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PubMed2006

Comparison of manual tracing versus a semiautomatic radial measurement method in temporal lobe MRI volumetry for pharmacoresistant epilepsy.

INTRODUCTION: The aim of this study was to test a modified radial semiautomated volumetry technique (radial divider technique, RDT) versus the manual volumetry technique (MVT) for proportionality of temporal subvolumes in 30 patients with drug-resistant temporal lobe epilepsy. METHODS: Included in the study were 30 patients (15 female, 15 male; mean age 39.6 years) with pharmacoresistant epilepsy (mean duration 26.6 years). MRI studies were performed preoperatively on a 1.5-T scanner. All image processing steps and volume measurements were performed using ANALYZE software. The volumes of six subregions were measured bilaterally; these included the superior temporal gyrus (STG), middle + inferior temporal gyrus (MITG), fusiform gyrus (FG), parahippocampal gyrus (PHG), amygdala (AM), and hippocampus (HP). Linear regression was used to investigate the relationship between the comparable subvolumes obtained with MVT and RDT. RESULTS: Very high correlations (R (2) >0.95) between RDT and MVT were observed for the STG + MITG and the STG + MITG + FG, but low correlations for the PHG subvolumes and the combined PHG + HP + AM subvolumes. These observations were independent of the side of the pathology and of hemisphere. CONCLUSION: The two measurement techniques provided highly reliable proportional results. This series in a homogeneous group of TLE patients suggests that the much quicker RDT is suitable for determining the volume of temporolateral and laterobasal temporal lobe compartments, of both the affected and the non-affected side and the right and left hemisphere.

Adolescent↗

PubMed1998

Intra- and interobserver variability of MRI-based volume measurements of the hippocampus and amygdala using the manual ray-tracing method.

We studied the intra- and interobserver variability of volume measurments of the hippocampus (HC) and the amygdala as applied to the detection of HC atrophy in patients with complex partial seizures (CPE), measuring the volumes of the HC and amygdala of 11 normal volunteers and 12 patients with presumed CPE, using the manual ray-tracing method. Two independent observers performed these measurements twice each using home-made software. The intra- and interobserver variability of the absolute volumes and of the normalised left-to-right volume differences (deltaV) between the HC (deltaV(HC)), the amygdala (deltaV(A)) and the sum of both (deltaV(HCA)) were assessed. In our mainly right-handed normals, the right HC and amygdala were on average 0.05 and 0.03 ml larger respectively than on the left. The interobserver variability for volume measurements in normal subjects was 1.80 ml for the HC and 0.82 ml for the amygdala, the intraobserver variability roughly one third of these values. The interobserver variability coefficient in normals was 3.6% for deltaV(HCA), 4.7% for deltaV(HC) and 7.3% for deltaV(A). The intraobserver variability coefficient was 3.4% for deltaV(HCA), 4.2% for deltaV(HC) amd 5.6% for deltaV(A). The variability in patients was the same for volume differences less than 5% either side of the interval for normality, but was higher when large volume differences were encountered, is probably due to the lack of thresholding and/or normalisation. Cutoff values for lateralisation with the deltaV were defined. No intra- or interobserver lateralisation differences were encountered with deltaV(HCA) and deltaV(HC). From these observations we conclude that the manual ray-tracing method is a robust method for lateralisation in patients with TLE. Due to its higher variability, this method is less suited to measure absolute volumes.

Adolescent↗

PubMed2000

Evaluation of ictal brain SPET using statistical parametric mapping in temporal lobe epilepsy.

An automated voxel-based analysis of brain images using statistical parametric mapping (SPM) is accepted as a standard approach in the analysis of activation studies in positron emission tomography and functional magnetic resonance imaging. This study aimed to investigate whether or not SPM would increase the diagnostic yield of ictal brain single-photon emission tomography (SPET) in temporal lobe epilepsy (TLE). Twenty-one patients (age 27.14 +/- 5.79 years) with temporal lobe epilepsy (right in 8, left in 13) who had a successful seizure outcome after surgery and nine normal subjects were included in the study. The data of ictal and interictal brain SPET of the patients and baseline SPET of the normal control group were analysed using SPM96 software. The t statistic SPM¿t¿ was transformed to SPM¿Z¿ with various thresholds of P<0.05, 0.005 and 0.001, and corrected extent threshold P value of 0.05. The SPM data were compared with the conventional ictal and interictal subtraction method. On group comparison, ictal SPET showed increased uptake within the epileptogenic mesial temporal lobe. On single case analysis, ictal SPET images correctly lateralized the epileptogenic temporal lobe in 18 cases, falsely lateralized it in one and failed to lateralize it in two as compared with the mean image of the normal group at a significance level of P<0.05. Comparing the individual ictal images with the corresponding interictal group, 15 patients were correctly lateralized, one was falsely lateralized and four were not lateralized. At significance levels of P<0.005 and P<0.001, correct lateralization of the epileptogenic temporal lobe was achieved in 15 and 13 patients, respectively, as compared with the normal group. On the other hand, when comparison was made with the corresponding interictal group, only 7 out of 21 patients were correctly lateralized at the threshold of P<0.005 and five at P<0.001. The result of the subtraction method was close to the single case analysis on SPM at P<0.05. However, at higher thresholds (P<0.005 and 0.001) the subtraction method was comparable to the SPM results only when individual ictal images were compared with the normal control group, and not when comparison was with the interictal group. It is concluded that SPM is an alternative diagnostic method for the localization or lateralization of the seizure focus in temporal lobe epilepsy and that interictal SPET could be omitted if a normal brain SPET database were to be established. The medical cost of seizure localization would thereby be reduced.

Adolescent↗

PubMed2006

GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus.

The gamma amino butyric acid (GABA) transporters GAT-1 and GAT-3 were localized by immunohistochemistry in hippocampi removed for the control of medically intractable temporal lobe epilepsy (TLE). The study aimed to determine the relationship of GABA transporter expression to known patterns of hippocampal hyperexcitability and extracellular GABA levels. GAT-1 was localized in axon terminals and small neuronal cell bodies, and in non-sclerotic hippocampi was strongly expressed throughout all regions of the hippocampal formation. In the epileptogenic hippocampus exhibiting Ammon's horn sclerosis, immunoreactivity was reduced in the sclerotic regions CA3 and CA1, and around the cell bodies of dentate granule cells, but was increased along granule cell dendrites. GAT-3 was weakly expressed, if at all, in non-sclerotic hippocampi, but more prominently expressed in sclerotic hippocampi. GAT-3 expression was confined to cells resembling protoplasmic astrocytes, which were located in regions of relative neuronal sparing such as the dentate gyrus and hilus of the sclerotic hippocampus. The reduction in GAT-1 around granule cells in the sclerotic hippocampus could explain the prolonged GABA responses in this region. The loss of GAT-1 (a marker of GABAergic terminals) would also suggest a reduced GABAergic input to the granule cells, thus facilitating hyperexcitability. The increased GAT-3 expression in astrocytes in regions of relative neuronal sparing in the sclerotic hippocampus may be related to the overall low levels of extracellular GABA observed in the sclerotic hippocampus and their increased excitability.

Adolescent↗

PubMed2001

A grading system for hippocampal sclerosis based on the degree of hippocampal mossy fiber sprouting.

In patients suffering from temporal lobe epilepsy (TLE) a highly variable degree of hippocampal sclerosis (HS) can be observed. For standard neuropathological evaluation after hippocampal resection, neuronal cell loss in the hippocampal subareas is assessed (Wyler score 0-4) [Wyler et al. (1992) J Epilepsy 5: 220-225]. Other marked morphological changes in the sclerotic hippocampus are gliosis and loss of mossy fibers in the hilus and mossy fiber sprouting in the supragranular layer. In this study we quantified changes in mossy fiber density using Timm's stain in resected hippocampal tissue from patients with various degrees of sclerosis. We found that tissue specimens from patients without sclerosis (W0) show almost no mossy fiber sprouting. Patients with moderate sclerosis show sprouting without fiber loss in the hilus, whereas specimens from patients with severe sclerosis show sprouting as well as fiber loss in the hilus. Thus, analysis of mossy fiber abundance in hilus and supragranular layer by the rapid and simple Timm's stain is a sensitive measure for hippocampal sclerosis. It provides a reliable rapid tool for neuropathological evaluation, even if the tissue only contains dentate gyrus due to the sectioning procedure.

Axons↗

PubMed2005

Choice of either beta-catenin or Groucho/TLE as a co-factor for Xtcf-3 determines dorsal-ventral cell fate of diencephalon during Xenopus development.

Co-repressor Groucho/Transducin-Like Enhancer of split (TLE) interacts with transcription factors that are expressed in the central nervous system (CNS), and regulates transcriptional activities. In this study, we examined the contribution of Groucho/TLE to CNS development in Xenopus. The functional inhibition of Groucho/TLE using the WRPW motif as a competitor resulted in the conversion of the ventral cell into the dorsal fate in the prospective diencephalon. We also found that the neural plate was expanded laterally without inhibiting neural crest development. In tailbud, the disturbance of trigeminal ganglion development was observed. These observations allow us to conclude that Groucho/TLE plays important roles in the induction and patterning of distinct CNS territories. We found that Xtcf-3 is involved in some of the patterning in these territories. We generated the variant of Xtcf-3, Xtcf-3BDN-, which is suspected to interfere with the interaction between endogenous Groucho/TLE and Xtcf-3. The transcriptional activation of the Xtcf-3-target genes in response to endogenous Wnt/beta-catenin signaling by the overexpression of Xtcf-3BDN- led to a reduction of the ventral diencephalon. This result indicates that transcriptional repression by the Groucho/TLE-Xtcf-3 complex is important for ventral diencephalon patterning. This idea is supported by the finding that the overexpression of the dominant-negative form of Xtcf-3 or axil causes the expansion of the ventral diencephalon. Based on these data, we propose that the localized activation of Wnt/beta-catenin signaling, which converts Tcf from a repressor to an activator, is required for the establishment of dorsal-ventral patterning in the prospective diencephalon.

Amino Acid Motifs↗

PubMed2006

Co-factors and co-repressors of Engrailed: expression in the central nervous system and cerci of the cockroach, Periplaneta americana.

In the larval cockroach (Periplaneta americana), knockout of Engrailed (En) in the medial sensory neurons of the cercal sensory system changes their axonal arborization and synaptic specificity. Immunocytochemistry has been used to investigate whether the co-repressor Groucho (Gro; vertebrate homolog: TLE) and the co-factor Extradenticle (Exd; vertebrate homolog: Pbx) are expressed in the cercal system. Gro/TLE is expressed ubiquitously in cell nuclei in the embryo, except for the distal pleuropodia. Gro is expressed in all nuclei of the thoracic and abdominal central nervous system (CNS) of first instar larva, although some neurons express less Gro than others. Cercal sensory neurons express Gro protein, which might therefore act as a co-repressor with En. Exd/Pbx is expressed in the proximal portion of all segmental appendages in the embryo, with the exception of the cerci. In the first instar CNS, Exd protein is expressed in subsets of neurons (including dorsal unpaired medial neurons) in the thoracic ganglia, in the first two abdominal ganglia, and in neuromeres A8-A11 of the terminal ganglion. Exd is absent from the cerci. Because Ultrabithorax/Abdominal-A (Ubx/Abd-A) can substitute for Exd as En co-factors in Drosophila, Ubx/Abd-A immunoreactivity has also been investigated. Ubx/Abd-A immunostaining is present in abdominal segments of the embryo and first instar CNS as far caudal as A7 and faintly in the T3 segment. However, Ubx/Abd-A is absent in the cerci and their neurons. Thus, in contrast to its role in Drosophila segmentation, En does not require the co-factors Exd or Ubx/Abd-A in order to control the synaptic specificity of cockroach sensory neurons.

Animals↗

PubMed2004

Hippocampal microdialysis during spontaneous intraoperative epileptiform activity.

BACKGROUND: The actual mechanisms underlying human hippocampal epileptogenicity, a process ultimately mediated by neurochemical events, remains to be fully elucidated. We submit early insight data regarding microdialysis (MD) recovery of the neuroactive amino acids glutamate, aspartate and gamma-aminobutyric acid (GABA) from the intraoperative and intact, spontaneously epileptiform human hippocampus. METHOD: Generally anaesthetised temporal lobe epilepsy (TLE) patients (N=7) undergoing therapeutic and anatomically standardised resective surgery were also subjected to ipsilateral anterior hippocampal MD with concomitant hippocampal electrocorticography (ECoG). Recovered 10-min dialysate samples were quantified for glutamate, aspartate and GABA using high-performance liquid chromatography; corresponding ECoG data was assessed for epileptiform activity (EA); mesial resection tissue was postoperatively examined and graded for hippocampal sclerosis. FINDINGS: Mean 'Sample 3' dialysate absolute recovery of glutamate, aspartate and GABA from hippocampi with minimal EA (N=5) was ( micro M+/-SEM): 6.406+/-2.143, 0.600+/-0.215, and 0.357+/-0.093, respectively. In contrast, 'Sample 3' dialysate absolute glutamate, aspartate and GABA levels ( micro M) from the hippocampi of two patients with vigorous EA were: 101.099 and 211.861, 21.860 and 14.482, and 4.241 and 4.817, respectively. Mesial resection tissue in all cases demonstrated hippocampal sclerosis, though the histopathological degree of sclerosis varied between patients. INTERPRETATION: These preliminary intraoperative findings suggest that dialysate glutamate, aspartate, and GABA levels from the sclerotic anterior hippocampus likely reflects the functional status of the sampled tissue - i.e., lower levels of these neuroactive amino acids are to be expected during quiescent or minimal EA versus considerably higher levels corresponding to vigorous EA.

Adult↗

PubMed1987

Radioiodination and 125I-labeled peptide mapping of proteins on nitrocellulose membranes.

A rapid procedure for generating dozens of 125I-labeled peptide maps from a protein band excised from a single lane of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel has been developed. Proteins, which can be rapidly purified by 2 X SDS-PAGE separation, are electroblotted onto nitrocellulose paper (NCP) and located by aqueous naphthol blue-black staining. All subsequent steps of radioiodination, and enzyme or chemical cleavage, are carried out on the NCP making it possible to test a variety of cleavage reagents on the same protein sample. The resultant peptidic residues, which can be separated by thin-layer electrophoresis-thin-layer chromatography (2D TLE-TLC), SDS-PAGE, or HPLC, can be used in comparative studies or they can be recovered for further structural and immunological analyses.

Bacterial Proteins↗

PubMed1989

Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy.

It has been hypothesized on the basis of animal models of epilepsy that abnormal neural activity in epilepsy may be related to reorganized neural circuits that facilitate epileptogenesis. Little evidence of this was available for human epilepsy. This paper provides the first evidence of such reorganization of a hippocampal seizure focus in human temporal lobe epilepsy (TLE). This reorganization involves the selective loss of somatostatin and neuropeptide Y immunoreactive interneurons, and axonal sprouting of other neuropeptide Y neurons and dynorphin-A immunoreactive granule cells. This set of changes is not exactly like those that are reported in animal models.

Dynorphins↗

PubMed1978

The relationship of fatty acid composition and surface activity of lung extracts.

Male weanling rats were fed fat-free diets supplemented with 4% (w/w) safflower oil (control) or 4% tripalmitin (essential fatty acid (EFA) deficient) for 14 weeks. Whereas the amount of lecithin in lung lavage material remained unchanged, lung lavage lecithin from EFA-deficient rats contained significantly less palmitic acid (61.4 +/- 2.0% vs. 77.4 +/- 5.8%, P less than 0.01) than that from controls. Surface tension vs. area hysteresis loops were obtained for total lipid extracts (TLE) of lung lavage fluid, intra- and extra-cellular lipoprotein fractions (IBI and IBE) and lipid extracts of those lipoprotein fractions (LBI and LBE). A significant increase in minimal surface tension (gammamin) was found for all samples obtained from EFA-deficient rats as compared to controls. Refeeding of diets containing safflower oil for 7-14 days reversed these changes. Air pressure-volume curves on degassed, excised lungs indicated that greater pressure is required to maintain a given lung volume in EFA-deficient rats. These results support the hypothesis that the fatty acid composition of pulmonary surfactant lecithins is a major determinant of the surface activity of lung extracts.

Animals↗

PubMed1994

An investigation on the antigenic cross-reactivity of Calloselasma rhodostoma (Malayan pit viper) venom hemorrhagin, thrombin-like enzyme and L-amino acid oxidase using enzyme-linked immunosorbent assay.

Indirect ELISA shows that the antibodies to Calloselasma rhodostoma venom hemorrhagin (CR-HMG), thrombin-like enzyme (CR-TLE) and L-amino acid oxidase (CR-LAAO) exhibited strong to moderate cross-reactions with most crotalid and viperid venoms, but only anti-CR-LAAO cross-reacted with the elapid venoms. However, the indirect ELISA failed to detect some antigenic similarities demonstrable by cross-neutralization study. The double-sandwich ELISA for the three anti-C. rhodostoma venom components exhibited a much lower level of cross-reactions than the indirect ELISA.

Amino Acid Oxidoreductases↗

PubMed1994

Quantification of opiate receptors in two patients with mesiobasal temporal lobe epilepsy, before and after selective amygdalohippocampectomy, using positron emission tomography.

Using PET, reduced glucose metabolism (rCMRglu) and increased binding of the mu opiate receptor ligand 11C-carfentanil have been demonstrated in lateral temporal cortex overlying mesial temporal epileptic foci. Binding of the non-specific opiate receptor ligand 11C-diprenorphine (DPN) to lateral temporal cortex has not shown consistent asymmetries. We measured rCMRglu with 18F-FDG and binding of 11C-diprenorphine in two patients with temporal lobe epilepsy (TLE) before and 5 months after selective amygdalo-hippocampectomy (both patients were seizure-free post-operatively). Pre-operatively, in both patients rCMRglu was decreased in mesial temporal lobe (MTL) (asymmetry index AI = -9.1 and 9.0) ipsilateral to the EEG focus. A more marked reduction was seen in ipsilateral lateral temporal cortex (LTC) (AI = -32.0 and 18.9). DPN binding was reduced in MTL and LTC (AI MTL = -9.3 and 16.2; AI LTC = -8.0 and 5.5) ipsilateral to the focus, but was within 2 SD of the normal range. Post-operatively, the reduction of rCMRglu in LTC was accentuated in one patient and decreased in the other (AI = -23.1 and 45.7) while there was a further reduction of DPN binding in LTC in both patients (AI = -27.8 and 9.8). These preliminary results in only two patients are compatible with downregulation of opiate receptors in LTC after removal of the epileptic focus or post-operative neuronal dysfunction.

Adult↗

PubMedDate not supplied

Epilepsy, psychosis and schizophrenia.

A connection between epilepsy, especially temporal lobe (psychomotor, limbic) epilepsy (TLE) and schizophrenia has been proposed by a number of investigators. The evidence both supporting and challenging this widespread idea is reviewed, and several hypotheses are considered that may account for the higher incidence of this form of epilepsy and of schizophrenic psychoses after adolescence.

Electroencephalography↗

PubMed2006

Interactions between NTS2 neurotensin and opioid receptors on two nociceptive responses assessed on the hot plate test in mice.

The intracerebroventricular administration of the tridecapeptide neurotensin (NT) produces strong analgesic effects in tests evaluating acute pain. We investigated whether these effects are mediated by the opioid receptors. In the hot plate test, the NT receptors agonist NT1 (N(alpha)Me-Arg-Lys-Pro-Trp-Tle-Leu), s.c. injected (0.3-3 mg/kg), increased paw licking and jump latencies. These effects were inhibited by the NTS2 antagonist levocabastine (2.5 mg/kg, i.p.) but not by the selective NTS1 antagonist SR48692 (3 mg/kg, i.p.). The opioid receptor antagonist naloxone did not modify (up to the dose of 4.5 mg/kg, s.c.) the NT1 effect on licking, but abolished the increase in the jump latency (from the dose of 1.5 mg/kg). In mice made tolerant to the analgesic effect of morphine (2 mg/kg, s.c.) by previous morphine injections (32 mg/kg, s.c., twice a day, 4 days), NT1 maintained its effect on licking, but its effect on jump latency was suppressed. Levocabastine (up to the dose of 4.5 mg/kg) failed to antagonize the effects of morphine (2 mg/kg, s.c.) on both licking and jump latencies. In mice made tolerant to the analgesic effect of NT1 (0.3 mg/kg, s.c.) by previous NT1 injections (3 mg/kg, s.c., twice a day, 4 days) morphine maintained its analgesic effects both on licking and jumping latencies. We can conclude that neurotensinergic and opioidergic transmissions are functionally independent as regards the licking response. However, in the jump response, neurotensinergic transmission seems to regulate opioidergic transmission, inducing its stimulation.

Analgesia↗

PubMed2004

Role of kinin B1 and B2 receptors in the development of pilocarpine model of epilepsy.

The tissue sclerosis found in epilepsy of limbic origin is characterized by shrunken gliotic hippocampus, granule cell loss in the dentate gyrus and extensive pyramidal cell loss in Ammon's horn. Evidence has indicated that sprouting of dentate granule cell axons into the inner molecular layer of the dentate gyrus is related to hyperexcitability. Trying to understand the role of kinin B1 and B2 receptors in the physiopathology of temporal lobe epilepsy (TLE), the present work was delineated to study the development of the epilepsy model induced by pilocarpine in B1 and B2 knockout mice (B1KO and B2KO, respectively). Behavior parameters, cell death and mossy fiber sprouting were analyzed. B1KO mice showed increased latency for the first seizure, associated to a decreased frequency of spontaneous seizures, when compared with wild-type mice. In addition, B1KO mice showed less cell death in all hippocampal formation associated to a reduced grade of mossy fiber sprouting. Furthermore, B2KO mice presented minor duration of the silent period and an increased frequency of spontaneous seizures, when compared with wild-type mice. B2KO and their control lineage showed similar pattern of cell death in the hippocampus, which was very intense when compared with saline-treated animals. The mossy fiber sprouting was also increased in B2KO mice, when compared to wild-type mice and saline-treated animals. Taken together, these data suggest a deleterious effect for kinin B1 receptor and a protective effect for kinin B2 receptor during the development of the temporal lobe epilepsy.

Animals↗

PubMed2004

Reduction of brain injury by antithrombotic agent acutobin after middle cerebral artery ischemia/reperfusion in the hyperglycemic rat.

In vivo magnetic resonance imaging (MRI) was used to observe the effect of acutobin, a purified thrombin-like enzyme (TLE), isolated from the snake venom of Deinagkistrodon acutus, on MRI-detected brain lesion volume and tissue perfusion deficit in a hyperglycemic rat right middle cerebral artery occlusion/reperfusion (MCAO/R) model. Acutobin (0.75 U/ml) was intravenously injected with a dosage of 2.5 U/kg body weight 30 min after MCAO (MCAO duration=60 min) and again 24 h after reperfusion. Multislice diffusion weighted imaging (DWI) and single-slice dynamic bolus tracking gradient echo (GE) imaging were sequentially acquired before and after MCAO/R. DWI-detected lesion volume was significantly (p<0.05) reduced by 24-31% from 350+/-45, 369+/-45 and 374+/-36 mm(3) in the saline-treated group to 239+/-17, 282+/-26 and 259+/-32 mm(3) at 3, 4 and 24 h after reperfusion in the acutobin-treated group, respectively. Residual cerebral blood flow (CBF) in the right hemisphere recovered and remained at approximately 80% of normal perfusion over the measurement period in the acutobin-treated group, compared to approximately 40% in the saline-treated group. Mortality at 1 week after MCAO/R in the acutobin-treated group was significantly lower (25% mortality) than the saline control group (85% mortality). Our results indicate that acutobin improves brain tissue perfusion and reduces infarct volume and mortality in the hyperglycemic rat MCAO/R model.

Animals↗

PubMed2004

In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted MRI during lithium-pilocarpine-induced status epilepticus in the rat.

Temporal lobe epilepsy (TLE) is associated with febrile convulsions and childhood status epilepticus (SE). Since the initial precipitating injury, triggering epileptogenesis, occurs during this SE, we aimed to examine the metabolic and morphological cerebral changes during the acute phase of experimental SE noninvasively. In the rat lithium-pilocarpine model of SE, we performed quantified T(2)- and isotropic-diffusion-weighted (DW) magnetic resonance imaging (MRI) at 3 and 5 h of SE and acquired single-voxel (1)H MR spectra at 2, 4 and 6 h of SE. T(2) was globally decreased, most pronounced in the amygdala (Am) and piriformic cortex (Pi), in which also a significant decrease in apparent diffusion coefficient (ADC) was found. In contrast, ADC values increased transiently in the hippocampus (HC) and thalamus (Th). MR spectra showed a decrease in N-acetylaspartate (NAA) and choline (Cho) and an increase of lactate in a hippocampal voxel. The T(2) decrease, attributed to raised deoxyhemoglobin, and the presence of lactate both indicate a mismatch between oxygen demand and delivery. The ADC decrease, indicative of excitotoxicity, confirms that the amygdala and piriformic cortex are particularly vulnerable to lithium-pilocarpine-induced seizures. The transient ADC increase in the thalamus may reflect the breakdown of the blood-brain barrier (BBB), which is shown to occur in this region at these time points. Neuronal damage and failure of energy-dependent formation of NAA are likely causes of an observed decrease in NAA, while the decrease in Cho is possibly due to depletion of the cholinergic system. This study illustrates that relative hypoxia, excitotoxicity and concomitant neuronal damage associated with SE can be probed noninvasively with MR. These pathological phenomena are the first to contribute to the pathophysiology of spontaneous recurrent seizures in a later stage in this animal model.

Animals↗