Biomedical subjects

F Wahl

Publications and source records attributed to F Wahl.

At least 19 recordsLinked to original sources

PubMed2005

Robot-assisted fracture reduction: a preliminary study in the femur shaft.

Reduction in femoral shaft fractures can be difficult to achieve with minimally invasive techniques. Malalignment and high intra-operative radiation exposure can result. The hypothesis was that robot-assisted fracture reduction could improve the quality of reduction while reducing the amount of radiation exposure. A robot system was developed that allows fracture manipulation with a joystick as input device. The system provides the surgeon with haptic and metric feedback. Fifteen synthetic femurs were broken and reduced by simulated open (group A) and closed techniques (group B). These techniques were compared with the robot-assisted reduction with (group C) and without (group D) haptic and metric information. An image intensifier was simulated with two orthogonal cameras. All reduction techniques showed minor malalignment. In group C, the alignment was: procurvatum/recurvatum 0.6 degrees (0-2.0 degrees); varus/valgus 0.8 degrees (0-3.0 degrees); and axial rotation 0.8 degrees (0-3.1 degrees). A significant difference was seen between the groups (two-way ANOVA, p < 0.001). Axial rotation was significantly lower in group C than in group B (1.9 degrees; p < 0.001). The residual varus and valgus deviation was higher in group C compared with group A (0.4 degrees, p = 0.03). The median number of simulated radiographs was significantly less in group C (35) compared with group D (72; p < 0.001) and group B (49; p = 0.01). Robot-assisted fracture reduction of the femur provides high precision in alignment while reducing the amount of intraoperative imaging. Further research in this field is worthwhile.

Femoral Fractures↗

PubMed2001

Assessment of sensorimotor and cognitive deficits induced by a moderate traumatic injury in the right parietal cortex of the rat.

The purpose of this study was to set-up a battery of behavioral tests to assess sensorimotor and cognitive deficits following a moderate traumatic brain injury (TBI) in rats. Coordinated walking ability was evaluated in an accelerated rotarod test. Vestibulomotor function and fine motor coordination were assessed by using a beam-walking task. Rotarod and beam-walking performances were both altered in injured rats compared to sham-operated and control rats. A more pronounced and longer-lasting deficit was measured in the beam-walking test. Cognitive function was studied by using the Lashley maze paradigm. A spatial localization deficit was significant for 4 weeks posttrauma in TBI rats. The beam-walking task and the Lashley maze are robust and sensitive methods in detecting sensorimotor and cognitive impairment after TBI in rats, respectively. These tests are proposed for evaluating the ability of new pharmacological agents to improve the functional recovery after a TBI in rats.

Animals↗

PubMed2001

Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity.

BACKGROUND AND PURPOSE: Heparin and heparinoids have long been proposed for stroke treatment. This study investigates the effect of enoxaparin (Lovenox, Clexane), a low-molecular-weight heparin, on functional outcome (neuroscore) and lesion size in stroke models with reversible and irreversible cerebral ischemia using middle cerebral artery occlusion (MCAO) in the rat. METHODS: Ischemia was induced in rats by transient occlusion for 2 hours or by permanent electrocoagulation of the left MCA. Forty-eight hours after ischemia, neurological deficit was evaluated by scoring sensorimotor functions and ischemic damage was quantified by histological evaluation of lesion volumes. RESULTS: After transient MCAO, enoxaparin at 2x1.5 mg/kg IV (2 and 24 hours after insult) significantly reduced lesion size by 30% (P<0.05) and improved neuroscore (P<0.01). This significant effect on lesion size and neuroscore was still evident when treatment was started 5 hours after insult. Administered under the same protocol with a 5 hours delay post permanent MCAO, enoxaparin reduced lesion size by 49% (P<0.05) and improved neuroscore (P<0.01). CONCLUSIONS: This study indicates that standard nonhemorrhagic doses of enoxaparin reduce ischemic damage with a wide therapeutic window. In addition to its anticoagulant properties, other properties of enoxaparin could act in synergy to explain its neuroprotective profile in ischemia. Thus clinical application of enoxaparin treatment in stroke warrants serious consideration.

Animals↗

PubMed2000

Gas-phase production and photoelectron spectroscopy of the smallest fullerene, C20

Fullerenes are graphitic cage structures incorporating exactly twelve pentagons. The smallest possible fullerene is thus C20, which consists solely of pentagons. But the extreme curvature and reactivity of this structure have led to doubts about its existence and stability. Although theoretical calculations have identified, besides this cage, a bowl and a monocyclic ring isomer as low-energy members of the C20 cluster family, only ring isomers of C20 have been observed so far. Here we show that the cage-structured fullerene C20 can be produced from its perhydrogenated form (dodecahedrane C20H20) by replacing the hydrogen atoms with relatively weakly bound bromine atoms, followed by gas-phase debromination. For comparison we have also produced the bowl isomer of C20 using the same procedure. We characterize the generated C20 clusters using mass-selective anion photoelectron spectroscopy; the observed electron affinities and vibrational structures of these two C20 isomers differ significantly from each other, as well as from those of the known monocyclic isomer. We expect that these unique C20 species will serve as a benchmark test for further theoretical studies.

Journal Article↗

PubMed2000

Enoxaparin reduces brain edema, cerebral lesions, and improves motor and cognitive impairments induced by a traumatic brain injury in rats.

Traumatic brain injury (TBI) is often accompanied by secondary ischemia due, in part, to edema-induced blood vessel compression. Enoxaparin, a low-molecular weight heparin, which is efficacious in models of myocardial and brain ischemia was studied in lateral fluid percussion-induced TBI in rats. Enoxaparin was administered 2 h post-TBI at 0.5 mg/kg i.v. followed by 4 x 0.5, 4 x 1, or 4 x 2 mg/kg s.c. over 30 h. Brain edema was measured in the hippocampus, temporal cortex and parietal cortex. Edema was reduced by enoxaparin (0.5 + 4 x 0.5 mg/kg) in the hippocampus (-53%, p = 0.07) and the parietal cortex (-39%, ns). At 0.5 + 4 x 1 mg/kg edema was reduced in the hippocampus (-63%, p < 0.05) and the parietal cortex (-47%, p = 0.06). At 0.5 + 4 x 2 mg/kg, the reduction was more important in the hippocampus (-69%, p < 0.01) and in the parietal cortex (-50%, p < 0.05). No reduction was seen in the temporal cortex. The lesion size was reduced by enoxaparin at 0.5 + 4 x 1 mg/kg (-50%, p < 0.05), and at 0.5 + 4 x 2 mg/kg (-35%, ns). The neurological deficit evaluated with a 9-point scale was also improved with enoxaparin at 0.5 + 4 x 1 mg/kg 1 week post-TBI (p < 0.05). The cognitive impairment evaluated with a Lashley maze task was improved with enoxaparin (0.5 + 4 x 1 mg/kg) from 48 h (p < 0.05) to 2 weeks post-TBI (p < 0.01). Our results demonstrate for the first time that enoxaparin significantly reduces the brain contusion and edema, and improves the functional outcomes induced by a TBI. Therefore, enoxaparin could be a candidate drug to treat acute brain-injured patients.

Animals↗

PubMed2000

Influence of anesthesia protocol in experimental traumatic brain injury.

Most pharmacologic studies on brain trauma in animals are performed while the animals are under general anesthesia, which can interfere with brain metabolism and modify the experimental results. This study investigates the effects of three anesthetic drugs (halothane 2% and 4%, propofol at 10 mg/kg, and chloral hydrate at 400 mg/kg) on the traumatic brain injury-induced neurologic deficit in mice. Trauma was induced with a weight-drop device. For each drug, animals were divided into four groups; the first did not receive either anesthesia or trauma, the second received anesthesia but no trauma, the third received a trauma without anesthesia, and the fourth received anesthesia before the trauma. A neurologic examination using two different scorings (string and grip test) was performed 1 hour and 24 hours after the trauma. Mortality after trauma was increased for halothane 4% (48% versus 20% in unanesthetized mice), propofol (80% versus 30%), and chloral hydrate (70% versus 44%). Halothane 2% did not increase the mortality in traumatized mice. Halothane 2% or 4% anesthesia did not modify the string score after the trauma. Grip score after the trauma was better in mice anesthetized with halothane at either 2% or 4%. Mice injured under anesthesia with chloral hydrate had worse grip and string scores (P < .05) than unanesthetized mice. These results lead us to question the influence of anesthesia on the results obtained in experimental neuropharmacologic studies, particularly when there are discrepancies between two studies on the same pharmacologic treatment, which differ in their anesthesia protocols.

Anesthesia↗

PubMed1999

Kinetics of polymorphonuclear neutrophil infiltration after a traumatic brain injury in rat.

The aim of our study was to assess polymorphonuclear neutrophil infiltration into the injured parenchyma after a traumatic brain injury (TBI). Myeloperoxidase (MPO) activity was assayed on the hippocampus, temporal and parietal cortex 6, 24, 48, 72, and 120 h post-trauma. MPO activity occurred in these structures from 6 h post-trauma and was maximum at 24-48 h. It was resolved by 72 h in the hippocampus and the parietal cortex, but persisted in the temporal cortex until 120 h after trauma. This suggests that neutrophil infiltration is a delayed phenomenon in the physiopathology of TBI. Considering that a large therapeutic window may be crucial in the management of TBI, inhibition of neutrophil infiltration needs to be further investigated following cerebral trauma.

Animals↗

PubMed1999

Neuroprotective effects of riluzole in neurotrauma models: a review.

Physical injury to the central nervous system (CNS) remains one of the main causes of mortality and disability in young adults. Numerous therapies have been successfully evaluated in experimental traumatic brain or spinal cord injuries (TBI, SCI) and, although some of them are currently under clinical trials for these indications, no drug therapy is at present available. Thus, an interesting approach to reduce the CNS injury-induced damage could be the blockade of Na(+)-channels by drugs such as riluzole which is neuroprotective in models of TBI or SCI as summarized in this review. Repeated doses ranging from 2 to 8 mg/kg were administered between 24 h to 10 days post-injury, with a first administration given either at 15 min or up to 6 h post-injury. In these models riluzole was found to reduce both the size of spinal cord and brain lesions as well as brain edema, and to restore the neurological, motor and cognitive impairments consequent of these injuries. The largest therapeutic time window obtained was 1 to 6 h in TBI. This such a compound should be considered as an interesting candidate for the treatment or SCI or TBI.

Animals↗

PubMed1998

Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat.

The neuroprotective effects of Riluzole, a compound with several mechanisms of action including the inhibition of sodium channel activity and glutamate release, were evaluated in a rat model of parasagittal fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to parasagittal FP brain injury of moderate severity (2.3-2.5 atm). Fifteen min following injury, animals randomly received an i.v. bolus of either Riluzole (8 mg/kg, n = 8) or vehicle (n = 9), followed by subcutaneous injections (identical dose) at 6 hr and 24 hr. Two weeks after injury and drug treatment, animals were sacrificed and a series of brain sections, stained with Hematoxylin and Eosin (H&E) or cresyl violet, were evaluated for quantitative cortical lesion volume and cell counts of hippocampal CA3 neurons, respectively, using a computerized image analysis system. Administration of Riluzole significantly reduced FP-induced tissue loss in the temporal/occipital cortices ipsilateral to the site of impact by 46%, compared to vehicle-treated, brain-injured animals (P = 0.01). In contrast, the selective neuronal loss observed in the CA3 region of the ipsilateral hippocampus was unaffected by Riluzole treatment. The present study demonstrates that Riluzole can attenuate cortical lesion size following brain trauma. These neuroprotective effects may be related to the synergy of the different mechanisms of action of Riluzole.

Animals↗

PubMed1997

Riluzole reduces brain lesions and improves neurological function in rats after a traumatic brain injury.

Riluzole (2-amino 6-trifluoromethoxy-benzothiazole) was studied in a rat model of traumatic brain injury (TBI) induced by a fluid percussion applied laterally to the right parietal cortex. Study I: vehicle or riluzole (4 or 8 mg/kg) was administered 15 min (i.v.), 6 h and 24 h (s.c.), after TBI. Brain lesions were quantified 1 week after insult. Riluzole significantly reduced the size of TBI-induced lesions by approximately 44% with either dose regime (P < 0.05). Study II: vehicle or riluzole (8 mg/kg) was administered 15 min (i.v.), 6 h (i.p.) and then twice daily (i.p.) for 6 days, after injury. One, 2 and 3 weeks after TBI, a neurological examination was performed. Control injured rats had a significant neurological deficit at 1, 2 and 3 weeks (P < 0.001). Riluzole treatment did not modify the neurological status evaluated for the first 2 weeks after TBI. However at 3 weeks, riluzole significant improved the neurological function of injured rats (P < 0.05). These results suggest that riluzole may be beneficial in the clinical treatment of TBI. The protective action of riluzole may result from (i) stabilization of the inactivated state of voltage-dependent sodium channels, (ii) indirect action on the glutamatergic pathway, and/or (iii) indirect neurotrophic effect.

Animals↗

PubMed1997

Riluzole reduces incidence of abnormal movements but not striatal cell death in a primate model of progressive striatal degeneration.

Riluzole has been shown recently to increase life expectancy in patients with amyotrophic lateral sclerosis. A number of experimental studies also suggest that this compound may be a neuroprotectant. We have investigated in baboons whether riluzole would protect striatal neurons from a prolonged 3-nitropropionic acid (3NP) treatment and ameliorate the associated motor symptoms. In animals receiving 3NP and the solvent of riluzole, 12 weeks of high-dose 3NP treatment resulted in the appearance of persistent leg dystonia and significant increases in the incidence of three categories of abnormal movements and in the dyskinesia index in the apomorphine test (0.5 mg/kg i.m.). Quantitative assessment of these behavioral deficits using a video movement analysis system demonstrated a significant decrease in locomotor activity and peak tangential velocity in 3NP-treated animals compared to controls. Histological analysis showed the presence of severe, bilateral, striatal lesions, localized in both caudate and putamen. Cotreatment with riluzole (4 mg/kg i.p., twice daily) significantly reduced the dyskinesia index (-35%, P < 0.02) in the apomorphine test. In the quantitative behavioral analysis, riluzole significantly ameliorated the decrease in peak tangential velocity (P < 0.02) but not the decrease in locomotor activity observed after 3NP. Comparative histological analysis of the two groups of treated animals did not demonstrate a clear neuroprotective effect of riluzole. The present study suggests that one potential therapeutic interest for riluzole in neurodegenerative disorders may reside in the reduction of motor symptoms associated with striatal lesions.

Acetylcholinesterase↗

PubMed1997

Effects of riluzole on the evolution of focal cerebral ischemia: a magnetic resonance imaging study.

The aim of this study was to investigate the effects of riluzole on the lesion induced by a permanent middle cerebral artery occlusion (MCAO) in rats. Riluzole at 4 or 8 mg/kg i.v. significantly reduced the cortical ischemic brain damage. With the most effective dose of 8 mg/kg, the time evolution of the lesion was assessed by T2-weighted magnetic resonance imaging (MRI) repeated on the same animals after MCAO. MRI obtained at 24, 48, and 72 hours after MCAO showed a progressive increase of the ischemic lesion, except in the cortex of the riluzole-treated rats (8 mg/kg i.v.). Furthermore, there was no difference between lesion volumes as measured by MRI or by histology. This study indicates that MRI may be a valuable method to quantify in vivo the neuroprotective profile of a drug.

Animals↗

PubMed1997

Time course of cerebral edema after traumatic brain injury in rats: effects of riluzole and mannitol.

Brain trauma is the main cause of morbidity and mortality in young adults. One delayed events that occurs after a head trauma and compromises the survival of patients is cerebral edema. The present study examined first the occurrence of cerebral edema after a traumatic brain injury (TBI) induced by moderate fluid percussion in rats. Brain water content was measured from 1 h to 7 days posttrauma, in the hippocampus and cortex, on both ipsi- and contralateral hemispheres. Second, the effects of mannitol, an osmotic agent frequently used in the clinic, and riluzole, a neuroprotective compound, were investigated on regional edema formation. After TBI, the ipsilateral edema began early at 1-6 h, was maximal at 48 h and was resorbed by 5-7 days. No edema was observed in the contralateral hemisphere. Mannitol at 1 g/kg or vehicle was administered iv 15 min, 2 h and 4 h postinjury. At this dose, mannitol significantly attenuated the ipsilateral injured cortex edema measured at 6 h (p < 0.05). Riluzole at 4 and 8 mg/kg or vehicle was administered 15 min (IV) and 6 h, 24 h, and 30 h (SC) post-TBI. Riluzole at 4 x 4 mg/kg significantly reduced edema measured at 48 h, in the ipsilateral hippocampus (p < 0.05), whereas at 4 x 8 mg/kg, the reduction was observed in the hippocampus (p < 0.01) and the injured cortex (p < 0.05). Our results demonstrate that (1) cerebral edema begins early after the injury and is resorbed over 1 week; (2) mannitol could attenuate cerebral edema; and (iii) riluzole in addition to its neuroprotective effects reduces the brain edema. Thus, riluzole could be useful in human TBI treatment.

Animals↗

PubMed1995

Effect of riluzole on quinolinate-induced neuronal damage in rats: comparison with blockers of glutamatergic neurotransmission.

Intrastriatal injection of quinolinate, an N-methyl-D-aspartate (NMDA) agonist, induces a local neuronal lesion, and provides an excitotoxic model of Huntington's disease. In this study, we investigated the effect of different agents acting at various levels of the glutamatergic neurotransmission: (i) dizocilpine (MK801) (0.5 mg/kg ip) significantly reduced the lesion by 74%; (ii) 6-(1-imidazolyl)-7-nitroquinoxaline-2,3(1H,4H)-dione (YM-90K) (3 x 10 and 3 x 20 mg/kg ip) and (iii) lamotrigine (50 mg/kg ip) had no effect; (iv) riluzole (4 and 8 mg/kg per os) significantly reduced the lesion by 35%. The inefficiency of YM-90K suggested that alpha-amino-3-hydroxy-5-methylisoxasole-4-propionate (AMPA) receptors do not participate to the quinolinate-induced excitotoxicity. The mechanism of action of riluzole may be related also to a combination of its different properties. This study indicates that riluzole may be useful for treatment of Huntington's disease.

Animals↗

PubMed1994

Extracellular glutamate during focal cerebral ischaemia in rats: time course and calcium dependency.

The time course of changes in extracellular glutamic acid levels and their Ca2+ dependency were studied in the rat striatum during focal cerebral ischaemia, using microdialysis. Ischaemia-induced changes were compared with those produced by high K(+)-evoked local depolarization. To optimize time resolution, glutamate was analysed continuously as the dialysate emerged from the microdialysis probe by either enzyme fluorimetry or biosensor. The Ca2+ dependency of glutamate changes was examined by perfusing the probe with Ca(2+)-free medium. With normal artificial CSF, ischaemia produced a biphasic increase in extracellular glutamate, which started from the onset of ischaemia. During the first phase lasting approximately 10 min, dialysate glutamate level increased from 5.8 +/- 0.9 microM.min-1 to 35.8 +/- 6.2 microM where it stabilized for approximately 3 min. During the second phase dialysate glutamate increased progressively to its maximum (82 +/- 8 microM), reached after 55 min of ischaemia, where it remained for as long as it was recorded (3 h). The overall changes in extracellular glutamate were similar when Ca2+ was omitted from the perfusion medium, except that the first phase was no longer detectable and, early in ischaemia, extracellular glutamate increased at a significantly slower rate than in the control group (2.2 +/- 1 microM.min-1; p < 0.05). On the basis of these data, we propose that most of the glutamate released in the extracellular space in severe ischaemia is of metabolic origin, probably originating from both neurons and glia, and caused by altered glutamate uptake mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1993

Involvement of dopaminergic receptors in quinolinate-induced striatal lesions.

The purpose of this study was to examine the effects of blockade (sulpiride) and activation (quinpirole) of dopaminergic D2 (DA2) receptors on brain lesions subsequent to excessive activation of glutamate (GLU) receptors. Striatal lesions were produced by direct injection of quinolinic acid, an endogenous GLU receptor agonist. Sulpiride (100 mg kg-1 i.p., 30 min before quinolinic acid injection and 1 h after) significantly (p < or = 0.05) reduced the volume of the lesion by around 20%. Quinpirole (1.25 mg kg-1 i.p., 30 min before quinolinic acid injection) had no effect. The protective action of DA2 receptor blockade strongly suggests that quinolinic acid-induced excitotoxicity may be partly modulated by DA2 receptors.

Animals↗

PubMed1993

Effect of riluzole on focal cerebral ischemia in rats.

The effects of riluzole, a putative inhibitor of glutamate release, on the histological and neurobehavioral consequences of middle cerebral artery occlusion were tested in Sprague-Dawley rats. Neurobehavioral studies (neurological examination, passive avoidance task) were carried out with sham-operated and occluded rats. Riluzole 4 and 8 mg/kg administered 30 min after occlusion reduced (P < 0.01) the cortical infarct (respectively 94 +/- 12 mm3 and 73 +/- 15 mm3 versus 139 +/- 8 mm3 for control rats). Striatum necrosis was not modified by the low dosage (46 +/- 3 mm3 versus 49 +/- 3 mm3 for control rats), whereas the high dosage increased it (61 +/- 3 mm3, P < 0.05). The ischemia-induced neurological and memory impairments were not improved by riluzole. Our results indicate that a drug depressing glutamatergic neurotransmission without blocking the glutamate receptors exerts anti-ischemic activity. Moreover, the results highlight the need for carrying out histological and neurobehavioral studies in parallel in this model.

Anesthetics↗

PubMed1992

Neurological and behavioral outcomes of focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: The aim of this study was to investigate the neurobehavioral consequences of focal ischemia in rats. METHODS: We induced permanent occlusion of the left middle cerebral artery in 14 Sprague-Dawley rats, and used 13 sham-operated rats as controls. During surgery, brain temperature and body temperature were kept at normothermia. Neurobehavioral studies (neurological examination, passive avoidance task, Y maze test, and modified open-field test) were carried out 4 days after ischemia before killing the rats to evaluate histological damage. RESULTS: Ischemia induced large infarcts in the cortex (138.6 +/- 8.5 mm3) and caudate-putamen (48.8 +/- 2.6 mm3) and, compared with sham-operated rats, produced a dramatic neurological deficit (p less than 0.001) characterized by sensorimotor dysfunctions and hemiplegia. Memory retention was significantly (p less than 0.05) impaired in the passive avoidance task, but neither vigilance and exploratory behavior measured in the modified open-field test nor working memory evaluated in the Y maze test were disturbed. Infarct size was not correlated with the neurological or behavioral deficits. CONCLUSIONS: This lack of correlation indicates the necessity of carrying out parallel histological, neurological, and behavioral studies in any assays of new drugs using this model of focal ischemia.

Animals↗