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P Garnier

Publications and source records attributed to P Garnier.

At least 19 recordsLinked to original sources
PubMed2006

Effect of early decrease in the lesion size on late brain tissue loss, synaptophysin expression and functionality after a focal brain lesion in rats.

The purpose of the present study is to determine the effects of early decrease in the lesion size on late brain tissue loss, synaptogenesis and functionality after a focal brain lesion in rats. The lesion was induced either to the cortex using the photothrombotic ischemic stroke or to the striatum using the malonate poisoning model. The cortical and striatal lesions amounted to 66-80 mm(3) at day 1 post-lesion and were reduced by 50% after the acute administration of dipyridyl (a liposoluble iron chelator) and aminoguanidine (an inhibitor of the inducible nitric oxide synthase), respectively. Loss of histologically intact tissue and synaptophysin expression as an indicator of synaptogenesis were examined at day 35 post-lesion. Both types of lesion resulted in synaptophysin upregulation in contralateral and ipsilateral cortical areas. On the contrary, brain tissue loss was greater after the striatal (-17%) than the cortical lesion (-5%). Synaptophysin expression and tissue loss were not different between drug- and vehicle-treated rats. Moreover, a set of standard neurological tests revealed a difference in deficit between the both types of lesion, yet only in the acute post-lesion stage. However, it did not distinguish between vehicle- and drug-treated rats whatever the lesion location. Our results indicate that late histological endpoints measurements are not recommended to probe the potential neuroprotective properties of a drug administered within the acute post-lesion stage. They also suggest that inhibition of cytotoxic mechanisms involved in lesion growth is of no clinical interest when it cannot lead to a long-term histological protection and/or increased synaptogenesis.

2,2'-Dipyridyl↗
PubMed2006

Prevalence of low HDL-cholesterol in patients with cardiovascular risk factors: The ECHOS (Etude du Cholesterol HDL en Observationnel) French Survey.

A low concentration of high-density lipoprotein-cholesterol (HDL-C) is an independent risk factor for cardiovascular heart disease (CHD), but little is known about the distribution of HDL-C in France. This study evaluated the prevalence of low HDL-C among a large French population (5232 patients) with other cardiovascular risk factors. Depending on the guidelines used, the prevalence of low HDL-C varied from 8.7% (cutoff value of 35 mg/dl) to 26.9% (National Cholesterol Education Program metabolic syndrome cutoff values). The prevalence of low HDL-C gradually increased with the number of associated risk factors. We identified three independent risk predictors for low HDL-C: hypertriglyceridaemia (HTG), abdominal obesity and gender. Overall, the frequency of HDL-C assessment was very high (>85%) and it was highest in patients with hypercholesterolaemia or a history of CHD. Risk factors more frequently associated with low HDL-C (i.e. HTG, abdominal obesity and type 2 diabetes) were not associated with a more frequent assessment of HDL-C. Our findings indicate that in France, the prevalence of low HDL-C remains relatively high, particularly for patients with obesity and HTG.

Body Mass Index↗
PubMed2004

[Intracranial extension of extracranial vertebral artery dissections. A review of 16 cases].

INTRODUCTION: Vertebral artery (VA) dissections can involve both the extracranial and intracranial portions of the VA. Intradural extension explains the occurrence of subarachnoid hemorrage (SAH). We have studied the rate of this extension, the risk of associated SAH and the therapeutic repercussions at the acute stage. METHODS: From 1985 to 2001, 42 patients with a recent extracranial VA dissection were admitted to our department of neurology. When the diagnosis of extracranial VA dissection (involving the first, second or third segment of the VA) was established, we looked for an ipsilateral intracranial extension (involving the fourth segment of the VA and/or the basilar artery). VA dissections strictly located at the intracranial level were excluded. RESULTS: Among 42 patients with angiographically diagnosed extracranial VA dissections, 16 patients (38 percent) had an ipsilateral intradural extension. Two of them developed an inaugural and spontaneous SAH. After a mean follow-up of 4 Months under antithrombotic treatment, none of the patients has developed SAH or recurrent SAH. CONCLUSIONS: Because of the potential risk for spontaneous SAH at the acute stage, it seems important to exclude an intracranial extension. Lumbar puncture should be undertaken to exclude SAH before consideration of antithrombotic therapy.

Adult↗
PubMed2003

Effects of a direct injection of liposoluble iron into rat striatum. Importance of the rate of iron delivery to cells.

For a better understanding of the role of iron imbalance in neuropathology, a liposoluble iron complex (ferric hydroxyquinoline, FHQ) was injected into striatum of rats. The effects of two modalities of iron injections on brain damage, hydroxyl radical (*OH) production (assessed by the salicylate method coupled to microdialysis) and tissue reactive iron level (evaluated ex vivo by the propensity of the injected structure for lipid peroxidation) were examined. Rapid injection of FHQ (10 nmoles of 5 mM FHQ pH 3 solution over 1-min period) but not that of corresponding vehicle led to extensive damage associated with increased tissue free iron level in the injected region. Conversely, neither lesion nor free iron accumulation was observed after slow FHQ injection (10 nmoles of a 100 microM FHQ pH 7 solution over 1-h period) as compared to corresponding vehicle injection. Production of *OH was induced by slow FHQ injection but not by rapid FHQ injection, probably as a result of in vivo abolition of iron-induced *OH formation by acid pH. Indeed, rapid injection of FAC pH 7 (ferric ammonium citrate, 5 mM in saline) was associated with *OH formation whereas rapid injection of FAC pH 3 did not. Our results identify the rate of iron delivery to cells as an important determinant of iron toxicity and do not support a major role for extracellular *OH in damage associated with intracerebral iron injection.

Animals↗
PubMed2003

Effects of iNOS-related NO on hearts exposed to liposoluble iron.

Inducible nitric oxide synthase (iNOS) protects heart against ischemia/reperfusion injury. However, it is unknown whether the beneficial effects of iNOS are mediated by the interaction of NO with radical oxygen species (ROS). To address this issue, we examined the effects of liposoluble iron-induced ROS generation in isolated perfused hearts from rats treated with lipopolysaccharide (LPS). LPS administration (10 mg/kg, i.p., 6 h before heart removal) induced iNOS expression and increased NO production as indicated by a 3-fold elevation of nitrite level in coronary effluents relative to control hearts. An enhanced expression of hemeoxygenase 1 protein was also observed in septic hearts compared to control. Iron-induced perfusion and contractile deficits were ameliorated by LPS with more important coronary than myocardial benefits. In iron-loaded hearts, oxidative stress as measured by the 2,3 dihydroxybenzoic acid/salicylic acid concentration ratio in cardiac tissue was 23% lower in septic than in control heart although the difference did not reach significance. In addition, the presence of the NO synthase inhibitor N-nitro-L-arginine in the perfusion medium totally blocked NO production but did not reverse the protective effects of LPS. The results indicate that LPS protects from iron-induced cardiac dysfunction by mechanisms independent on ex vivo NO production and suggest that NO acts as a trigger rather than a direct mediator of the cardioprotective effects of LPS in heart exposed to iron.

Animals↗
PubMed2003

[Cerebral angiitis and Goodpasture's syndrome].

Goodpasture's syndrome is a form of rapidly progressive glomerulonephritis with pulmonary hemorrhage in the presence of antiglomerular basement membrane antibodies. Concomittant central nervous system manifestations are exceptionally reported. We report such a case of an 55-year-old woman who developed fluctuant neurobehavioral manifestations over a 9 months period. Angiography showed cerebral arterial distal lesions compatible with the diagnosis of angiitis. The antiglomerular basement membrane antibody titer was elevated. Search for anti-neutrophil cytoplasmic antibody was negative. After the reintroduction of cyclophosphamide agent, clinical evolution was favourable. Clinical cerebral manifestations in our case are probably du to a angiitis. Few cases are reported in the literature. The role of antiglomerular basement membrane antibody in the development of the cerebral angiitis is possible.

Anti-Glomerular Basement Membrane Disease↗
PubMed2002

Chemical preconditioning with 3-nitropropionic acid: lack of induction of neuronal tolerance in gerbil hippocampus subjected to transient forebrain ischemia.

Chemical preconditioning using the mitochondrial toxin, 3-nitropropionic acid (3-NP) has been reported to induce neuroprotection against subsequent global ischemia. To investigate the underlying mechanisms, Mongolian gerbils were pretreated with either vehicle or 3-NP at the dose of 3 or 10 mg/kg, intraperitoneal, 3 days prior to a 5-min bilateral carotid artery occlusion followed by either 48 h or 7 days of blood recirculation. Neuronal damage was assessed by a cresyl violet/fuchsin acid staining. Induction of heat shock protein 72 (HSP72) and manganese superoxide dismutase (MnSOD) expression was evaluated by Western blotting. Astroglial and microglial activation was detected by immunohistochemistry (glial fibrillary acid protein) and by histochemistry (isolectin B4 staining), respectively. Present data show that the hippocampal neuronal damage induced by ischemia were of similar extent between the vehicle- and 3-NP-treated gerbils, whatever the dose tested, indicating that 3-NP did not induce tolerance to transient forebrain ischemia under our experimental conditions. The lack of difference in the post-ischemic level of HSP72 and MnSOD protein expression and in the intensity of astroglial and microglial activation represents further indirect indications of the absence of 3-NP preconditioning effect. In conclusion, although chemical preconditioning with 3-NP is a well-established phenomenon at least in vitro and in models of focal ischemia, the relevance of 3-NP as a preconditioning molecule towards global brain ischemia remains an open question.

Adaptation, Physiological↗
PubMed2001

Structural and functional analysis of the RANTES-glycosaminoglycans interactions.

Chemokines mediate their biological activity through activation of G protein coupled receptors, but most chemokines, including RANTES, are also able to bind glycosaminoglycans (GAGs). Here, we have investigated, by site-directed mutagenesis and chemical acetylation, the role of RANTES basic residues in the interaction with GAGs using surface plasmon resonance kinetic analysis. Our results indicate that (i) RANTES exhibited selectivity in GAGs binding with highest affinity (K(d) = 32.1 nM) for heparin, (ii) RANTES uses the side chains of residues R44, K45, and R47 for heparin binding, and blocking these residues in combination abolished heparin binding. The biological relevance of RANTES-GAGs interaction was investigated in CHO-K1 cells expressing CCR5, CCR1, or CCR3 and the various GAGs that bind RANTES. Our results indicate that the heparin binding site, defined as the 40s loop, is only marginally involved in CCR5 binding and activation, but largely overlaps the CCR1 and CCR3 binding and activation domain in RANTES. In addition, enzymatic removal of cell surface GAGs by glycosidases did not affect CCR5 binding and Ca(2+) response. Furthermore, addition of soluble GAGs inhibited both CCR5 binding and functional response, with a rank of potency similar to that found in surface plasmon resonance experiments. Thus, cell surface GAGs is not a prerequisite for receptor binding or signaling, but soluble GAGs can inhibit the binding and the functional response of RANTES to CCR5 expressing cells. However, the marked selectivity of RANTES for different GAGs may serve, in vivo, to control the concentration of specific chemokines in inflammatory situations and locations.

Acetylation↗
PubMed2001

Stress response to hypoxia in gerbil brain: HO-1 and Mn SOD expression and glial activation.

Hypoxic preconditioning has been shown to induce neuroprotection against a subsequent damaging insult. In order to study the underlying molecular and cellular mechanisms of hypoxic preconditioning, we investigated, in gerbil hippocampus, the effects in vivo of transient exposure to hypoxia (4% O(2) for 6 min followed by either 48 h or 7 days of reoxygenation) (i) on the induction of 72 kDa heat shock protein (HSP72), heme oxygenase-1 (HO-1) and manganese superoxide dismutase (Mn SOD) as assessed by Western immunoblotting and (ii) on the astroglial and microglial activation as detected by both immunohistochemistry and Western immunoblotting for GFAP, and histochemistry for isolectin B4, respectively. Our data show that, although hypoxia and subsequent reoxygenation led to neither neuronal damage nor HSP72 induction in gerbil hippocampus, it induced a progressive and sustained expression of HO-1 and Mn SOD. As expected from the absence of neuronal death, hypoxia was not associated with microglial activation but led to a significant astrocytic activation. These findings demonstrate that transient hypoxia enhances the antioxidative enzymatic defenses of the brain, which are susceptible to increased tolerance against a subsequent damaging insult.

Animals↗
PubMed2001

N-Acetylaspartate, a marker of both cellular dysfunction and neuronal loss: its relevance to studies of acute brain injury.

To evaluate the contribution of cellular dysfunction and neuronal loss to brain N-acetylaspartate (NAA) depletion, NAA was measured in brain tissue by HPLC and UV detection in rats subjected to cerebral injury, associated or not with cell death. When lesion was induced by intracarotid injection of microspheres, the fall in NAA was related to the degree of embolization and to the severity of brain oedema. When striatal lesion was induced by local injection of malonate, the larger the lesion volume, the higher the NAA depletion. However, reduction of brain oedema and striatal lesion by treatment with the lipophilic iron chelator dipyridyl (20 mg/kg, 1 h before and every 8 h after embolization) and the inducible nitric oxide synthase inhibitor aminoguanidine (100 mg/kg given 1 h before malonate and then every 9 h), respectively, failed to ameliorate the fall in NAA. Moreover, after systemic administration of 3-nitropropionic acid, a marked reversible fall in NAA striatal content was observed despite the lack of tissue necrosis. Overall results show that cellular dysfunction can cause higher reductions in NAA level than neuronal loss, thus making of NAA quantification a potential tool for visualizing the penumbra area in stroke patients.

2,2'-Dipyridyl↗
PubMed2001

Effects of polyethylene glycol 4000 on 24-h manometric recordings of left colonic motor activity.

BACKGROUND: It has been shown that low doses of polyethylene glycol (PEG) 4000 are effective in the treatment of chronic constipation. The aim of this study was to describe the effects on colonic motility of oral PEG 4000 treatment and intraluminal instillation of PEG 4000. METHODS: Left colonic and rectosigmoid manometric recordings were performed for 27 h in six constipated patients and in six healthy volunteers. At the end of the recording, bisacodyl and PEG 4000 were instilled into the lumen of the colon. To assess the effects of oral administration of PEG 4000 on colonic motility, manometric recordings were also performed in constipated patients after 4 weeks of treatment with PEG 4000. RESULTS: All patients had significantly more stools during than before PEG treatment. There was no significant difference between the number and the characteristics of high-amplitude propagating contractions (HAPC) or the area under the curve (AUC) before or during treatment with PEG 4000. Intraluminal instillation of PEG induced HAPC in only one patient and in no controls. CONCLUSION: This study shows that PEG 4000 has no effect on left colonic and rectosigmoid motor activity during oral treatment, despite its clinical effectiveness, or after local instillation.

Administration, Oral↗
PubMed2000

[Roles of arterial dysplasia, chronic ergotism and other factors in a case multiple spontaneous arterial dissections].

INTRODUCTION: Spontaneous dissection of cervical and visceral arteries are rare and usually associated with an underlying arterial disease. EXEGESIS: The authors report the unusual case of a 50-year-old woman with high blood pressure who presented spontaneous dissection of cervico-cephalic, renal and hepatic arteries and of the descending aorta. She had been taking ergotamine tartrate for ten years for migraine. She also suffered from Raynaud's syndrome worsened by treatment. CONCLUSION: The respective roles of arterial dysplasia, chronic ergotism, renovascular hypertension and migraine are discussed.

Aortic Dissection↗
PubMed2000

[Two new cases of cardiac papillary fibroelastoma with ischemic stroke].

A 22 and 25 year-old man were admitted to our emergency care unit for a stroke of the left superficial middle cerebral artery territory and vertebrobasilar infarction. Complete assessment of ischemic attack retained, in both cases, the presence of a valvular cardiac tumor. After heparin treatment, surgery confirmed the data provided by echocardiography. Histology confirmed the diagnosis of a papillary fibroelastoma. The diagnosis of cardiac tumors is based on transthoracic echocardiography and transesophageal echocardiography (TEE). High definition TEE allows localizing the tumor and determining its relationship with the contiguous anatomical structures. TEE is also a better guide for surgical procedure. Echocardiography is essential in the management of cerebral ischemic attacks in young patients.

Adult↗
PubMed1999

Spinal curvatures and quality of life in women with vertebral fractures secondary to osteoporosis.

STUDY DESIGN: A prospective cross-sectional case-control study. OBJECTIVES: To compare spinal curvatures in women with osteoporosis and control subjects with a new instrument, the curviscope. SUMMARY OF BACKGROUND DATA: Few instruments are available for measuring spinal curvatures in the sagittal plane. Most of them have poor reproducibility, and they have been poorly investigated in osteoporosis. METHODS: Ninety-eight postmenopausal women were evaluated. They were divided into two groups, according to their bone status: women with osteoporosis with at least one vertebral fracture (n = 51) and control subjects (n = 47). Women with osteoporosis were divided into two subgroups, according to the delay since the last vertebral fracture had occurred (i.e., more or less than 3 months). Quality of life was assessed by using a generic instrument, the Nottingham Health Profile, in patients with osteoporosis only. RESULTS: Reproducibility of the curviscope was satisfactory. For kyphosis measurements, the coefficients of variation were 2.8% and 2.4% in control subjects and women with osteoporosis, respectively. Kyphosis values were significantly higher in women with osteoporosis than in age-matched control subjects (63 degrees +/- 13 degrees vs. 52 degrees +/- 11 degrees, respectively; P < 0.005). Nottingham Health Profile scores were significantly different (P < 0.05) in women with osteoporosis with a recently diagnosed vertebral fracture, compared with other women with osteoporosis in two aspects, physical mobility and energy. Kyphosis measurements were significantly correlated with age in the whole group (r = 0.26; P < 0.05). In the Nottingham Health Profile, physical mobility was significantly correlated with kyphosis (r = 0.35; P < 0.05). CONCLUSIONS: The curviscope is a reliable tool, particularly useful in the assessment of osteoporosis. Moreover, kyphosis angles measured with the curviscope are markedly increased in women with osteoporosis, compared with control subjects. Finally, an increase of kyphosis angles is associated with decreased physical mobility.

Aged↗
PubMed1999

Preischemic blood glucose supply to the brain modulates HSP(72) synthesis and neuronal damage in gerbils.

Preischemic hyperglycemia is known to aggravate brain damage caused by transient forebrain ischemia. Because heat shock proteins (HSPs) 72 have been proposed to play a protective role against ischemic neuronal injury, we studied the HSP(72) mRNA expression and protein synthesis in gerbils subjected to 10 min bilateral carotid occlusion under normoglycemic, hyperglycemic and fasting conditions. HSP(72) mRNA expression and HSP(72) synthesis were studied using in situ hybridization and immunostaining, respectively. After 8 h of blood recirculation, HSP(72) mRNAs were expressed in all the hippocampal subfields of the three different groups, with higher expression in the hyperglycemic gerbils. After 48 h of reperfusion, HSP(72) mRNAs had almost completely disappeared in the hyper- and normoglycemic groups, and were more strongly expressed in the CA(1) neurons of the fasted group. At this time, fasted gerbils exhibited intense HSP(72) immunoreactivity in the CA(1), whereas an absence of immunoreactivity was observed in that area in the other groups. Finally, ischemia was also associated with marked astrocytic activation, as evidenced by GFAP immunostaining. Overall results indicate that preischemic differences in blood glucose supply to the brain are related to HSP(72) mRNA expression (in terms of duration) and to HSP(72) protein induction (in terms of intensity) in the vulnerable CA(1) neurons of the hippocampus. Ability of CA(1) neurons to synthesize HSP(72) proteins was associated with higher neuronal survival in the fasted group after 48 h of reflow, suggesting a protective role of HSP(72), even though evaluation of neuronal damage at 7 days indicated that neuronal death was mainly delayed in the time.

Animals↗