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A Obenaus

Publications and source records attributed to A Obenaus.

15 recordsLinked to original sources
PubMed2001

Cortical devascularization: quantitative diffusion weighted magnetic resonance imaging and histological findings.

This study investigates the development of a small focal cortical lesion produced in a model of brain injury. Two approaches were chosen: diffusion weighted magnetic resonance imaging (DWI) and histology. DW images were collected before devascularization and at 0.5, 1, 2, 3, 5, 7 and 14 days after treatment. Apparent diffusion coefficient (ADC) maps were calculated from the DW images to quantify lesion development. As a second measure of injury, tissue morphology was analyzed using cresyl violet histochemistry. A significant reduction in ADC values within the cortex below the injury site by 0.5 days after surgery was observed. Between 5 and 14 days the ADC values recovered to control levels. ADC changes were also observed in the contralateral cortex at 0.5, 1 and 5 days. The decrease in ADC observed at the early time points suggested cytotoxic edema, whereas the recovery to control levels at later time points suggested infarct formation. This model of brain injury resulted in progressive but relatively slow formation of a pan-necrotic infarct within 14 days. In particular, substantial amounts of cell death were not observed until 2 days after surgery. Overall, the quantitative and histological measures of this lesion are consistent with those observed for an ischemic type of injury, however, the time course of these lesions' development are consistent with other models of traumatic brain injury. Our data demonstrates that DWI is a highly sensitive metric for ischemic-type damage that results from brain injury.

Animals↗
PubMed2001

Magnetic resonance imaging predicts neuropathology from soman-mediated seizures in the rodent.

Intoxication by the organophosphate compound soman causes prolonged seizures that lead to neuropathology in the brain. This MRI-based study describes the temporal and spatial evolution of brain pathology that follows soman-induced convulsions. We observed significant decreases in apparent diffusion coefficients (ADC; 23% below control) of the hippocampus and thalamus by 12 h after soman treatment. The ADC then returned to near normal values in all regions at 24 h but declined again during the next 7 days. These data suggest that the initial cellular degradation may be resolved but is ultimately followed by regional cellular remodeling. T2 relaxation values declined significantly at 12 h (37% decrease) returning to near normal values by 24 h. These data lend detail to the model suggesting that injured tissues experience an edematous influx that is resolved by 24 h. The imaging data was fully supported by histopathological comparisons where moderate cell loss and swelling within the hippocampus and piriform cortex was observed. This is the first report providing excellenttemporal and spatial resolution of emerging soman-mediated, seizure-induced neuropathology using MRI with histological correlation.

Amygdala↗
PubMed2001

A reliable method for measurement and normalization of pediatric hippocampal volumes.

A robust standardized method for segmentation, quantification, and normalization of pediatric hippocampal volumes using magnetic resonance imaging is presented. The method will find application in time course measurements of hippocampal volumes in pediatric patients who suffer from temporal lobe epilepsy and was tested prospectively on six control patients (13-60 mo of age). The un-normalized hippocampal volumes obtained using our segmentation method ranged from 3.85 to 6.38 mL, in agreement with previously published results. Inter- and intraobserver variability of the segmentation method was determined to be 13.3% and 2.8%, respectively. Four different methods of volume normalization were tested. Normalization is required to adjust for age-related increases in hippocampal volume. The normalization approach that seemed to compensate best for growth-related hippocampal volume changes was based on a simple estimation of intracranial volumes. This is the first report of a consistent and reliable method for segmentation and normalization of hippocampi from pediatric patients that can be used to study the progression of neurologic diseases in children.

Adolescent↗
PubMed1998

Intravenously administered cell-permeant calcium buffer decreases evoked synaptic potentials in rat dentate gyrus in vivo.

We examined the effects of the neuroprotective cell-permeant Ca2+ buffer, 2-aminophenol-N,N,O-triacetic acid acetoxymethyl ester (APTRA-AM, 20-40 mg/kg), on synaptically evoked potentials in the dentate gyrus of awake rats. Intravenous APTRA-AM (20 mg/kg) decreased the evoked potentials with peak effects approximately 6 h after infusion, and recovery to control levels by 24 h. Peak decrease in the population spike (PS) amplitude was by 72+/-17% of control, and the excitatory postsynaptic potential (EPSP) slope was decreased by 31+/-12%. APTRA-AM (40 mg/kg), decreased the PS amplitude and EPSP slope by 58+/-7% and 31+/-6% of pre-drug levels, respectively. These effects were qualitatively similar to the presynaptically mediated decreases in synaptic potentials previously demonstrated in vitro with APTRA-AM. These results indicate that the cell-permeant Ca2+ buffer, APTRA-AM, attenuates hippocampal excitability in vivo, most likely by decreasing synaptic neurotransmission.

Animals↗
PubMed1998

Dentate granule cells form novel basal dendrites in a rat model of temporal lobe epilepsy.

Mossy fibre sprouting and re-organization in the inner molecular layer of the dentate gyrus is a characteristic of many models of temporal lobe epilepsy including that induced by perforant-path stimulation. However, neuroplastic changes on the dendrites of granule cells have been less-well studied. Basal dendrites are a transient morphological feature of rodent granule cells during development. The goal of the present study was to examine whether granule cell basal dendrites are generated in rats with epilepsy induced by perforant-path stimulation. Adult Wistar rats were stimulated for 24 h at 2 Hz and with intermittent (1/min) trains (10 s duration) of single stimuli at 20 Hz (20 V, 0.1 ms) delivered 1/min via an electrode placed in the angular bundle. The brains of these experimental rats and age- and litter-matched control animals were processed for the rapid Golgi method. All rats with perforant-path stimulation displayed basal dendrites on many Golgi-impregnated granule cells. These basal dendrites mainly originated from their somata at the hilar side and then extended into the hilus. Quantitative analysis of more than 800 granule cells in the experimental and matched control brains showed that 6-15% (mean=8.7%) of the impregnated granule cells have spiny basal dendrites on the stimulated side, as well as the contralateral side (mean=3.1%, range=2.9-3.9%) of experimental rats, whereas no basal dendrites were observed in the dentate gyrus from control animals. The formation of basal dendrites appears to be an adaptive morphological change for granule cells in addition to the previously described mossy fibre sprouting, as well as dendritic and somatic spine formation observed in the dentate gyrus of animal and human epileptic brains. The presence of these dendrites in the subgranular region of the hilus suggests that they may be postsynaptic targets of the mossy fibre collaterals.

Animals↗
PubMed1993

Increased propensity for nonsynaptic epileptiform activity in immature rat hippocampus and dentate gyrus.

1. Low-[Ca2+] bursting was studied in hippocampal slices from immature and adult rats to test the hypothesis that the increased seizure susceptibility of the immature brain involves nonsynaptic mechanisms. Extracellular recordings were obtained from area CA1 of the hippocampus and from the dentate gyrus in slices from rats 6-9 days old (1 wk), 11-15 days old (2 wk), 19-23 days old (3 wk), and > 60 days old (adult). These slices were exposed to a low-[Ca2+] solution that included the calcium chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), and the excitatory amino acid antagonists, 6,7-dinitroquinoxaline-2,3-dione (DNQX) and DL-2-amino-5-phosphonopentanoic acid (AP-5). They were also exposed to a hyposmolar low-[Ca2+] solution (diluted with 20% H2O by volume), which induced or intensified the bursting. The propensity for nonsynaptic bursting and the characteristics of the bursts were compared between age groups. 2. The 1-wk group showed no bursting activity under any treatment condition in either CA1 or the dentate gyrus. Bursting occurred more frequently in the 2- and 3-wk groups than in the adult group in both CA1 and the dentate gyrus. 3. In CA1 the duration of the bursts was longer in the 2- and 3-wk groups as compared with the adult group. The number of population spikes per burst was also higher in slices from immature rats in dilute low-[Ca2+] solution. These findings demonstrate that nonsynaptic bursting in area CA1 is more robust in tissue from immature rats than adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures.

In situ hybridization methods were used to determine if glutamic acid decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate gyrus are vulnerable to seizure-induced damage in a model of chronic seizures. Sprague-Dawley rats were injected intraperitoneally with pilocarpine, and the hippocampal formation was studied histologically at 1, 2, 4, and 8 week intervals after pilocarpine-induced seizures. In situ hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe, demonstrated a substantial decrease in the number of GAD mRNA-containing neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats as compared to controls at all time intervals. Additional neuronanatomical studies, including cresyl violet staining, neuronal degeneration methods, and histochemical localization of glial fibrillary acidic protein, suggested that the decrease in the number of GAD mRNA-containing neurons was related to neuronal loss rather than to a decrease in GAD mRNA levels. The loss of GAD mRNA-containing neurons in the hilus contrasted with the relative preservation of labeled putative basket cells along the inner margin of the granule cell layer. Quantitative analyses of labeled neurons in three regions of the dentate gyrus in the 1 and 2 week groups showed statistically significant decreases in the mean number of GAD mRNA-containing neurons in the hilus of both groups of experimental animals. No significant differences were found in the molecular layer or the granule cell layer, which included labeled neurons along the lower margin of the granule cell layer. The results indicate that, in this model, a subpopulation of GAD mRNA-containing neurons within the dentate gyrus is selectively vulnerable to seizure-induced damage. Such differential vulnerability appears to be another indication of the heterogeneity of GABA neurons.

Animals↗
PubMed1992

Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of the mossy fibers.

Morphological data from humans with temporal lobe epilepsy and from animal models of epilepsy suggest that seizure-induced damage to dentate hilar neurons causes granule cells to sprout new axon collaterals that innervate other granule cells. This aberrant projection has been suggested to be an anatomical substrate for epileptogenesis. This hypothesis was tested in the present study with intra- and extracellular recordings from granule cells in hippocampal slices removed from rats 1-4 months after kainate treatment. In this animal model, hippocampal cell loss leads to sprouting of mossy fiber axons from the granule cells into the inner molecular layer of the dentate gyrus. Unexpectedly, when slices with mossy fiber sprouting were examined in normal medium, extracellular stimulation of the hilus or perforant path evoked relatively normal responses. However, in the presence of the GABAA-receptor antagonist, bicuculline, low-intensity hilar stimulation evoked delayed bursts of action potentials in about one-quarter of the slices. In one-third of the bicuculline-treated slices with mossy fiber sprouting, spontaneous bursts of synchronous spikes were superimposed on slow negative field potentials. Slices from normal rats or kainate-treated rats without mossy fiber sprouting never showed delayed bursts to weak hilar stimulation or spontaneous bursts in bicuculline. These data suggest that new local excitatory circuits may be suppressed normally, and then emerge functionally when synaptic inhibition is blocked. Therefore, after repeated seizures and excitotoxic damage in the hippocampus, synaptic reorganization of the mossy fibers is consistently associated with normal responses; however, in some preparations, the mossy fibers may form functional recurrent excitatory connections, but synaptic inhibition appears to mask these potentially epileptogenic alterations.

Action Potentials↗
PubMed1992

Osmolality and nonsynaptic epileptiform bursts in rat CA1 and dentate gyrus.

In several clinical situations, such as hyposmolar states and hypoxia-ischemia, reductions in the size of the extracellular space are associated with increased seizure susceptibility. Nonsynaptic interactions provide a likely means of mediating the effect of extracellular space on seizure susceptibility. Synchronous bursting of CA1 hippocampal neurons occurs via nonsynaptic mechanisms in solutions containing very low [Ca2+] and excitatory amino acid antagonists. We tested the hypothesis that lowering the osmolality of the extracellular medium could induce nonsynaptic bursting in the dentate gyrus, even though it is normally resistant to this treatment. Extracellular field potentials were recorded in the dentate gyrus and CA1 area of rat hippocampal slices. In the low-[Ca2+] solution with normal osmolality, bursts of population spikes were recorded from the dentate gyrus in only 7% of the slices, but solutions with decreased osmolality induced bursting in 63%. Corresponding values for the CA1 area were 60 and 73%, respectively. Mannitol, which reversed the hyposmolar state, abolished bursting in both regions. This study demonstrates that reducing the size of the extracellular space by lowering extracellular osmolality can transform a seizure-resistant area into one that exhibits robust epileptiform activity.

Action Potentials↗
PubMed1992

Persistent hyperexcitability in isolated hippocampal CA1 of kainate-lesioned rats.

1. Subcutaneous kainate injection in rats evoked acute seizures and led to cell loss in the hilus and areas CA1 and CA3, which resembled the pattern of hippocampal sclerosis often associated with temporal lobe epilepsy in humans. 2. Simultaneous intra- and extracellular recordings were performed in the stratum pyramidale of area CA1 while stimulating in the stratum radiatum close to the recording electrodes. Responses from control slices consisted of a brief excitatory postsynaptic potential (EPSP) with only one action potential, corresponding to a single extracellular population spike, followed by a clear biphasic inhibitory postsynaptic potential (IPSP). In slices from kainate-treated animals, however, stimulation evoked a prolonged EPSP, which often triggered multiple action potentials corresponding to multiple extracellular population spikes. 3. In slices from kainate-treated animals, the mean amplitude but not the duration of the stimulation-evoked IPSP was reduced. The extent of the kainate-induced loss of inhibition in area CA1 was highly variable. 4. Low concentrations of bicuculline in control slices led to a moderate hyperexcitability, which consisted of multiple population spikes and mirrored the responses observed in slices from kainate-treated animals in normal ACSF. Prolonged application of 10-30 microM bicuculline for > or = 30 min led to a much higher level of hyperexcitability, which was similar in slices from controls and kainate-treated rats. These findings are consistent with the hypothesis that the hyperexcitability of CA1 pyramidal neurons following kainate treatment is mainly due to decreased GABAA-receptor-mediated inhibition and that the loss of inhibition is only partial.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The effects of serotonergic compounds on evoked responses in the dentate gyrus and CA1 region of the hippocampal formation of the rat.

The effects of serotonin (5-HT), the 5-HT1A receptor subtype agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor subtype agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on electrophysiological responses in the dentate gyrus and area CA1 were examined in the in vitro hippocampal slice preparation. Superfusion of either serotonin or 8-OH-DPAT in the bath was found to inhibit population responses in a dose-dependent manner in both regions, with a greater effect in the CA1. The effects of 8-OH-DPAT in both regions were attenuated significantly by the serotonergic antagonist methysergide, as were the effects of 5-HT on the population spike in the CA1. The application of DOI did not produce statistically significant effects in either region. These findings support an inhibitory role for the 5-HT1A receptor in both area CA1 and the dentate gyrus.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Osmolality-induced changes in extracellular volume alter epileptiform bursts independent of chemical synapses in the rat: importance of non-synaptic mechanisms in hippocampal epileptogenesis.

The contribution of non-synaptic mechanisms to the seizure susceptibility of rat CA1 hippocampal pyramidal cells was examined in vitro by testing the effects of osmolality on synchronous neuronal activity, using solutions which blocked chemical synaptic transmission both pre- and post-synaptically. Decreases in osmolality, which shrink the extracellular volume, caused or enhanced epileptiform bursting. Increases in osmolality with membrane-impermeant solutes, which expand the extracellular volume, blocked or greatly reduced epileptiform discharges. Reductions in the extracellular volume, therefore, can enhance synchronization among CA1 hippocampal neurons through non-synaptic mechanisms. Since similar osmotic treatments are known to modify epileptiform discharges in several models of epilepsy, non-synaptic mechanisms are probably more important in hippocampal epileptogenesis than previously realized and may contribute to the high susceptibility of this brain region to epileptic seizures in animals and humans. These data also provide a possible explanation for the observation in humans that decreased plasma osmolality, which can be associated with a wide range of clinical syndromes, leads to seizures.

Action Potentials↗
PubMed1989

Dantrolene-Na (Dantrium) blocks induction of long-term potentiation in hippocampal slices.

Long-term potentiation (LTP) is characterized by a long lasting increase in the efficacy of neurotransmission which may consist of two phases. First an induction phase, with an absolute requirement for post-synaptic activation. Second, a maintenance phase, possibly involving pre-synaptic mechanisms. An essential function for calcium ions in the induction of LTP has been established and a particular emphasis has been placed on the role of N-methyl-D-aspartate (NMDA) receptor activation in gating a postsynaptic influx of calcium. We now report that pharmacological blockade of intraneuronal calcium release with 20 microM dantrolene-sodium (dantrium) completely blocks the induction of LTP in the CA1 region of the rat hippocampal slice. This drug inhibits calcium release from the sarcoplasmic reticulum and also diminishes the rise in intraneuronal calcium ion concentrations elicited by NMDA receptor activation in cultured CA1 pyramidal cells. Dantrolene does not block NMDA gated membrane currents or voltage activated Ca2+ currents in these cells. We suggest that release of intraneuronal calcium, rather than calcium influx may be the critical post-synaptic feature underlying LTP induction. We do not however exclude a pre-synaptic involvement in the specificity and/or maintenance of long-term potentiation.

Action Potentials↗
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↗