [14C]2-deoxyglucose and [6(-14C)]glucose in rat forebrain at different survival periods.

The uptake and retention of radioactivity was measured in discrete areas of rat brain at different times after i.v. injection of [14C]2-deoxyglucose or [6(-14)C]glucose, in unrestrained rats. In most brain regions, the accumulation of radioactivity from the two compounds was similar when a 30-min survival period for [6(-14)C]glucose was compared to a 45-min survival period for [14C]2-deoxyglucose. However, at those times, autoradiographic images of the hippocampus and piriform cortex appeared distinctly different for [14C]2-deoxyglucose and [6(-14)C]glucose. Relatively more radioactivity accumulated from [14C]2-deoxyglucose, compared to [14C]glucose, in the stratum lacunosum-moleculare of the hippocampus and in layer 4 of the isocortex. In contrast, relatively more radioactivity accumulated from [6(-14)C]glucose, compared to [14C]2-deoxyglucose, in the molecular and granule cell layers of the dentate gyrus, the CA1 pyramidal cell layer of the hippocampus, and in layer 2 of the piriform cortex. When rats were killed 5 min after injection of [6(-14)C]glucose, the relative neuroanatomical distribution of radioactivity was similar to the 30-min survival period, except in layer 4 of the isocortex, where relatively more radioactivity was present at the early time. When rats were killed 5 min after injection of [14C]2-deoxyglucose, in 20 of 24 brain regions examined, the absolute and relative amounts of accumulated radioactivity were similar when compared to that of the 45-min survival period. In contrast, the absolute and relative amounts of radioactivity were significantly greater for the 5-min compared to the 45-min survival period, in the CA1 pyramidal cell field, dentate gyrus, and layer 2 of the piriform cortex. For those regions, the appearance of autoradiograms prepared from rats killed 5 min after administration of [14C]2-deoxyglucose is remarkably similar to the appearance of autoradiograms prepared from rats killed 5 or 30 min after injection of [6(-14)C]glucose. Possible mechanisms are discussed to explain the observed differences in the accumulation of radioactivity in discrete brain regions after injection of [6(-14)C]glucose and [14C]2-deoxyglucose at the different survival times examined.

Animals↗