On the role of NO in the thalamus.
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Animals↗
Biomedical subjects
H C Pape
Publications and source records attributed to H C Pape.
Modulatory effects of adenosine on inhibitory postsynaptic potentials in the lateral amygdala of the rat.
1. Adenosine is a depressant in the central nervous system with pre- and postsynaptic effects. In the present study, intracellular recording techniques were applied to investigate the modulatory effects of adenosine on projection neurons in the lateral rat amygdala (LA), maintained as slices in vitro. 2. Adenosine reversibly reduced the amplitude of a fast inhibitory postsynaptic potential (IPSP) that was evoked by electrical stimulation of the external capsule and pharmacologically isolated by applying an N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor antagonist, DL-(-)-2-amino-5-methyl-4-isoxazolepropionic acid and 6, 7-Dinitroquinoxaline-2,3-dione, respectively, and the gamma-aminobutyric acidB (GABAB) receptor antagonist CGP 35348. The postsynaptic potential that remained was abolished by locally applying bicuculline. 3. Adenosine reduced the amplitude of the fast IPSP on average by 40.3%. It had no significant effect on responses to exogenously applied GABA, on membrane potential or on input resistance, suggesting that the site of action was at presynaptic inhibitory interneurons in the LA. 4. The response to adenosine was mimicked by the selective adenosine A1 receptor agonist N6-cyclohexyladenosine and blocked by the selective adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine. 5. Neuronal responsiveness in the amygdala is largely controlled by inhibitory processes. Adenosine can presynaptically downregulate inhibitory postsynaptic responses and could exert dampening effects likely by depression of both excitatory and inhibitory neurotransmitter release.
Adenosine↗
Long term results after multiple injuries including severe head injury.
OBJECTIVE: To describe the long term results in patients with multiple injuries including severe head injury. DESIGN: Retrospective and prospective clinical study. SETTING: Level I trauma centre, Germany. PATIENTS: Patients aged 16-60 years who had been injured more than 2 years before, whose Injury Severity Score was over 20 and whose cranial Abbreviated Injury Score (AIS) was over 3. MAIN OUTCOME MEASURES: Glasgow Outcome Scale (GOS), functional, neuropsychological, vocational and social outcomes. RESULTS: 58 patients, median age 24 (range 16-53, interquartile range (IQR) 21-32) years were investigated 5 (3-9; IQR 4-7) years after their injury. Median ISS was 34 (21-57; IQR 26-41) and GCS 6 (3-8; IQR 4-7). Duration of coma was 10 (2-51; IQR 7-22) days and neurological rehabilitation lasted 169 (10-830; IQR 80-300) days. Movements of the elbow and ankle was most impaired by injury. All psychometric tests showed deficits, particularly in speed of processing, concentration, recent memory, and learning performance. The social environment had been changed in half and vocational rehabilitation was dependent on age. 24 (42%) returned to their former profession, 18 (31%) were retrained to another profession, 16 (27%) were unemployed or retired on a pension. 31 (53%) made a good recovery with moderate disability, 19 (33%) had severe disability, and 8 (14%) remained in a persistent vegetative state assessed by the GOS. CONCLUSION: Early and concentrated rehabilitation facilitates functional, social, and neuropsychological reintegration.
Adolescent↗
Cellular reactivity to mechanical axonal injury in an organotypic in vitro model of neurotrauma.
An in vitro model of traumatic brain injury is described that is based on organotypic cocultures (OTCs) of rat neocortex and thalamus connected by reciprocal axonal projections. Localized mechanical compression of this projection was inflicted with a mechanical device, and the effects on cell viability, axonal morphology, and protein expression levels were analyzed. Within 24 h after insult, major cell damage occurred in infragranular cortical layers containing the corticothalamic projection neurons and in thalamic regions adjacent to the mechanical impact as was assessed through the use of the vital stain Syto 21, and propidium iodide labeling. A small, but significant number of calretinin-positive interneurons in cortical and thalamic areas displayed symptoms of injury. Axonal elements, as revealed by neurofilament (NF-H/M) immunohistochemistry, in the corticothalamic transition zone displayed pathomorphological changes, such as axonal bulbs and swellings, already 4 h after insult. Densitometric analysis revealed that MAP-2a,b expression was not significantly changed within 4 h after injury. A significant reduction in MAP-2a,b amount was evident at 20 h after injury in thalamus (by 31.6%) and cortex (by 30%) maintained for 12 days in vitro (DIV), but not in OTCs aged 20 DIV. The axonally localized form MAP-2c significantly increased in cortex of 12-DIV OTCs at 4 and 20 h after insult (65.6% and 33.4%, respectively). MAP-2c levels in cortex of 20 DIV initially increased by 47.7% and declined below control values 20 h after injury. Thalamic areas revealed a delay in MAP-2c reactivity, in that expression was significantly elevated only at 20 h after injury (by 84.4% in 12-DIV and by 39.6% in 20-DIV OTCs, respectively). These data may reflect the regenerative ability of juvenile, but not of older neurons in response to mechanical axonal injury.
Animals↗
Long-term outcome in children with fractures of the proximal femur after high-energy trauma.
BACKGROUND: Fractures of the femoral head and neck in children have a risk of severe complications, especially femoral head necrosis. We performed a long-term follow-up study of patients treated at our institution. METHODS: Patients were reexamined at least 3 years after trauma and were included if they were younger than 17 years old at the time of injury, if there was no history of previous fracture, and if there was no history of underlying bone disease. Fractures were classified according to Delbet, and outcome was graded according to Ratliff. Anterior capsulotomy was not performed, and stabilization devices were placed short of the epiphysis except for type I fractures. RESULTS: Of 32 patients, 28 were reexamined. Among these patients, the mean age at the time of injury was 11.8 years and the mean follow-up time was 11.1 years (range, 3-21 years). There were 3 patients with type I fractures, 8 patients with type II fractures, 12 patients with type III fractures, and 5 patients with type IV fractures. Thirteen patients had Injury Severity Scores > 18. At last follow-up, 20 patients presented with good function, 5 with fair outcome, and 3 with poor results; all of the latter suffered type I fractures. Eighteen patients had no restrictions in activities of daily living or during sports activities. In six other patients, the inability to participate in sports was attributable to head trauma, amputation, or peripheral neurologic damage. CONCLUSION: We found favorable long-term outcome in type II to type IV fractures. In these patients, restrictions of function were usually caused by other associated injuries. All patients with type I fractures presented with poor outcome secondary to their proximal femoral fractures, and not because of other associated injuries. Type I fractures during childhood and adolescence represent an unsolved problem.
Accidents↗
Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure?
BACKGROUND: We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. METHODS: Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. RESULTS: The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). CONCLUSION: In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.
Adult↗
Pulmonary and systemic fat embolization after medullary canal pressurization: a hemodynamic and histologic investigation in the dog.
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Animals↗
The use of Poller screws as blocking screws in stabilising tibial fractures treated with small diameter intramedullary nails.
Intramedullary nailing of metaphyseal fractures may be associated with deformity as a result of instability after fixation. Our aim was to evaluate the clinical use of Poller screws (blocking screws) as a supplement to stability after fixation with statically locked intramedullary nails of small diameter. We studied, prospectively, 21 tibial fractures, 10 in the proximal third and 11 in the distal third in 20 patients after the insertion of Poller screws over a mean period of 18.5 months (12 to 29). All fractures had united. Healing was evident radiologically at a mean of 5.4+/-2.1 months (3 to 12) with a mean varus-valgus alignment of -1.0 degree (-5 to 3) and mean antecurvatum-recurvatum alignment of 1.6 degrees (-6 to 11). The mean loss of reduction between placement of the initial Poller screw and follow-up was 0.5 degrees in the frontal plane and 0.4 degrees in the sagittal plane. There were no complications related to the Poller screw. The clinical outcome, according to the Karström-Olerud score, was not influenced by previous or concomitant injuries in 18 patients and was judged as excellent in three (17%), good in seven (39%), satisfactory in six (33%), fair in one (6%), and poor in one (6%).
Adolescent↗
Intrinsic properties of reticular thalamic neurons relevant to genetically determined spike-wave generation.
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Action Potentials↗
Postsynaptic mechanisms underlying responsiveness of amygdaloid neurons to nociceptin/orphanin FQ.
Effects of nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid-like orphan receptor (ORL), were investigated in the rat lateral (AL) and central (ACe) amygdala in vitro. Approximately 98% of presumed projection neurons in the AL responded to N/OFQ with an increase in inwardly rectifying potassium conductance, resulting in an impairment in cell excitability. Half-maximal effects were obtained at 30.6 nM; the Hill coefficient was 0.63. In the ACe, 31% of the cells displayed responses similar to that in the AL, 44% were nonresponsive, and 25% responded with a small potassium current with a linear current-voltage relationship. Responses to N/OFQ were reduced by 100 microM Ba2+, were insensitive to 10 microM naloxone, and were blocked by a selective ORL antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 (IC50 = 760 nM). Involvement of G-proteins was indicated by irreversible effects and blockade of action of N/OFQ during intracellular presence of GTP-gamma-S (100 microM) and GDP-beta-S (2 mM), respectively, and prevention of responses after incubation in pertussis toxin (500 ng/ml). These mechanisms may contribute to the role of N/OFQ in the reduction of fear responsiveness and stress that have recently been suggested on the basis of histochemical and behavioral studies.
Action Potentials↗
Postnatal expression pattern of calcium-binding proteins in organotypic thalamic cultures and in the dorsal thalamus in vivo.
The present study describes the postnatal expression of calbindin, calretinin and parvalbumin and glutamic acid decarboxylase (GAD) and microtubule-associated protein 2 (MAP2) in organotypic monocultures of rat dorsal thalamus compared to the thalamus in vivo. Cultures were maintained for up to 7 weeks. Cortex-conditioned medium improved the survival of thalamic cultures. MAP2-immunoreactive material was present in somata and dendrites of small and large-sized neurons throughout the cultures. Parvalbumin immunoreactivity was present in larger multipolar or bitufted neurons along the edge of a culture. These neurons also displayed strong parvalbumin mRNA and GAD mRNA expression, and GABA immunoreactivity. They likely corresponded to cells of the nucleus reticularis thalami. Parvalbumin mRNA, but neither parvalbumin protein nor GAD mRNA, was expressed in neurons with large somata within the explant. They likely represented relay cells. GAD mRNA, but not parvalbumin mRNA, was expressed in small neurons within the explants. Small neurons also displayed calbindin- and calretinin-immunoreactivity. The small neurons likely represented local circuit neurons. The time course of expression of the calcium-binding proteins revealed that all were present at birth with the predicted molecular weights. A low, but constant parvalbumin expression was observed in vitro without the developmental increase seen in vivo, which most likely represented parvalbumin from afferent sources. In contrast, the explantation transiently downregulated the calretinin and calbindin expression, but the neurons recovered the expression after 14 and 21 days, respectively. In conclusion, thalamic monocultures older than three weeks represent a stable neuronal network containing well differentiated neurons of the nucleus reticularis thalami, relay cells and local circuit neurons.
Aging↗
[Pediatric polytrauma. A retrospective comparison between pediatric, adolescent and adult polytrauma].
Numerous epidemiological studies about multiple trauma patients do not include an analysis of patients under the age of 18. To study this, the data of 682 patients with multiple traumata, treated between 1981 and 1991 at Hannover Medical School, Germany, were retrospectively analyzed. The patients were divided into four age-related groups: preschool age (< 6 years), school age (< 13 years), teenagers (< 18 years) and adults (> or = 18 years). Analyzed were the cause of trauma, localization of injuries and the cause of death. Children were less often injured as passengers in cars, but more often injured as pedestrians and bicyclists than adults. However, children showed a significant higher mortality than adults, with threefold increased risk of death when they injured as passengers in car accidents. In all groups injuries to the head and the legs were most common. Children showed a lower incidence of trauma to the thorax, abdomen, hip and arms than the adult group. Nevertheless, trauma to the thorax, abdomen and head was associated with the highest risk of death in all groups. Spinal cord injuries, especially injuries to the neck, also showed a high risk of death. Children younger than 6 years had the most severe head injuries. Safety improvements for children in cars, helmet usage on bicycles and early training in traffic safety for children might decrease the lethality in this group of trauma patients.
Adolescent↗
Multiple organ failure (MOF) after severe trauma--a sheep model.
OBJECTIVE: To perform a reproducible long-term (10 days) large animal model of multiple systems organ failure without necessity of a continuous stimulus. DESIGN: Adult female merino sheep submitted to a 5-day stimulation period followed by a 5-day observation period. Day 1: Hemorrhagic shock was combined with a traumatic surgical insult (reamed intramedullary femoral nailing), followed by serial administrations every 12 h for 5 days of a combination of endotoxin and zymosan activated plasma. Organ function was followed for 5 further days. RESULTS: Cardiac index increased significantly during the study (day 1: 491 +/- 8 mm Hg; day 10: 427 +/- 20, p < 0.05). Liver function was impaired and bilirubin levels increased significantly (day 1: 2.9 +/- 0.3 micromol/l; day 10: 7.2 +/- 0.9; p < 0.05). Creatinine clearance decreased initially (day 1: 54 +/- 7 ml/min), increased to a peak on day 2 (104 +/- 27), and then deteriorated again (day 10: 53 +/- 18). CONCLUSION: This new large animal model of trauma-induced MOF is reproducible and may be suitable for the study of new therapeutic approaches to therapy.
Albumins↗
Is early kinetic positioning beneficial for pulmonary function in multiple trauma patients?
Body positioning (kinetic therapy) is known to improve oxygenation in patients with impaired pulmonary function and ARDS. We have used body positioning prophylactically in trauma patients whose injury and pattern predispose to ARDS. This retrospective study reports the effects of early prophylactic (group P) versus late (group L) axial rotation on pulmonary function and the incidence of ARDS. Both groups were comparable in age, injury severity and the degree of thoracic injury. Systemic oxygenation was significantly better and the incidence of ARDS significantly lower in group P (group P: 34.3 per cent, group T: 74.1 per cent, P < 0.05). There was a tendency towards a lower incidence of pneumonia and a better survival in group P, which did not reach statistical significance. The duration of kinetic therapy and of ventilation was comparable in both groups. In this retrospective evaluation early prophylactic kinetic therapy was associated with a significantly lower incidence of ARDS compared with that instigated later.
Adult↗
Strychnine-sensitive glycine responses in neurons of the lateral amygdala: an electrophysiological and immunocytochemical characterization.
Electrophysiological and staining techniques in the in vitro slice preparation of the rat and guinea-pig lateral amygdala were combined with immunocytochemical approaches, in order to characterize the neuronal substrate, the ionic basis and the pharmacological properties of glycine-mediated responses, and to map the distribution and composition of the mediating glycine receptors. Glycine was locally applied to spiny, pyramidal-like cells in the lateral amygdala, which possessed electrophysiological properties typical of projection neurons. Glycine induced a membrane hyperpolarization from rest and associated decrease in input resistance, and an interruption of spike firing and calcium-mediated high-threshold oscillations. The glycine-mediated response persisted during blocked synaptic transmission, reversed close to the presumed somatic chloride equilibrium potential and shifted during altered transmembrane Cl- gradients as expected for an increase in membrane chloride conductance. Responses to glycine were reversibly blocked by strychnine, but were insensitive to picrotoxin and bicuculline. Strychnine-sensitive components of spontaneous activity, but not of evoked synaptic responses, were frequently observed. Similar responses to glycine occurred in neurons of the guinea-pig and rat lateral amygdala, as well as in the central amygdala. The localization and composition of glycine receptors were examined through the use of monoclonal antisera directed against the binding protein (gephyrin), the alpha1 subunits (mAb2b) and alpha/beta subunits (mAb4a) of glycine receptors. A dense to moderate immunostaining for gephyrin was observed throughout the amygdaloid complex, whereas mAb4a immunofluorescent neurons, displaying strong punctate labelling around the soma and proximal dendrites, were confined to the lateral amygdala. No immunoreactivity was obtained with mAb2b antibodies in the amygdala. It is concluded that pyramidal-like projection cells in the lateral amygdala express functional glycine receptors at somatic and proximal dendritic sites, which are composed of beta and alpha subunits other than the alpha1 type, and which may play a functional role in the control of excitatory activity in the amygdala, particularly during periods of decreased GABAergic influence.
Amygdala↗
Distribution of L-type calcium channels in rat thalamic neurones.
One major pathway for calcium entry into neurones is through voltage-activated calcium channels. The distribution of calcium channels over the membrane surface is important for their contribution to neuronal function. Electrophysiological recordings from thalamic cells in situ and after acute isolation demonstrated the presence of high-voltage activated calcium currents. The use of specific L-type calcium channel agonists and antagonists of the dihydropyridine type revealed an about 40% contribution of L-type channels to the total high-voltage-activated calcium current. In order to localize L-type calcium channels in thalamic neurones, fluorescent dihydropyridines were used. They were combined with the fluorescent dye RH414, which allowed the use of a ratio technique and thereby the determination of channel density. The distribution of L-type channels was analysed in the three main thalamic cell types: thalamocortical relay cells, local interneurones and reticular thalamic neurones. While channel density was highest in the soma and decreased significantly in the dendritic region, channels appeared to be clustered differentially in the three types of cells. In thalamocortical cells, L-type channels were clustered in high density around the base of dendrites, while they were more evenly distributed on the soma of interneurones. Reticular thalamic neurones exhibited high density of L-type channels in more central somatic regions. The differential localization of L-type calcium channels found in this study implies their predominate involvement in the regulation of somatic and proximal dendritic calcium-dependent processes, which may be of importance for specific thalamic functions, such as those mediating the transition from rhythmic burst activity during sleep to single spike activity during wakefulness or regulating the relay of visual information.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Mechanisms and functional significance of a slow inhibitory potential in neurons of the lateral amygdala.
A slow inhibitory potential (sIP) elicited upon synaptic activation in spiny, pyramidal-like cells with properties indicative of projection neurons was investigated in slices of the rat and guinea-pig lateral amygdala in vitro. The sIP succeeded the triphasic sequence of excitatory and fast/slow inhibitory postsynaptic potentials mediated via glutamate and GABA(A/B) receptors, respectively, was readily evoked upon repetitive stimulation of the external capsule and appeared to terminate epileptiform burst discharges during pharmacologically reduced GABAergic influence. The sIP reversed close to the Cl- equilibrium potential, but was not affected by altered transmembrane Cl- gradients and not abolished by antagonists to ligand-gated Cl- channels. Intracellular injection of QX 314 and resulting blockade of sodium spikes had no effect, whereas the Ca2+ chelator BAPTA blocked the sIP concomitantly with slow hyperpolarizing afterpotentials following intrinsically generated spike firing, thereby indicating the contribution of Ca2+-dependent mechanisms secondary to synaptic activation. During action of BAPTA and QX 314, an N-methyl-D-aspartate (NMDA) receptor-mediated potential was unmasked, which contributed to the sIP. The Ca2+-dependent mechanisms of the sIP involved a membrane K+ conductance, as was indicated by the dependence on the K+ gradient and the shift of the reversal potential towards the K+ equilibrium potential during blocked NMDA receptors. During the presence of GABA receptor antagonists, reduction of the Ca2+-activated K+ conductance through injection of BAPTA or application of dopamine induced a gradual shift of interictal-like single bursts of spikes towards the generation of re-occurring ictal-like activity. It is concluded that pyramidal-like projection cells in the AL can generate a sIP upon synaptic activation, which reflects the combined activation of an NMDA receptor-mediated cation current and a K+ current that is secondary to the rise in intracellular Ca2+ concentration resulting from the preceding depolarizing response. The sIP may play an important role in controlling excitatory activity in the amygdala, particularly in preventing the transformation of interictal-like activity towards recurrent epileptic discharges during periods of decreased GABAergic influence.
Amygdala↗
Relations between cortical and thalamic cellular activities during absence seizures in rats.
In a rat model of generalized absence epilepsies (Genetic Absence Epilepsy Rats from Strasbourg, GAERS), multiunit activity was recorded simultaneously at different sites of the thalamocortical system under neurolept anaesthesia (fentanyl-droperidol). Under these conditions, bilaterally synchronized spike-and-wave-discharges (SWDs) occurred spontaneously on the electroencephalogram (EEG) that were in principle identical to those reported earlier from unanaesthetized preparations. The generation of SWDs on the EEG was associated with spike-concurrent, rhythmic burst-like activity in (mono-)synaptically connected regions of specific (somatosensory) thalamic regions and layers IVN of the somatosensory cortex, and the reticular thalamic nucleus. Precursor activity was typically recorded in cortical units, concomitant with 'embryonic' SW seizures on the EEG, before the paroxysm was evident on the gross EEG and in the thalamus. On average, SWD-correlated activity in layers IVN of the somatosensory cortex started significantly earlier than correlated burst-like firing in reticular and in ventrobasal thalamic neurons. Cellular peak firing in thalamus and cortex during bilaterally synchronized SWDs was related to the spike component on the gross EEG with the temporal rank order ventroposteromedial > ventrolateral > or = ventroposterolateral thalamic > > rostral reticular thalamic nuclei > or = cortex (layers IVN) = caudal reticular thalamic nucleus. A spike-related depression and wave-related increase in firing was recorded in anteroventral ventrolateral thalamic areas, presumably reflecting their peculiar anatomical arrangement within the thalamus. These results from an in vivo preparation with intact synaptic connections that spontaneously produces SWDs indicate that SWDs spread within the thalamocortical network, involving short and long delays. The order of concurrent rhythmic firing observed in thalamocortical circuits during SW seizures are supportive of the hypothesis that the processes of rhythmogenesis recruit local thalamic networks, while cortical mechanisms appear to synchronize rhythmic activities on a larger spatiotemporal scale, thereby providing an important contribution to the generalization of epileptiform activity and expression of SWDs on the EEG.
Animals↗