Biomedical subjects

C E Gross

Publications and source records attributed to C E Gross.

At least 37 records · Page 2Linked to original sources

PubMed2000

16(R)-hydroxyeicosatetraenoic acid, a novel cytochrome P450 product of arachidonic acid, suppresses activation of human polymorphonuclear leukocyte and reduces intracranial pressure in a rabbit model of thromboembolic stroke.

OBJECTIVE: Activated polymorphonuclear leukocytes (PMNs) have been suggested to contribute to the development of increased intracranial pressure (ICP). We recently demonstrated that human PMNs produce a novel cytochrome P450-derived arachidonic acid metabolite, 1 6(R)-hydroxyeicosatetraenoic acid [16(R)-HETE], that modulates their function. It was thus of interest to examine this novel mediator in an acute stroke model. METHODS: 16-HETE was assessed initially in a variety of human PMN and platelet in vitro assays and subsequently in an established rabbit model of thromboembolic stroke. A total of 50 rabbits completed a randomized, blinded, four-arm study, receiving 16(R)-HETE, tissue plasminogen activator, both, or neither. Experiments were completed 7 hours after autologous clot embolization. The primary end point for efficacy was the suppression of increased ICP. RESULTS: In in vitro assays, 16(R)-HETE selectively inhibited human PMN adhesion and aggregation and leukotriene B4 synthesis. In the thromboembolic stroke model, animals that received 16(R)-HETE demonstrated significant suppression of increased ICP (7.7 +/- 1.2 to 13.1 +/- 2.7 mm Hg, baseline versus final 7-h time point, mean +/- standard error), compared with either the vehicle-treated group (7.7 +/- 0.9 to 15.8 +/- 2.6 mm Hg) or the tissue plasminogen activator-treated group (7.6 +/- 0.6 to 13.7 +/- 2.1 mm Hg). The group that received the combination of 16(R)-HETE plus tissue plasminogen activator demonstrated no significant change in ICP for the duration of the protocol (8.6 +/- 0.6 to 11.1 +/- 1.2 mm Hg). CONCLUSION: 16(R)-HETE suppresses the development of increased ICP in a rabbit model of thromboembolic stroke and may serve as a novel therapeutic strategy in ischemic and inflammatory pathophysiological states.

Animals↗

PubMed1999

Absence of MPTP-induced neuronal death in mice lacking the dopamine transporter.

MPTP has been shown to induce parkinsonism both in human and in nonhuman primates. The precise mechanism of dopaminergic cell death induced following MPTP treatment is still subject to intense debate. MPP+, which is the oxidation product of MPTP, is actively transported into presynaptic dopaminergic nerve terminals through the plasma membrane dopamine transporter (DAT). In this study, we used mice lacking the DAT by homologous recombination and demonstrated that the MPTP-induced dopaminergic cell loss is dependent on the presence of the DAT. For this we have used tyrosine hydroxylase immunoreactivity (TH-IR) labeling of dopamine cells of the substantia nigra compacta in wild-type, heterozygote, and homozygote mice that were given either saline or MPTP treatments (two ip injections of 30 mg/kg, 10 h apart). Our results show a significant loss of TH-IR in wild type (34.4%), less loss in heterozygotes (22.5%), and no loss in homozygote animals. Thus dopamine cell loss is related to levels of the DAT. These results shed light on the degenerative process of dopamine neurons and suggest that individual differences in developing Parkinson's disease in human may be related to differences of uptake through the DAT of a yet unidentified neurotoxin.

Animals↗

PubMed1999

Effect of the alpha 2 adrenoreceptor antagonist, idazoxan, on motor disabilities in MPTP-treated monkey.

1. The motor effect of the alpha 2 adrenoreceptor antagonist, idazoxan, was compared to that of L-dopa in MPTP-treated monkeys. 2. Idazoxan 2.0 mg/kg improved parkinsonian motor abnormalities which was comparable to the effects of a minimal effective dose of L-dopa. 3. At 2.0 and 5.0 mg/kg, the parkinsonian rigidity was the item most frequently alleviated by idazoxan (respectively 63.6% and 68.2%). 4. These findings provide support for the therapeutic utility of alpha 2 antagonists in the treatment of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1999

From experimentation to the surgical treatment of Parkinson's disease: prelude or suite in basal ganglia research?

Parkinson's disease remains one of the greatest challenges facing those who work in the field of neurological research. Although the development of levodopa treatment revolutionised management of this debilitating diseases, no effective long-term therapy has yet been found. With recent advances in the understanding of basal ganglia physiopathology and the experimental demonstration of the efficacy of certain surgical procedures, there is a renewed interest in the surgical approach. This paper provides a chronological overview of the history of parkinsonian surgery and discusses the principal surgical options at our disposal today. These take three main forms: ablation (thalamotomy, pallidotomy and subthalamotomy); cell graft and gene therapy (mainly in the striatum); and deep brain stimulation (of the thalamus, globus pallidus pars internalis and the subthalamic nucleus). Our knowledge of basal ganglia function and our conception of how motor information is processed by this network have evolved parallel to the development of surgical techniques. Recent results from both clinical and experimental studies underline the complexity of the physiopathological mechanisms which generate parkinsonian symptomatology and lead us to question our assumption that each class of clinical signs (tremor, akinesia, rigidity, levodopa-induced dyskinesias...) is produced by a specific and separate mechanism. In the same way, comparison of the electrophysiological and biochemical effects of the different techniques induced in brain function vary considerably. This complex world of interaction and interconnection is a labyrinth that we are still far from comprehending in its entirety. All the more reason, in consequence, for extending experimental investigation into the impact of any new therapy before proposing its clinical application.

Animals↗

PubMed1999

Complement depletion does not reduce brain injury in a rabbit model of thromboembolic stroke.

The contribution of the complement system to cerebral ischemic and ischemia/reperfusion injury was examined in a rabbit model of thromboembolic stroke by delivery of an autologous clot embolus to the intracranial circulation via the internal carotid artery. A two-by-two factorial design was employed to study the impact of complement depletion via pretreatment with cobra venom factor (CVF, 100 U/kg i.v.) in the setting of permanent (without tissue plasminogen activator; t-PA) and transient (with t-PA) cerebral ischemia. Thirty-two New Zealand white rabbits were assigned to one of four groups (n=8, each group): control without t-PA, control with t-PA, CVF without t-PA and CVF with t-PA. In the complement intact animals, t-PA administration resulted in an approximate 30% reduction in infarct size when compared to the group not receiving t-PA (20.4+/-6.6% of hemisphere area vs. 30.1+/-7.2%; mean+/-SEM). However, infarct sizes in the complement depleted rabbits, with (30.7+/-8.2%) or without (30.2+/-7.9%) t-PA, were no different from the control group receiving no therapy. Similarly, no difference in regional cerebral blood flow or final intracranial pressure values was noted between any of the four groups. Complement activation does not appear to be a primary contributor to brain injury in acute thromboembolic stroke.

Animals↗

PubMed1999

Involvement of the subthalamic nucleus in glutamatergic compensatory mechanisms.

The purpose of the present study was to investigate whether the subthalamic nucleus (STN) was implicated in the glutamatergic compensatory mechanisms which have been shown to mask the parkinsonian motor abnormalities at the end of the presymptomatic period in experimental parkinsonism. Using multiunit electrophysiological recordings, we follow changes of activity occurring in the STN and in both the pars externalis and the pars internalis of the globus pallidus of monkeys chronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), according to a protocol designed to mimic the gradual evolution of dopaminergic neuronal death. STN activity augmented significantly in the course of treatment, even before the first appearance of clinical signs (P < 0.01). This result would indicate that the STN, which increases its level of activity even before the end of the presymptomatic period, is principally responsible for the instigation of glutamatergic compensatory mechanisms which allow the maintenance of the striatal dopaminergic homeostasis.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1999

Antiplatelet therapy in acute cerebral ischemia.

BACKGROUND: Improved recognition of stroke signs and symptoms has paralleled the development of pharmacological strategies that may be examined to reduce stroke mortality and morbidity. Presently, tissue plasminogen activator is the only therapy that significantly improves outcome in acute stroke, with no agent demonstrating a significant reduction in mortality. SUMMARY OF REVIEW: Antiplatelet agents are a heterogenous class of drugs that have been successfully used for more than 2 decades in secondary stroke prevention. These agents include aspirin, with or without dipyridamole, and more recently, the adenosine antagonists ticlopidine and clopidogrel. However, studies of the use of antiplatelet agents within 48 hours of the ictus have examined only aspirin. Only 1 study, the Multicentre Acute Stroke Trial-Italy (MAST-I), entered patients within 6 hours of the ictus. These data suggest that an improvement in mortality may be related to the speed of administration. No significant adverse events were noted with early antiplatelet monotherapy. However, MAST-I did note a significant increase in early mortality in patients receiving aspirin plus streptokinase, a finding not adequately explained by an increase in the intracranial hemorrhage rate. CONCLUSIONS: The use of antiplatelet therapy in acute stroke, clinical or experimental, has only recently received attention. It is likely that the use of antiplatelet agents for acute stroke therapy will be less restrictive than that currently seen for thrombolytics. Future studies should include an examination of those agents that have previously demonstrated efficacy in secondary stroke prevention, most notably, aspirin. The recognition that all platelet stimuli share a final common pathway that is dependent on the surface glycoprotein IIb/IIIa (fibrinogen) receptor has resulted in the development of various agents which block this receptor and are currently the focus for clinical trials. The role of nitric oxide in stroke therapy will depend on minimizing the hypotensive side effects of this agent. Stroke models are needed to provide preliminary data on the efficacy of antiplatelet therapy, especially as relates to the interaction of antiplatelet agents with thrombolytics.

Acute Disease↗

PubMed1999

Treatment of basilar artery bifurcation aneurysms by using Guglielmi detachable coils: a 6-year experience.

OBJECT: The authors retrospectively analyzed the results of their 6-year experience in the treatment of basilar artery (BA) bifurcation aneurysms by using Guglielmi detachable coils (GDCs). METHODS: This analysis involved 45 BA tip aneurysms in 16 men and 29 women who ranged in age from 23 to 78 years (mean 50 years). Seventy-five percent of the aneurysms had ruptured and 25% remained unruptured. Of the group whose aneurysms hemorrhaged, 14 patients were Hunt and Hess Grade I or II and 20 were Hunt and Hess Grades III to V; 32 patients were treated within 2 weeks of their subarachnoid hemorrhage (SAH). Initially, treatment with GDCs was limited to poor-grade high-risk patients who refused surgery or patients in whom surgery proved unsuccessful. Later in the study, good-grade patients with narrow-necked aneurysms were also treated using GDCs. The length of clinical follow up ranged from 1 to 72 months (average 27.4 months) in the 37 surviving patients. In 33 of the 45 aneurysms treated with coil placement, good to excellent results were achieved. There were 12 poor results (27%) including one in a patient from the non-SAH group who suffered a thrombotic complication due to an underlying vasculitis. Eight deaths were recorded in this group of 45 patients. One of these deaths was caused by a complication related to anesthesia, one by unknown causes, and six resulted from complications of the disease. One patient rebled on the 2nd day after the endovascular procedure. The mortality and permanent morbidity rates directly related to the intervention were 2.2% and 4.4%, respectively. Angiographic studies obtained immediately postintervention demonstrated 99 to 100% occlusion in 30 (67%) of the aneurysms; nine (20%) were more than 90% occluded; and six (13%) were less than 90% occluded by the GDCs. Follow-up angiograms were obtained in 31 patients between 2 and 72 months after coil placement. Nineteen (61%) of the follow-up angiograms revealed stable results (that is, no change from initial treatment). Twelve of the 31 showed coil compaction, but only eight of these lesions could accept additional coils. In large aneurysms recanalization was seen in 57%, and some of the larger lesions required as many as four embolizations (mean 1.7) to achieve optimal occlusion. When small-necked aneurysms were analyzed as a subset, a stable angiographic result was seen in 92%. CONCLUSIONS: Use of GDCs led to excellent clinical and angiographic results in the majority of patients with BA tip aneurysms included in this limited follow-up study. Rebleeding was encountered in one of the 34 previously ruptured BA aneurysms treated with GDCs, and no hemorrhages have been documented in the 11 unruptured aneurysms treated with GDCs in this series. Long-term follow-up studies are necessary before it is possible to compare adequately the treatment of aneurysms with coil placement to the gold standard of aneurysm clipping.

Adult↗

PubMed1999

Gross and microscopic histopathological findings in aneurysms of the human brain treated with Guglielmi detachable coils.

OBJECT: The histopathological characteristics of aneurysms obtained at autopsy or surgery 3 days to 54 months after being treated with Guglielmi detachable coils (GDCs) were assessed. METHODS: Seventeen aneurysms were obtained at autopsy and one was removed at surgery. Fourteen were examined histologically with the coils in situ. Naked coils embedded in an unorganized thrombus were found in those aneurysms that had been treated with coils within 1 week earlier. An incomplete replacement of the intraluminal blood clot by fibrous tissue and a partial membranous covering at the aneurysm orifice were observed in those aneurysms that had been treated with coils between 2 and 3 weeks prior to examination. One small aneurysm treated 6 weeks before harvesting showed formation of an endothelium-lined layer of connective tissue at the orifice. Collagen-rich vascularized tissue surrounding the coils was found in an aneurysm removed at surgery 54 months after coil implantation. Interestingly, six (50%) of 12 aneurysms (two small, three large, and one giant) that had been deemed 100% occluded on initial angiography showed tiny open spaces between the coils at the neck on gross examination. CONCLUSIONS: Endothelialization of the aneurysm orifice following placement of GDCs can occur; however, it appears to be the exception rather than the rule. In large aneurysms the process of intraaneurysm clot organization seems to be delayed and incomplete; tiny open spaces between the coils and an incomplete membranous covering in the region of the neck are frequently encountered. Further longitudinal studies are required to establish the spectrum of healing profiles that may direct our efforts in modifying the GDC system to produce a more stable long-term result.

Adult↗

PubMed1999

Aspirin reduces experimental cerebral blood flow in vivo.

Aspirin therapy for stroke prophylaxis in low risk patients has paradoxically demonstrated an increased risk of ischemic stroke in several studies. Moreover, the MAST-Italy trial reported a near doubling of mortality with the addition of aspirin to thrombolytics while experimentally, we have noted that aspirin antagonizes t-PA-mediated clot lysis. The mechanisms responsible for these observations is unclear. Of interest, few studies have examined the effect of aspirin on cerebral blood flow (CBF). The objective of this study was to examine the acute effect of high dose aspirin on CBF in a rabbit model. Mean arterial pressure, arterial blood gases, and core and brain temperature were controlled throughout the protocol. CBF, measured by the technique of hydrogen clearance using Platinum-Iridium flow probes, was measured before and 20 min following aspirin administration (20 mg kg-1 i.v.) in a cohort of 50 rabbits and compared to rabbits receiving vehicle (n = 19). Following aspirin therapy, CBF (cc/100 g-1 min-1) was reduced from 80.8 +/- 27.4 to 65.1 +/- 31.7 (mean +/- SD), a reduction to 80.4 +/- 21.3% of baseline (p < 0.00001, t-test), whereas CBF in the control group remained unchanged (81.0 +/- 25.4 vs. 77.5 +/- 24.0, mean +/- SD). Thus aspirin acutely reduced CBF by approximately 20% in a rabbit model, perhaps related to inhibitory effects on prostacyclin and/or nitric oxide. This result may help explain the possible increase in ischemic stroke seen in low risk patients on aspirin therapy. A reduction in CBF by aspirin may also assist in understanding the antagonism of t-PA-mediated clot lysis by aspirin seen in our rabbit model of thromboembolic stroke, particularly since all agents which share the ability to reverse this antagonism (nitric oxide donors, beta blockers, hydralazine, prostacyclin) also increase CBF by approximately 20%. Future strategies for 'antiplatelet' therapy may benefit from using agents which do not adversely affect CBF.

Animals↗

PubMed1998

Riluzole delayed appearance of parkinsonian motor abnormalities in a chronic MPTP monkey model.

Preliminary studies have shown that riluzole, a Na+ channel blocker with antiglutamatergic activity, has neuroprotective efficacy in several models of acute dopaminergic neurodegeneration. A chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model which comes closer to the slow evolution of Parkinson's disease has recently been developed in order to allow dynamic studies. The present results show that riluzole delayed the appearance of parkinsonian motor abnormalities in this dynamic model, using from 10.2 +/- 1.6 daily injections for the MPTP-treated monkeys (n = 4) to 16.5 +/- 2.0 daily injections for the MPTP + riluzole-treated monkeys (n = 4). These results strongly suggest that riluzole may be beneficial to slow down the rate of progression of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Glutamatergic compensatory mechanisms in experimental parkinsonism.

1. Injection cannulae allowing access to the SNc were implanted bilaterally in four monkeys. Once animals had recovered from the operation, daily low-dose treatment with MPTP was started. 2. Group I comprised two monkeys under treatment with MPTP, but still asymptomatic. Group II comprised two monkeys treated with MPTP and presenting clinical symptoms. 3. Both groups received daily intracranial injections of kynurenic acid in order to block the glutamatergic afferents to the SNc. 4. In the first group of asymptomatic monkeys, kynurenic acid induced parkinsonian motor abnormalities. In the second group of symptomatic monkeys, it increased the severity of clinical signs. 5. Glutamatergic inputs to the SNc would therefore appear to be implicated in compensatory phenomena at different stages of experimental parkinsonism.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1998

Compensatory mechanisms in experimental and human parkinsonism: towards a dynamic approach.

This paper provides an overview of the compensatory mechanisms which come into action during experimental and human parkinsonism. The intrinsic properties of the dopaminergic neurones of the substantia nigra pars compacta (SNc) which degenerate during Parkinson's disease are described in detail. It is generally considered that the nigrostriatal pathway is principally responsible for the compensatory preservation of dopaminergic function. It is also becoming clear that the morphological characteristics of dopaminergic neurones and the dual character, synaptic and asynaptic, of striatal dopaminergic innervation engender two modes of transmission, wiring and volume, and that both these modes play a role in the preservation of dopaminergic function. The plasticity of the dopamine neurones, extrinsic or intrinsic to the striatum, can thus be regarded as another compensatory mechanism. Recent anatomical and electrophysiological studies have shown that the SNc receives both glutamatergic and cholinergic inputs. The dynamic role this innervation plays in compensatory mechanisms in the course of the disease is explained and discussed. Recent developments in the field of compensatory mechanisms speak for the urgence to develop a valid chronic model of Parkinson's disease, integrating all the clinical features, even resting tremor, and illustrating the gradual evolution of nigral degeneration observed in human Parkinson's disease. Only a dynamic approach to the physiopathological study of compensatory mechanisms in the basal ganglia will be capable of elucidating these complex questions.

Adaptation, Physiological↗

PubMed1998

Humanized anti-L-selectin monoclonal antibody DREG200 therapy in acute thromboembolic stroke.

Strategies directed against activated neutrophils have reduced ischemia-induced brain injury. However, therapies targeted specially against the neutrophil adhesion protein L-selectin have not yet been examined in stroke. This study therefore examined the effects of a monoclonal antibody directed against L-selectin in a rabbit model of thromboembolic stroke with (n = 16) or without (n = 10) concomitant t-PA therapy. Rabbits received either the humanized monoclonal antibody DREG200 directed against the L-selectin receptor or humanized control monoclonal antibody HuDREG55 which does not bind to rabbit L-selectin in addition to t-PA therapy (n = 8, each group). HuDREG200 (2 mg kg-1 i.v.) was given as a bolus 3 h following clot embolization, followed immediately by a 2 h intravenous infusion of t-PA (6.3 mg kg-1. Without t-PA therapy rabbits received HuDREG200 (2 mgkg-1, i.v.; n = 5) or HuDREG55 (n = 5) 1 h following clot embolization. The group receiving HuDREG200 in addition to t-PA demonstrated a moderate improvement in brain infarct size (8.4 +/- 2.4 vs. 13.5 +/- 3.5, %hemisphere, mean +/- sem), ICP (final reading 10.0 +/- 1.6 vs. 12.4 +/- 3.0 torr) and restoration in regional cerebral blood flow (30.2 +/- 7.8 vs. 21.6 +/- 10.9 cc 100 g-1 min-1) when compared to t-PA therapy alone although statistical significance was not achieved. No efficacy was demonstrated in the group receiving HUDREG200 without concomitant t-PA therapy. The results suggest the addition of a humanized anti-L-selectin monoclonal antibody HuDREG200 in combination with t-PA may further improve outcome in acute thromboembolic stroke, although future studies are necessary to support these findings.

Acute Disease↗

PubMed1998

Preoperative volume expansion improves tolerance to carotid artery cross-clamping during endarterectomy.

OBJECTIVE: The benefit of carotid endarterectomy for carotid artery stenosis relates to both appropriate patient selection and careful surgical technique. Critical to the latter is the ability to afford intraoperative neuroprotection during carotid cross-clamping, although the optimal strategy to assure this protection remains debated. This report describes the impact of adding preoperative colloid volume expansion to a surgical algorithm that includes electroencephalographic (EEG) monitoring and barbiturate-induced burst suppression for EEG lateralization refractory to hypertension. METHODS: The incidence of ischemic EEG change during carotid cross-clamping was observed. The results of an initial series of patients (n = 45) reported before incorporation of volume expansion were compared with the results of the current series (n = 155) of carotid endarterectomies, which included preoperative volume expansion with 6% hetastarch (500 or 1000 cc). RESULTS: With preoperative volume expansion, there was a 40% decrease in the incidence of EEG lateralization during carotid cross-clamping (17.4 versus 28.9%, P < 0.05) and a 63% decrease in the EEG lateralization refractory to induced hypertension (5.8 versus 15.6%, P < 0.05). The combined perioperative stroke and death rate was 1.3%. CONCLUSION: These results support the use of preoperative colloid volume expansion in carotid endarterectomy as a means of increasing the cerebral tolerance to carotid cross-clamping.

Adjuvants, Anesthesia↗

PubMed1998

Experimental models of Parkinson's disease: from the static to the dynamic.

The experimental models of Parkinson's disease (PD) available today can be divided into two categories according to the mode of action of the compound used: transient pharmacological impairment of dopaminergic transmission along the nigrostriatal pathway or selective destruction by a neurotoxic agent of the dopaminergic neurons of the substantia nigra pars compacta. The present article looks at the relative merits of each model, the clinical symptoms and neuronal impairment it induces, and the contribution it could make to the development of a truly dynamic model. It is becoming more and more clear that there is an urgent need for a chronic model integrating all the clinical features of PD including resting tremor, and reproducing the gradual but continuous nigral degeneration observed in the human pathology. Discrepancies have been reported several times between results obtained in classic animal models and those described in PD, and it would seem probable that such contradictions can be ascribed to the fact that animal models do not, as yet, reproduce the continuous evolution of the human disease. Dynamic experimental models which come closer to the progressive neurodegeneration and gradual intensification of motor disability so characteristic of human PD will enable us to investigate crucial aspects of the disease, such as compensatory mechanisms and dyskinesia.

Animals↗

PubMed1998

Endovascular therapy of idiopathic cavernous aneurysms over 11 years.

PURPOSE: We report our experience with 42 patients with 48 cavernous carotid aneurysms, of whom 32 were treated with endovascular techniques and 10 were managed conservatively. METHODS: The 48 aneurysms were divided into two subgroups by location: 23 were at the C-3 portion of the carotid artery (small, saccular aneurysms with an epidural, partly intracavernous location) and 25 originated at the C4-5 segment (large or giant often fusiform aneurysms with a true intracavernous location). Morphologic features in both groups correlated well with differences in clinical presentation and also influenced therapy. Sixteen of the 25 C4-5 aneurysms (all large or giant) were treated by balloon occlusion of the parent artery, four (with narrow necks) were treated with Guglielmi detachable coils (GDCs), and five were not treated (asymptomatic or minimally symptomatic). Twelve of 13 C-3 aneurysms were treated with GDCs. Ten C-3 aneurysms were not treated. RESULTS: Ophthalmoplegia resolved or improved in nine of 12 patients treated with parent artery occlusion. All aneurysms treated by carotid occlusion thrombosed. Twelve of the 17 aneurysms treated with GDCs were 100% filled by the coils, four were 80% to 95% filled, and one was only 40% filled. Seven of the 100% filled aneurysms remained completely occluded, two showed slight coil compaction, and in three, follow-up angiography was not available. Among the incompletely filled aneurysms, two remained unchanged, one showed progressive thrombosis, a fourth revealed coil compaction, and in one, follow-up angiography was not available. One thromboembolic stroke and three transient ischemic attacks occurred perioperatively, for a permanent morbidity of 3.5% and a transient morbidity of 9%. There was no mortality. Mean clinical follow-up was 33 months; mean angiographic follow-up of patients treated with GDCs was 11 months. CONCLUSION: Surgically difficult cavernous aneurysms can be obliterated by embolization with excellent clinical results. Detachable coils have become an important endovascular tool, especially for narrow-necked cavernous aneurysms of the C-3 segment, which can be protected against rupture in the subarachnoid space in most cases.

Adult↗

PubMed1997

Kinetics of nigral degeneration in a chronic model of MPTP-treated mice.

The chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model we have developed in monkey reproduces all the cardinal features of Parkinson's disease, and, in particular the characteristic slow evolution of clinical signs. We still know little, however, of the kinetics of the nigral degeneration induced. This present study charts the progressive destruction of tyrosine hydroxylase-immunoreactive neurones in mice treated daily with low doses of MPTP for 20 days. Our results show that the neuronal death rate is initially high, subsequently decreases, and stabilizes. This new protocol thus mirrors closely the pattern of evolution assumed to be that of Parkinson's disease and should prove useful for studies on neuroprotection and compensatory mechanisms.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗