Search PubMed⌕ Search

Biomedical subjects

J Schramm

Publications and source records attributed to J Schramm.

At least 55 records · Page 3Linked to original sources
PubMed2001

Mutational analysis of TSC1 and TSC2 genes in gangliogliomas.

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of glial and neuronal elements, the focal nature and their differentiated phenotype and benign biological behaviour suggest an origin from a developmentally compromised or dysplastic precursor lesion. The present study analysed TSC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role in cortical differentiation and growth control. DNA sequence analysis of TSC1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of these polymorphisms was significantly increased in intron 4 (12.5%) and exon 41 (15%) compared to control individuals (8.1 and 6.5%, respectively, n = 100). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in this gene. Laser microdissection and harvesting of individual neuronal and glial elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous polymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.

Brain Neoplasms↗
PubMed2001

Long-term seizure outcome and antiepileptic drug treatment in surgically treated temporal lobe epilepsy patients: a controlled study.

PURPOSE: To evaluate the long-term impact of surgical treatment on seizure outcome and antiepileptic drug (AED) use in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Comparison of seizure outcome and AED us in operated-on TLE patients (n=148) and nonsurgically treated TLE patients (n=94) at a baseline visit and a follow-up visit after a mean period of 4.8 years. RESULTS: At follow-up, 44.6% of the surgical patients and 4.3% of the nonsurgical patients had been continuously seizure- free since the baseline visit (including the immediate postoperative period). A further 17.6% of the operated-on and 3.2% of the not operated-on patients had been seizure-free for at least the previous year; 37.8% of the surgical and 92.5% of the nonsurgical patients had had seizures during the previous 12 months (p < 0.001). Of the surgical patients, 8.8% versus none of the nonsurgical patients were AED free at follow-up; 55.4% versus 20.2% were receiving monotherapy, and 35.8% versus 79.8% were receiving polytherapy (p < 0.001). Mean number of AEDs and mean change in number of AEDs were significantly more favorable in operated-on than in non-operated-on patients. Further subgroup analysis revealed that not only the continuously seizure-free surgical patients, but also the operated-on patients with ongoing seizures took fewer AEDs than their respective non-operated-on counterparts. CONCLUSIONS: This controlled study for the first time provides comprehensive information on long-term seizure outcome and AED use in surgical TLE patients. It shows a more favorable seizure outcome and AED use in the surgically treated patients. The latter holds true even for the not seizure-free patient subgroup.

Adult↗
PubMed2001

Vagus nerve stimulation: clinical experience in a large patient series.

During the last decade, intermittent electrical stimulation of the left cervical vagus nerve was established as a new add-on treatment of drug-resistant seizures. Particularly in Europe, the acceptance of vagus nerve stimulation (VNS) was tentative in the beginning because of unknown mechanisms of action. We report the outcome in a sample of 95 adult patients with drug-resistant seizures who have received implants since 1998. The last available follow-up data are included. Unavoidable medication changes (e.g., intoxication) were accepted to examine VNS under usual clinical conditions. Median percentage of reduction in seizure frequency as compared to baseline was 30%. The seizure responder rate (> or =50% reduction) was 45%. Four patients experienced total release from seizures. Adverse effects were mild in general. Seizure outcome was positively correlated with VNS duration. No potential clinical factor (e.g., syndrome, cause, or lesion) could be identified as an indicator of favorable outcome. Patients with on stimulation-on periods of 30 seconds (standard cycle) had a better outcome than patients with stimulation-on periods of 7 seconds (rapid cycle). During an embedded, randomized, controlled trial, no evidence was found for a differential outcome of initial standard cycle versus initial rapid cycle stimulation conditions. Taking into account the good cost-benefit ratio as well as positive effects on well-being, VNS has to be considered an appropriate strategy for the add-on treatment of drug-resistant seizures, particularly in cases not suitable for epilepsy surgery.

Adult↗
PubMed2001

What factors are related to impairment of cerebrovascular reserve before and after arteriovenous malformation resection? A cerebral blood flow study using xenon-enhanced computed tomography.

OBJECTIVE: To examine the incidence and possible determinants of impaired vascular reserve in arteriovenous malformation (AVM)-affected brain, before and after surgery. METHODS: In a prospective study of 30 patients, the regional cerebrovascular reserve capacity (rCRC) and the vasodilated regional cerebral blood flow (rCBF) were assessed during an acetazolamide challenge, using xenon-enhanced computed tomography, before and after complete AVM resection. Single brain slices at the level of the basal ganglia were examined, and scanning through the AVMs was avoided. Five regions of interest in the AVM-bearing hemisphere were compared with their counterparts in the unaffected hemisphere. Vasodilated rCBF reductions of at least 20% in one or more regions of interest and rCRC values of less than 10 ml/100 g/min were considered to be significant. RESULTS: Ipsilateral vasodilated rCBF was significantly reduced in 17 patients before surgery and 15 patients after surgery. Ipsilateral rCRC was impaired in 14 patients before surgery and 12 patients after surgery. Large AVM size, venous congestion, and AVM-related vascular territories were correlated with impaired vascular reserve in AVM-nonadjacent brain tissue before surgery. Similar correlations were observed after surgery, except that not AVM size but a large number of AVM-supplying vascular territories was correlated. Moreover, the smallest AVMs and those supplied by a single vascular territory, as well as hemorrhage and nonhemorrhagic neurological deficits as presenting symptoms, were correlated with reduced ipsilateral vasodilated rCBF before surgery. Among patients with AVMs and nonhemorrhagic epilepsy, a trend of impaired cerebrovascular reserve was observed. In the only case of postresectional "breakthrough," the preoperative rCRC was not impaired but abnormally high. CONCLUSION: Among the determinants of impaired cerebrovascular reserve, AVM size is already a constituent of current grading scales and decision-making paradigms, whereas factors such as venous congestion have been less closely considered or less obvious but may deserve increased attention in the future. Nonhemorrhagic epilepsy in patients with AVMs may constitute the clinical equivalent of chronic cerebral ischemia in a murine model. Postresectional breakthrough may be partly attributable to individual predisposition to excessive vasoreactivity in the whole brain.

Acetazolamide↗
PubMed2001

Transsylvian keyhole functional hemispherectomy.

OBJECTIVE: To describe the technical steps, advantages, and limitations of a quicker, minimal-exposure, functional hemispherectomy procedure developed from a hemispherical deafferentation technique previously described. METHODS: The surgical approach using the transsylvian/transsulcal passage to the ventricular system, with the anatomic orientation points and key features for planning of the small trepanation, is described. Through a linear incision, a craniotomy (4 x 4 to 4 x 5 cm) is placed over the sylvian fissure. Transsylvian exposure of the circular sulcus allows transcortical exposure of the entire ventricular system, from the frontal horn to the temporal horn encircling the insular cortex. The frontobasal and mesial white matter is disconnected via the intraventricular approach, with a callosotomy. An amygdalohippocampectomy completes the dissection. The experience with 20 patients who were treated using the transsylvian keyhole hemispherectomy technique is summarized. RESULTS: The operation time was significantly shorter (mean, 3.6 h) than with the Rasmussen technique (mean, 6.3 h) and 25% shorter than with the transcortical perisylvian technique (mean, 4.9 h). The proportion of patients requiring blood replacements was lower (15 versus 58%), as was the mean amount of transfused blood. The mean follow-up period was 46 months; 88% of patients were in Engel Outcome Class I, 6% in Class III, and 6% in Class IV. CONCLUSION: The transsylvian keyhole procedure has been demonstrated to further reduce operation time and the need for blood replacement. It is most easily performed in cases with enlarged ventricles or perinatal ischemic cysts and is not recommended for hemimegalencephaly. The immediate seizure relief was satisfying. This minimal-exposure approach seems to be a satisfying alternative among possible functional hemispherectomy procedures.

Adolescent↗
PubMed2001

Fixed and dilated pupils after trauma, stroke, and previous intracranial surgery: management and outcome.

OBJECTIVES: To clarify whether different causative events (trauma, stroke, intracranial surgery), time of intervention, and treatment mode influence outcome, patients with fixed and dilated pupils (FDPs) in a prospective neurosurgical series were evaluated. METHODS: Ninety nine consecutive patients who presented with or developed one or two FDPs, were split into three groups according to the respective aetiology: 46 patients had a trauma, 41 patients a stroke (subarachnoid or intracerebral haemorrhage), and 12 patients had undergone previous elective intracranial surgery. Appropriate therapy was performed depending on the CT findings. Outcome was classified according to the Glasgow outcome scale (GOS). RESULTS: Overall mortality was 75%. In 15% outcome was unfavourable (GOS 2 and 3), and in 10% favourable (GOS 4, 5) at 24 month follow up. No differences in outcome were found between trauma, stroke, and postelective surgery groups. Unilaterally FDP was associated with a better chance of survival (46% v 13%; p<0.01). Age did not correlate with survival, but younger survivors had a significantly better outcome. Patients in whom an intracranial mass was removed surgically had a 42% survival rate, compared with 8% with conservative treatment (p<0.01). Patients with a shorter delay from FDPs to intervention had a better chance of recovery after trauma and previous intracranial surgery (p<0.05). No patient survived better than a vegetative state, if previous FDPs did not become reactive shortly after therapy. If both pupils became reactive on therapy, the chance of survival was 62%. Of these survivors 42% had a favourable outcome. CONCLUSION: Bilateral restoration of pupillary reactivity shortly after therapy is crucial for survival. Surgical evacuation of an intracranial mass, unilateral FDPs, early intervention, and younger age are related to better chances of survival or recovery. The prognosis of patients with FDPs after trauma, stroke, and previous elective intracranial surgery is similar.

Adolescent↗
PubMed2001

Characterization of the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase complex in the human brain.

Although androgen metabolism in the human brain was discovered almost 30 yr ago, conclusive studies on the enzymes involved are still lacking. We therefore investigated 5alpha-reductase and colocalized 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) activity in cerebral neocortex (CX) and subcortical white matter (SC) specimens neurosurgically removed from 44 patients suffering from epilepsy. We could demonstrate the presence of the 5alpha-reductase-3alpha-HSD complex in the biopsies of all patients under investigation. Inhibition experiments with specific inhibitors for 5alpha-reductase type 1 and type 2 revealed strong evidence for the exclusive activity of the type 1 isoform. We detected a significantly higher 5alpha-reductase activity in CX than in SC (P< 0.0001), but no sex-specific differences were observed. Furthermore, we found that, in contrast to liver, only 3alpha-HSD type 2 messenger RNA is expressed in the brain and that its expression is significantly higher in SC than in CX without sex-specific differences. The present study is the first to systematically characterize the 5alpha-reductase-3alpha-HSD complex in the human brain. The lack of sex-specific differences and also the colocalization of both enzymes at all life stages suggest a more general purpose of the complex, e.g. the synthesis of neuroactive steroids or the catabolism of neurotoxic steroids, rather than control of reproductive functions.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

Surgical treatment for neocortical temporal lobe epilepsy: clinical and surgical aspects and seizure outcome.

OBJECT: The goal of this paper was to describe the clinical and surgical aspects of a group of patients suffering from drug-resistant neocortical temporal lobe epilepsy (TLE), as well as seizure outcomes and factors affecting seizure outcomes in these patients. METHODS: This study was based on data prospectively collected and retrospectively evaluated. Sixty-two patients with neocortical TLE constituted the study population. Only patients who underwent corticectomies, lesionectomies, lateral anterior lobe resections, and/or multiple subpial transections were included. The pathological areas resected in these patients could be separated into three groups composed of 35 neoplastic lesions, 23 nonneoplastic lesions, and three nonlesional areas. The mean duration of follow-up review in these patients was 21.9+/-14 months. Outcomes were categorized according to Engel classes. Class I was found in 79% of the patients and Class II in 11%. Invasive presurgical evaluation was performed in 43% of the patients. There were only temporary complications (3.3% surgical and 1.6% neurological) and no deaths. In summary, lesions confirmed on histological examination were rarely found in patients with neocortical TLE. Low-grade tumors were the most commonly found lesions in these patients and the most common tumor was ganglioglioma. Outcome was best for those patients with neoplastic lesions and was independent of the duration of their seizures. Outcome was little influenced by the type of resection performed and was found to be as good as that achieved in patients with mesial TLE. CONCLUSIONS: These results demonstrate that the concept of lateral or neocortical TLE as a distinct entity is useful. Surgery for neocortical TLE can be considered a viable treatment option that is associated with a low morbidity rate and good outcomes.

Adolescent↗
PubMed2001

Is stagnating flow in former feeding arteries an indication of cerebral hypoperfusion after resection of arteriovenous malformations?

OBJECT: The authors' goal in this study was to challenge the proposed mechanism of the occlusive hyperemia theory, in which it is asserted that stagnating flow in the former feeding arteries of cerebral arteriovenous malformations (AVMs) leads to parenchymal hypoperfusion or ischemia, from which postoperative edema and hemorrhage originate. METHODS: Cortical oxygen saturation (SaO2) was measured in 52 patients by using microspectrophotometry in areas adjacent to AVMs before and after resection. The appearance of the former feeding arteries was categorized as normal (Group A); moderately stagnating (Group B); and excessively stagnating (Group C) on postoperative angiographic fast-film series. Patients and SaO2 values were pooled accordingly and compared using analysis of variance and Duncan tests (p < 0.05). Angiographic stagnation times in former feeding arteries were correlated in a linear regression/correlation analysis with SaO2 data (p < 0.05). All values are given as the mean +/- standard deviation. The average median postoperative SaO2 in Group C (15 patients) was significantly higher than in Groups B (17 patients) and A (20 patients) (Group C, 75.2 +/- 8.5; Group B, 67.5 +/- 10.8; Group A, 67.1 +/- 12 %SaO2), as was the average postoperative increase in SaO2 (Group C. 25.9 +/- 14.9; Group B, 14.6 +/- 14; Group A, 11.1 +/- 14 %SaO2). Angiographically confirmed stagnation times were also significantly longer in Group C than in Group B (Group C, 5.6 +/- 2.5; Group B, 1.3 +/- 0.6 seconds). A significant correlation/regression analysis showed a clear trend toward higher postoperative SaO2 levels with increasing stagnation time. CONCLUSIONS: Stagnating flow in former feeding arteries does not cause cortical ischemia, but its presence on angiographic studies is usually indicative of hyperperfusion in the surrounding brain tissue after AVM resection. In the context of the pathophysiology of AVMs extrapolations made from angiographically visible shunt flow to blood flow in the surrounding brain tissue must be regarded with caution.

Adolescent↗
PubMed2000

Serum androgens return to normal after temporal lobe epilepsy surgery in men.

BACKGROUND: Epileptic discharges from the temporal lobe may influence the release of hormones from the hypothalamic-pituitary axis. If epilepsy surgery influences the underlying epileptic disorder one might expect serum hormone concentrations to return to normal following surgery. PATIENTS: Twenty-two men with epilepsy aged 25 to 48 years (mean, 34.9 years) were investigated before surgery and at 3, 6, and 12 months after surgery. Medication (all patients received carbamazepine) was maintained following surgery. METHODS: Hormone measurements included luteinizing hormone, follicle stimulating hormone, estradiol, testosterone, free testosterone, androstenedione, prolactin, dehydroepiandrosterone sulfate, cortisol, growth hormone, and sex hormone-binding globulin. These hormone levels were compared with those of 105 healthy men (mean age, 33.9 years). RESULTS: Fourteen of the 22 patients (63.6%) achieved total seizure control following epilepsy surgery. The 14 patients with successful seizure control entered further analysis. Before surgery these patients' free testosterone and androstenedione concentrations were significantly lower compared with healthy men. In seven of the 14 patients a significant increase of hormone serum concentrations could be demonstrated for testosterone, free testosterone, and androstenedione. Laterality of epileptic focus, enzyme-inducing medication, stress, and the decreasing number of patients during the follow-up did not correlate with the finding of a normalization of serum androgens. PATIENTS without complete seizure control did not show an increase in serum androgen concentrations. CONCLUSION: Successful temporal lobe epilepsy surgery may lead to a normalization of serum androgen concentrations in men with epilepsy.

Adult↗
PubMed2000

[Temporal lobe epilepsy: longitudinal clinical, neuropsychological and psychosocial follow-up of surgically and conservatively managed patients].

Little is known about the differential long-term outcome from surgical and nonsurgical therapy in patients with chronic epilepsy. In the present study, 161 surgically or nonsurgically treated patients with drug-resistant temporal lobe epilepsy (TLE) were re-evaluated according to a detailed clinical, neuropsychological, and psychosocial protocol with a mean follow-up interval of 58 months. Freedom from seizures was achieved in 64% of the surgical group; yet 23% of the nonsurgical patients became seizure-free as a result of modifications in drug therapy. Generally, socioeconomic development was poorer in nonsurgical than in surgical patients. Freedom from seizures, employment, and the absence of depression were significant determinants of better quality of life. As for neuropsychological outcome, verbal memory impairment was common after left-sided temporal resection; however, there was no evidence of a marked progression of cognitive impairment after the first postoperative year. In nonsurgical patients, too, cognitive capacities were surprisingly stable over time, although persisting seizures and good baseline performance predicted a poorer neuropsychological outcome.

Adult↗
PubMed2000

Corticosteroid receptor mRNA expression in the brains of patients with epilepsy.

The effects of corticosteroids in the brain are mediated through the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). We used a sensitive competitive RT-PCR assay to quantify the amounts of GR and MR mRNA in human brain tissue specimens from patients with focal epilepsies. GR and MR mRNAs were expressed at approximately the same levels in the temporal lobe, frontal lobe, and hippocampus as compared to tissues with high glucocorticoid/mineralocorticoid receptor expression (liver/kidney). GR and MR mRNA concentrations in the temporal lobe increased markedly during childhood and reached adult levels at puberty. GR and MR mRNA expression was significantly higher in the temporal lobe and frontal lobe cortex of women than in those of men. In women, MR and GR mRNA concentrations were markedly lower in hippocampal tissue than in frontal and temporal lobe cortex tissue. In conclusion, our data demonstrate sex- and site-dependent expression of corticosteroid receptor mRNA in the human brain.

Adolescent↗
PubMed2000

Differential treatment in acute upper cervical spine injuries: a critical review of a single-institution series.

BACKGROUND: A single-institution series of injuries of the upper cervical spine are analyzed retrospectively and the literature relevant to the topic is reviewed. METHODS: Seventy patients (34 female, 36 male, mean age 47 years) were admitted during a 5-year period for injuries of the upper cervical spine. Sixty-five were followed for a mean time of 18 months. Three isolated ligamentous instabilities, 6 isolated C1 fractures, 3 complex C2 fractures, 10 combined C1/C2, and 48 C2 fractures (17 hangman's, 31 odontoid) were diagnosed. Twenty-nine patients were treated conservatively and for 41 patients surgery was the primary treatment. Twenty-three ventral odontoid screw fixations, 8 ventral platings and 10 dorsal stabilizations were performed. Stability was evaluated using flexion-extension radiography. Pain levels and neurological outcome were assessed. RESULTS: Operative mortality and neurological morbidity were 0%. Two wound infections and 3 instabilities (17%) in odontoid Type II fractures primarily treated with ventral odontoid screw fixation needed dorsal restabilization. During follow-up examinations the neurological status of three patients was improved. In 62 patients preoperative status was attained. Six patients evaluated their pain as severe, two as disabling. CONCLUSIONS: Candidates for surgery as the primary treatment include those with isolated ligamentous instabilities, Type III hangman's fractures and Type II odontoid fractures with dislocation more than 5 mm. In combined C1/C2 fractures the axis fracture dictates the treatment strategy. Patients who undergo dorsal procedures and have involvement of C1 have a greater chance of developing persistent pain.

Acute Disease↗
PubMed2000

Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1, 2, 3 and 4 in epileptic human hippocampus.

Sex steroid hormones exert important influences on neuroendocrine and behavioural brain function. As neuroactive steroids they are able to modify neuronal excitability. Unbalanced synthesis may thus be implicated in pathophysiological conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial role in catalyzing the final steps of androgen and estrogen biosynthesis. The hippocampus appears to be a major target area of neurosteroidal action. The expression of 17beta-HSD isozymes has not yet been studied in human hippocampus. Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in hippocampal tissue specimens obtained at neurosurgery from 42 patients with pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000 fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3 mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4 concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus showed no significant differences between men and women and there were no significant differences in expression levels of these enzymes between patients with Ammon's horn sclerosis (AHS) and those with histopathologically normal hippocampus associated with extrahippocampal lesions. No significant correlation could be detected between duration of epilepsy, individual seizure frequency and expression levels of 17beta-HSDs. In conclusion, the present study is the first to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the human hippocampus also, our data provide further evidence for the existence of sex steroid formation and metabolism in this specific brain area.

17-Hydroxysteroid Dehydrogenases↗
PubMed2000

Differential mRNA expression of the two mineralocorticoid receptor splice variants within the human brain: structure analysis of their different DNA binding domains.

In human brain tissue, cortisol action, at basal concentrations, is mediated by the mineralocorticoid receptor (MR). An in-frame insertion of 12 bp in the MR-DNA-binding domain due to alternative splice site usage between exons 3 and 4 results in an MR mRNA splice variant (MR+4) encoding a receptor protein with four additional amino acids compared to the wild-type MR protein. To elucidate the questions of sex, age, and/or tissue dependent differences of the relative amount of the two mRNA subtypes, we examined 131 fresh human brain tissue samples from temporal and frontal lobe or hippocampus. One hundred and twenty samples were obtained from patients with epilepsy and 11 samples from patients with brain tumours. A small but significant difference of the MR+4 mRNA splice variant proportions in cortex (9.5 +/- 0.8%) and subcortical white matter (6.6 +/- 0.7%) of the temporal lobe could be detected, indicating differential MR splice variant expression within these brain areas. Moreover, the splice variant ratios in samples of the temporal lobe cortex collected from patients with epilepsy differed from samples of patients with brain tumours. These data point to an altered expression of the MR splice variants in epilepsy, and strengthen the supposition of a tissue specific alternative splicing of the MR mRNA. The frequent occurrence of the MR+4 transcript raises the question of its functional significance. For this reason, an MR+4 DNA-binding-domain structure model was generated by computer-based homology modelling based on the known glucocorticoid receptor structure. The data obtained revealed no distorting effect of the inserted four amino acids on the adjacent secondary structures, thereby suggesting that both zinc fingers retain their function. The resulting structure of the MR+4 model leads to the supposition that the receptor retains its function. Moreover, databank analysis with respect to this kind of steroid receptor variation and our own sequence data of the closely related progesterone receptor sustained the hypothesis that only corticosteroid receptors were affected by this alternative splicing event.

Adult↗
PubMed2000

Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances.

Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal lobe epilepsy (TLE). In patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE. During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.

Adult↗
PubMed2000

Capillary oxygen saturation and tissue oxygen pressure in the rat cortex at different stages of hypoxic hypoxia.

The objective of this study was to generate data that allow for estimation of the validity of oxygen saturation (SO2) values in superficial cortical capillaries as calculated by a microreflectometric system (EMPHO II). Capillary SO2 and tissue oxygen pressure (PtO2) were measured simultaneously in the cortex of n = 13 Wistar rats under normocapnic (PaCO2 = 36 mmHg) arterial normoxia (PaO2 = 92 mmHg), moderate (paO2 = 53 mmHg) and severe hypoxic hypoxia (PaO2 = 31 mmHg) with microreflectometry and multiwire surface electrodes. Values were pooled according to arterial oxygenation levels, displayed as frequency histograms and compared via ANOVA (p < 0.05). In a Hill-plot (log PtO2 versus log SO2/(100 - SO2)) an in vivo tissue oxygen dissociation curve was obtained and a linear regression/correlation analysis performed. Mean +/- SD values of SO2 respectively PtO2 decreased from 45.6% +/- 14.6% resp. 26.8 +/- 8.2 mmHg during arterial normoxia to 32.6% +/- 10.2% resp. 20.2 +/- 6.6 mmHg during moderate and to 12.3% +/- 11.1% resp. 8.7 +/- 5.0 mmHg during severe hypoxic hypoxia. Linear regression analysis in the Hill-plot of values between 1% and 65% SO2 and 0.1 and 41 mmHg PtO2 revealed an excellent correlation (r2 = 0.88) with an increase of scatter below 10% SO2 or 1.5 mmHg PtO2. We conclude that SO2 values calculated by the algorithm of the applied microreflectometric system reflect very accurately cortical oxygen supply over a very wide range of oxygenation levels when compared to a gold standard reference. Only at extremely low levels (e.g. below 10% SO2) did we find possible inaccuracies with regard to truly absolute saturation values.

Animals↗