Nonlinear two-level dynamics of quantum time crystals.

A time crystal is a macroscopic quantum system in periodic motion in its ground state. In our experiments, two coupled time crystals consisting of spin-wave quasiparticles (magnons) form a macroscopic two-level system. The two levels evolve in time as determined intrinsically by a nonlinear feedback, allowing us to construct spontaneous two-level dynamics. In the course of a level crossing, magnons move from the ground level to the excited level driven by the Landau-Zener effect, combined with Rabi population oscillations. We demonstrate that magnon time crystals allow access to every aspect and detail of quantum-coherent interactions in a single run of the experiment. Our work opens an outlook for the detection of surface-bound Majorana fermions in the underlying superfluid system, and invites technological exploitation of coherent magnon phenomena - potentially even at room temperature.

Intraoperative pressure measurement in radial artery harvest. A tool with additional value?

OBJECTIVES: The radial artery is widely used as a graft in coronary artery bypass surgery (CABG). Due to its location and function it should be screened prior to harvesting to avoid ischaemic complications of the hand. In acute situations the Allen test is often the only preoperative screening method available. As has been noted earlier, a negative Allen test does not mean a non-harvestable radial artery. We endeavoured to find out whether intraoperative pressure measurement could be used as a complement while screening the radial artery. DESIGN: Ninety patients planned for elective CABG with radial artery as a conduit were examined preoperatively with the Allen test, handheld Doppler and pletysmography of the second and fourth digits. Radial artery pressure was measured intraoperatively. Symptom scale was recorded pre- and postoperatively. RESULTS: There were ten patients with a positive Allen test. The intraoperative index of radial artery pressures was 0.868 in the Allen positive group and 0.885 in the Allen negative group with no statistically significant difference (P value .68). Tolerance of exercise and cold was significantly impaired postoperatively, P values .002 and .001 respectively. No ischaemic complications occurred. CONCLUSIONS: Intraoperative pressure measurement can be used when screening radial arteries are to be harvested and no metric preoperative screening methods are available.

Pulmonary function and immediate and late outcome after coronary artery bypass surgery.

AIM: The aim of this study was to evaluate whether pulmonary function as assessed by spirometry affects the immediate and late outcome after isolated coronary artery bypass surgery (CABG). METHODS: Data on preoperative percentages of the predicted forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were retrieved from a series of 1848 patients who underwent isolated CABG. Pulmonary disease was defined according to EuroSCORE criteria. RESULTS: Logistic regression showed that percentage of predicted FVC was an independent predictor of in-hospital mortality along with estimated glomerular filtration rate, age and extracardiac arteriopathy. Cox regression analysis showed that pulmonary disease and percentages of predicted FVC were independent predictors of late overall mortality. Percentage of predicted FVC < 70% (at 10-year: 63.8% vs. 74.3%, Cox regression analysis: P = 0.014, RR 1.50, 95%C.I. 1.08-2.08) and pulmonary disease (at 10-year: 58.0% vs. 76%, Cox regression analysis: P < 0.0001, RR 1.75, 95%C.I. 1.29-2.39), but not percentage of predicted FEV1 < 70%, were associated with a marked decrease in late survival. CONCLUSION: This study confirmed the significant, negative prognostic impact of pulmonary disease on the immediate and long-term survival after isolated CABG.

Half-quantum vortices and walls bounded by strings in the polar-distorted phases of topological superfluid 3He.

Symmetries of the physical world have guided formulation of fundamental laws, including relativistic quantum field theory and understanding of possible states of matter. Topological defects (TDs) often control the universal behavior of macroscopic quantum systems, while topology and broken symmetries determine allowed TDs. Taking advantage of the symmetry-breaking patterns in the phase diagram of nanoconfined superfluid 3He, we show that half-quantum vortices (HQVs)-linear topological defects carrying half quantum of circulation-survive transitions from the polar phase to other superfluid phases with polar distortion. In the polar-distorted A phase, HQV cores in 2D systems should harbor non-Abelian Majorana modes. In the polar-distorted B phase, HQVs form composite defects-walls bounded by strings hypothesized decades ago in cosmology. Our experiments establish the superfluid phases of 3He in nanostructured confinement as a promising topological media for further investigations ranging from topological quantum computing to cosmology and grand unification scenarios.

Epileptogenesis after cortical photothrombotic brain lesion in rats.

We investigated epileptogenesis after cortical photothrombotic stroke induced with Rose Bengal dye in adult Sprague-Dawley rats. To detect spontaneous seizures, video-electroencephalograms were recorded at 2, 4, 6, 8, and 10 months for 7-14 days (24 h/day). At the end, spatial and emotional learning and memory were assessed using the Morris water-maze and fear-conditioning test, respectively, and the brains were processed for histologic analysis. Seizures were detected in 18% of rats that received photothrombosis. The average seizure frequency was 0.39 seizures per recording day and mean seizure duration was 117 s. Over 60% of seizures occurred during the dark hours. Rats with photothrombotic lesions were impaired in the water-maze (P<0.05) but not in the fear-conditioning test as compared with controls. Histology revealed that lesion depth varied from cortical layers I to VI in photothrombotic rats with epilepsy. Epileptic rats had light mossy fiber sprouting in the inner molecular layer of the dentate gyrus both ipsilateral and contralateral to the lesion. This study extends the current understanding of epileptogenesis and functional impairment after cortical lesions induced by photothrombosis. Our observations support the hypothesis that photothrombotic stroke in rats is a useful animal model for investigating the mechanisms of post-stroke epileptogenesis.

A model of posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats.

Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3+/-0.2 seizures per day and mean seizure duration was 113+/-46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66+/-37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies.

Chronic elevation of brain GABA levels beginning two days after status epilepticus does not prevent epileptogenesis in rats.

Vigabatrin (VGB) treatment is neuroprotective in various models of status epilepticus (SE) and delays the development of kindling via mechanisms that are assumed to relate to the elevation of GABA levels in the brain. Here, we tested the hypothesis that a chronic elevation of brain GABA levels obtained by VGB treatment prevents the development of spontaneous seizures (i.e. epilepsy) following SE in rats. Self-sustained SE (SSSE) was induced by stimulating the lateral nucleus of the amygdala. Two days later, chronic VGB (75 mg/kg/day) or saline treatment was started via subcutaneous osmotic minipumps. The development of spontaneous seizures was monitored once a week (24 h at a time) using video-EEG recording. Rats were perfused for histology either at the end of the 10-week drug treatment, or later at the end of an 8-week drug-free follow-up period. Before perfusion for histology, spatial learning and memory perform was tested in the Morris water-maze. Spontaneous seizures were observed in 55% (6/11) of the saline-treated and 73% (8/11) of the VGB-treated rats during the 10-week treatment period. Seizure frequency, severity, and duration were similar in VGB-treated rats and controls during and after the drug-treatment period. VGB treatment did not decrease neuronal damage in various temporal lobe regions or mossy fiber sprouting. VGB treatment also did not attenuate spatial learning or memory impairments. These findings indicate that the augmentation of GABAergic neurotransmission by VGB does not prevent the development of epilepsy when treatment is started 2 days after SE.

Administration of caspase 3 inhibitor during and after status epilepticus in rat: effect on neuronal damage and epileptogenesis.

Symptomatic temporal lobe epilepsy typically develops in three phases: brain damage --> epileptogenesis --> spontaneous seizures (epilepsy). The challenge is to prevent epileptogenesis after injury. We hypothesized that alleviation of damage by caspase inhibitors will reduce epileptogenesis or at least have disease-modifying effects (less severe epilepsy, milder cognitive decline). Epileptogenesis was triggered by amygdala stimulation-induced status epilepticus (SE) in rats and spontaneous seizures were monitored with video-electroencephalography (EEG). First, we tested the neuroprotective effect of a 1-week treatment with caspase 1, 3 or 9 inhibitors (3 micro g/d/i.c.v., started 3 h after the beginning of SE). The least damage to the hippocampus was observed in animals treated with the caspase 3 inhibitor (z-DEVD-fmk) which reduced the enzyme activity to 6% of that in the vehicle group. Thus, z-DEVD-fmk was chosen for long-term studies, in which the treatment regime remained the same except the dose was doubled (6 micro g/d/i.c.v.). Video-EEG monitoring was performed for 3 to 4 weeks, starting either 8 or 14 weeks after SE. One group of animals was tested in water-maze and fear-conditioning tests, and all animals were perfused for histological analysis. Treatment with the caspase 3 inhibitor neither prevented the development of epilepsy, nor had any disease-modifying effects. Mossy fibre sprouting, however, was reduced. The present data indicate that administration of z-DEVD-fmk monotherapy was not antiepileptogenic despite its short-term neuroprotective effects. These findings challenge the idea that prevention of cell death is the primary target for the development of antiepileptogenic compounds.

Electrophysiologic changes in the lateral and basal amygdaloid nuclei in temporal lobe epilepsy: an in vitro study in epileptic rats.

The functional consequences of neuronal loss during epileptogenesis in the lateral and basal amygdaloid nuclei are poorly understood. The present study tested the hypothesis that electrical responsiveness varies in different amygdaloid nuclei in the chronically epileptic amygdala. Further, we examined the amygdaloid region most prone to seizure initiation. Epileptogenesis was triggered in 20 rats by inducing status epilepticus (SE) with electrical stimulation of the lateral nucleus of the amygdala. Electrode-implanted non-stimulated rats served as controls. The occurrence and duration of spontaneous seizures were monitored with video-electroencephalography (EEG) at 8-9 weeks after SE. Thereafter, animals were killed and extracellular recordings were made from slices of both amygdalas. In the lateral nucleus of epileptic animals, the frequency of spontaneous responses was reduced compared with controls (P < 0.05). The amplitudes of evoked field responses were reduced (P < 0.01), whereas paired pulse (PP) facilitation was enhanced (P < or = 0.05). In the basal nucleus of the epileptic animals, PP facilitation was enhanced (P < 0.05) and sensitivity to 4-aminopyridine (4-AP)-induced epileptiform activity was increased compared with controls (P < 0.05). In the epileptic animals, the basal nucleus was also more sensitive than the lateral nucleus to 4-AP-induced epileptiform activity (P < 0.05). Correlation analysis indicated that longer SE duration was associated with longer half widths (P = 0.001) and smaller slopes (P < 0.05) of evoked responses as well as with attenuated PP facilitation (P<0.01). Moreover, a higher frequency of spontaneous seizures was associated with longer half widths (P < 0.05) and smaller slopes (P < 0.05) of evoked responses as well as with enhanced PP facilitation (P < 0.05). These data suggest that there is a reduced release of glutamate and reduced inhibition in the lateral and basal amygdaloid nuclei in epileptic animals. Further, the basal nucleus is more prone to epileptic activity than the lateral nucleus. Finally, the severity of SE and spontaneous seizures in vivo is associated with electrophysiologic alterations in vitro.

Ultrastructural changes during continuous retrograde warm and mild hypothermic blood cardioplegia for coronary bypass operations.

Ultrastructural changes in myocardial tissue were studied in 21 patients undergoing elective aorta-coronary bypass operation. The patients were randomized into two groups, with 10 of them receiving continuous retrograde warm and 11 continuous retrograde mild hypothermic blood cardioplegia. Biopsy specimens for electron microscopy were taken from the apical part of the left ventricle before and at the end of the aortic crossclamp period and after reperfusion of the myocardium. The ultrastructural changes were analyzed with use of a semiquantitative scoring system and classified as mild, moderate, or severe. Slight ultrastructural changes were found in both groups even before the aortic crossclamp period. At the end of the aortic crossclamp period the most prominent ultrastructural changes were mitochondrial swelling, damage of capillary endothelium, and clearing of the nucleoplasm or margination of chromatin, but some enlargement in intercalated discs was also discernible. Reperfusion of the myocardium for 15 minutes somewhat further increased the overall score of the ultrastructural changes. Two patients in the warm cardioplegia group had a perioperative myocardial infarction, and this may be one reason for the higher postoperative creatine kinase MB efflux in this patient group. Despite this finding, no major differences in the ultrastructural changes between the two cardioplegia groups could be observed. We conclude that only mild to moderate and principally reversible ultrastructural changes occur in myocardium during continuous retrograde warm and mild hypothermic blood cardioplegia for coronary bypass operation.

Seizure-induced damage to the hippocampus is prevented by modulation of the GABAergic system.

A variety of cerebral insults induce neuronal damage to the hippocampal formation. The somatostatin-immunoreactive (SOM-ir) neurones in the dentate hilus are particularly vulnerable. In the present study, we demonstrated that augmentation of hippocampal GABAergic inhibition by chronic infusion of gamma-vinyl GABA prevented the delayed seizure-induced damage to hilar SOM-ir neurones. Selective lesions of the cholinergic, serotonergic or noradrenergic pathways to the hippocampus did not attenuate the seizure-induced loss of SOM-ir neurones; rather, the damage was exacerbated by the cholinergic lesion. It is, therefore, the intrahippocampal GABAergic circuitries, rather than the selective subcortical pathways, that are critical for neuroprotection after seizures. Enhanced GABAergic inhibition in the hippocampus prevented damage to hilar SOM-ir neurones, even when started 2 days after status epilepticus. GABAergic agents may thus provide an alternative treatment for delayed neuronal damage caused by cerebral insults.

Rectus abdominis muscle flap with microvascular anastomoses for repair of recurrent sarcoma.

After radical resection of a recurrent leiomyosarcoma, the thoracic wall was stabilized with a Gore-Tex graft. The skin and soft tissue defect was repaired with a large rectus abdominis flap in which the circulation was secured by end-to-end microvascular anastomosis of the inferior epigastric artery to the internal mammary artery, which had to be cut during tumor removal.

Infection prophylaxis in pulmonary surgery: a randomized prospective study.

A prospective randomized study to evaluate the efficacy of antibiotic prophylaxis against postoperative infections was carried out on 120 patients undergoing pulmonary operations. The patients were randomized into two groups of 60 patients each. One group received doxycycline (deoxytetracycline) prophylaxis for five days, and the other received cefuroxime (a second-generation cephalosporin) for one day. The groups were comparable with regard to age, sex, common risk factors, diagnosis, and operative procedures. A reduction in the infection rate was noted in the cefuroxime group (10/60) compared with the doxycycline group (19/60), but the difference was not statistically significant (p = 0.055). In major infections (empyema and pneumonia) there was no difference between the groups (4/60 in the cefuroxime group and 5/60 in the doxycycline group), but a significant (p less than 0.05) reduction was noted in minor infections (6/56 and 14/55, respectively) such as lower respiratory tract infections and prolonged fever. There were no wound infections in the two study groups. There were significantly (p less than 0.05) fewer postoperative fever reactions (axillary temperature greater than 37.5 degrees C) in the cefuroxime group (30/60) compared with the doxycycline group (44/60). Both antibiotics were effective in preventing wound infections, but cefuroxime may also be beneficial in preventing minor respiratory infections. The bactericidal effect of cefuroxime may explain this finding.

Normothermic versus mild hypothermic retrograde blood cardioplegia: a prospective, randomized study.

BACKGROUND: Continuous retrograde blood cardioplegia has been introduced as a promising alternative for myocardial protection during cardiac operations, although the optimal conditions for its delivery have been poorly studied. METHODS: We randomized a prospective series of 101 patients to receive either retrograde warm (37 degrees C) or mild hypothermic (28 degrees to 29 degrees C) blood cardioplegia during elective coronary artery bypass grafting. Warm blood cardioplegia was delivered to the aortic root until the heart was arrested, after which the regimen was switched to retrograde and continued either as warm or mild hypothermic cardioplegia. Oxygen consumption and transcardiac pH differences during aortic cross-clamping were determined, and postoperative creatine kinase-MB efflux, hemodynamic recovery, and clinical complications monitored. RESULTS: Clinical characteristics, cardioplegia delivery rates, aortic cross-clamp and cardiopulmonary bypass times, and the number of distal anastomoses were similar in both patient groups. Short intermissions in cardioplegia delivery during construction of distal anastomoses were allowed, the ischemia time in the mild hypothermic group being somewhat longer (8.3% +/- 1.1% versus 5.1% +/- 0.8% of cross-clamp time; p = 0.05). Myocardial oxygen consumption was lower in the mild hypothermic group (2.49 +/- 0.23 versus 3.93 +/- 0.33 mL/min at 30 minutes of cross-clamping; p < 0.01), and the transcardiac pH difference was smaller (0.05 +/- 0.01 versus 0.07 +/- 0.01 at 30 minutes of cross-clamping; p < 0.03). Postoperative creatine kinase-MB levels were higher in the normothermic group. Heart rate was higher and left ventricular stroke work index smaller in the warm group, but otherwise there were no major differences between the groups in hemodynamic recovery. The number of postoperative complications was also similar in both groups. CONCLUSIONS: Although both normothermic (37 degrees C) and mild hypothermic (28 degrees to 29 degrees C) retrograde blood cardioplegia, when delivered in near-continuous fashion, will offer safe myocardial protection during coronary artery bypass grafting, mild hypothermia seemed to provide somewhat better protection under the conditions prevailing here. The effects of different cardioplegia temperatures should perhaps be tested further in patients with recent myocardial infarction, unstable angina, or severely depressed left ventricular function.

Efflux of adenosine and its catabolites during cold blood cardioplegia.

Levels of myocardial high-energy phosphates decrease during cardioplegia for open heart operations, with a subsequent increase in the level of adenosine and its metabolites. It has been demonstrated in experimental models that the effluent concentrations of purines can be used as a measure of the average myocardial energy state. Net adenylate loss and myocardial energy state were evaluated here by determining aorta-coronary sinus differences in levels of adenosine catabolites in 17 patients during cold blood cardioplegia for elective coronary artery bypass grafting. Repeated blood samples were taken before cross-clamping of the aorta, when cardioplegic solute was infused into the aortic root and grafts after five distal anastomoses, and after declamping of the aorta. The aorta-coronary sinus differences in levels of total purines increased 4.7-, 7.5-, 7.1-, 7.8-, and 10.2-fold (from the preclamp level of 1.7 +/- 0.7 mumol/L; p < 0.001) for grafts one through five anastomosed at an average of 19, 34, 50, 63, and 76 minutes after the aortic cross-clamp, respectively. Hypoxanthine and xanthine were present in the highest concentrations. Vasodilatory adenosine concentrations of 1 to 2 mumol/L were observed in the coronary sinus while the aorta was cross-clamped. There was a linear positive correlation between the aorta-coronary sinus purine differences and corresponding cross-clamp time (r = 0.62; p < 0.001). The metabolite differences settled at a more negative level after declamping of the aorta than that prevailing before placement of the cross-clamp, suggesting continuous washout of adenosine and its catabolites during the 30-minute postclamp observation period.(ABSTRACT TRUNCATED AT 250 WORDS)

Computed tomographic evaluation of retrosternal adhesions after pericardial substitution.

BACKGROUND: Reoperative median sternotomy can result in cardiac injury and serious bleeding, with the rate ranging from 2% to 6%. Closure of the native pericardium can maintain a preventing plane of cleavage. In patients in whom primary pericardial closure is not possible, several substitutes have been tried with variable results. We conducted a prospective study to evaluate the clinical feasibility of polytetrafluoroethylene and polyglycolic acid patches as pericardial substitutes, using computed tomography for imaging the postoperative state of the retrosternal space. METHODS: The basic population comprised 540 patients who were scheduled for coronary artery bypass grafting, and 52 of them who met the research criteria were chosen for computed tomographic evaluation after 5 years after the primary operation. RESULTS: As a substitute, polytetrafluoroethylene seemed to be less adhesive to the posterior surface of the sternum. Total adhesion scores were also statistically significant (p < 0.001) to the advantage of polytetrafluoroethylene over polyglycolic acid as a pericardial substitute. CONCLUSIONS: Polytetrafluoroethylene membrane seems to be capable of minimizing retrosternal adhesion formation and thus it may protect the heart during subsequent reoperative sternotomy.

Tiagabine prevents seizures, neuronal damage and memory impairment in experimental status epilepticus.

A novel antiepileptic drug, tiagabine ((R)-N-[4,4-di-(3-methylthien-2-yl) but-3-enyl] nipecotic acid hydrochloride), was studied in rats in order to determine its efficacy in preventing seizures, seizure-induced neuronal damage and impairment of spatial memory in the perforant pathway stimulation model of status epilepticus. In pilot experiments, administration of tiagabine (50, 100 or 200 mg/kg/day) with subcutaneously implanted Alzet osmotic pumps led to a dose-dependent increase in tiagabine concentrations in the serum and brain. Two days of tiagabine treatment at a dose range of 50-200 mg/kg/day did not change the levels of gamma-aminobutyric acid (GABA), glutamate or aspartate in cisternal cerebrospinal fluid (CSF) compared to the controls. In the pentylenetetrazol test, the maximal anticonvulsive effect of tiagabine administered via osmotic pumps was achieved already with a dose of 50 mg/kg/day. In the perforant pathway model of status epilepticus, subchronic treatment with tiagabine (Alzet pumps, 50 mg/kg/day) completely prevented the appearance of generalized clonic seizures during stimulation (P < 0.001). In the same rats, tiagabine treatment reduced the loss of pyramidal cells in the CA3c and CA1 fields of the hippocampus (P < 0.05) but not the loss of somatostatin immunoreactive neurons in the hilus. Two weeks after perforant pathway stimulation, the tiagabine-treated rats performed better in the Morris water-maze test than the vehicle-treated rats did (P < 0.001). Our results show that tiagabine treatment reduces the severity of seizures in the perforant pathway stimulation model of status epilepticus. Possibly associated with the reduction in seizure number and severity, tiagabine treatment also reduced seizure-induced damage to pyramidal cells in the hippocampus as well as the impairment of the spatial memory associated with hippocampal damage.

Effect of lamotrigine treatment on status epilepticus-induced neuronal damage and memory impairment in rat.

Status epilepticus causes neuronal damage that is associated with cognitive impairment. The present study examined whether a novel antiepileptic drug, lamotrigine (LTG), alleviates status epilepticus-induced temporal lobe damage and memory impairment, and compared its efficacy with carbamazepine. Status epilepticus was induced by electric stimulation of the perforant pathway (PP) in rats. Treatment with LTG (12.5 mg/kg, twice a day) was started either 3 days before (preLTG group) or 1 h after (postLTG group) a 60 min PP stimulation. Treatment with carbamazepine (CBZ; 30 mg/kg, twice a day) was started 3 days before (CBZ group) a 60 min PP stimulation. All treatments were continued for 2 weeks. Thereafter, the severity of seizures, seizure-induced neuronal damage, quantitative electroencephalogram (EEG), and memory impairment were compared between vehicle-treated unstimulated and stimulated controls, LTG-treated rats, and CBZ-pretreated rats. Both in the preLTG and postLTG groups, damage to hilar somatostatin-immunoreactive neurons, hippocampal CA3b and CA3a pyramidal cells, and the piriform cortex was mild and did not differ from that in unstimulated controls. Furthermore, CA3c damage in the preLTG group did not differ from that in unstimulated controls. Vehicle-treated stimulated controls and CBZ-pretreated rats, however, had significant damage in the hilus, CA3 subregions, and piriform cortex compared with unstimulated controls (P<0.05 for the stimulated side, contralateral side, or both). Treatment with LTG or CBZ had no effect on the number or duration of behavioral seizures during PP stimulation. They did not affect the baseline EEG or status epilepticus-induced slowing of the EEG. Also, the status epilepticus-induced spatial memory impairment in the Morris water-maze was not attenuated by treatment with LTG or CBZ. Our data demonstrate that treatment with LTG has a mild neuroprotective effect on status epilepticus-induced neuronal damage in rats even when administered after the beginning of status epilepticus.

Neuroprotective effect of remacemide hydrochloride in a perforant pathway stimulation model of status epilepticus in the rat.

Previous studies have demonstrated that remacemide and its desglycinyl metabolite, AR-R 2495AA, reduce neuronal damage in animal models of ischemia, subarachnoid hemorrhage, and traumatic brain injury. The aim of the present study was to investigate whether remacemide hydrochloride also alleviates seizure-induced neuronal damage in a model of status epilepticus induced by the stimulation of the perforant pathway (PP) in the rat. Chronic oral remacemide treatment (3 x 25 mg/kg/day) was started either 2 days before or 2 h after the beginning of PP stimulation (2 mA, 20 Hz, 0.1 ms pulse duration for 60 min). The effects of remacemide treatment on the severity of seizures, electroencephalogram (EEG) parameters, seizure-induced neuronal damage in the temporal lobe regions, and memory impairment were compared to unstimulated and stimulated vehicle-treated controls, and carbamazepine-pre-treated (3 x 40 mg/kg/day) rats. Both remacemide and carbamazepine pretreatments, but not remacemide posttreatment, decreased pyramidal cell damage in the CA3 and CA1 subregions of the hippocampus (P < 0.05). In addition, overall neuronal damage in the extrahippocampal temporal lobe regions (the piriform cortex, entorhinal cortex, and the amygdaloid complex) was milder in remacemide-pretreated rats compared to stimulated control rats (P < 0.01). The neuroprotective effect was most evident on the side contralateral to stimulation. Remacemide or carbamazepine pretreatment had no evident effect on the number or duration of behavioral seizures during PP stimulation. Neither drug altered the spectral parameters of the baseline EEG or prevented status epilepticus-induced EEG slowing observed 2 weeks after PP stimulation. Nor did remacemide or carbamazepine treatment alleviate spatial memory impairment determined in a Morris water-maze task 2 weeks after PP stimulation. Our data provide evidence that pretreatment with remacemide has a moderate neuroprotective effect against status epilepticus-induced neuronal damage.