Virginie Desestret | UCBL Lyon 1 (original) (raw)
Papers by Virginie Desestret
Background and Purpose-A growing body of evidence suggests that inflammatory processes are involv... more Background and Purpose-A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice.
Journal of Neuro-Ophthalmology, 2013
A 73-year-old woman was evaluated in our neuroophthalmology clinic with a 1-year history of progr... more A 73-year-old woman was evaluated in our neuroophthalmology clinic with a 1-year history of progressive difficulty reading. The patient's visual acuity, pupillary reactions to light and near stimulation, visual fields, and fundi were normal. Examination of her eye movements revealed a supranuclear vertical gaze abnormality, characterized by lack of upward saccades but intact downward saccades. The patient also had had difficulty initiating voluntary, especially leftward horizontal saccades on command, but reactive horizontal saccades were relatively well preserved. She was able to follow a pencil light moved by the examiner using small saccades (saccadic smooth pursuit) and her vestibulo-ocular reflex (VOR) was intact. She had apraxia of lid closure. The patient had no cognitive deficit, behavioral or social disturbance, aphasia, alexia, limb apraxia, postural ataxia, pyramidal signs or parkinsonism. Neuropsychological testing was hindered by reading difficulties but disclosed mild attentional and executive deficits,
Journal of Infection, 2014
Background: For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies dir... more Background: For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies directed against different synaptic proteins or receptors in patients with autoimmune encephalitis have recently been described and could indicate a differential diagnosis of infectious encephalitis. Objective: The aim of this study was to retrospectively investigate the presence of autoantibodies directed against synaptic proteins or receptors in patients with acute febrile encephalitis. Samples were collected in France in 2007 during a national prospective study. Methods: A total of 253 patients with acute febrile encephalitis were enrolled in 2007. Clinical data were collected with a standardized questionnaire. When possible, cerebrospinal fluid CSF
BMC Cancer, 2013
Background The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothel... more Background The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. Methods We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. Results In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between th...
La Revue de Médecine Interne, 2006
![Research paper thumbnail of [Near a biological diagnosis of Alzheimer's disease and related disorders]](https://attachments.academia-assets.com/94919418/thumbnails/1.jpg)
](La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne, 2008
To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and re... more To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and related disorders. As new therapeutics specific of AD may be available soon, early diagnosis of AD in the context of mild cognitive impairment (MCI) or dementia appears to be challenging. The high amount of atypical clinical forms of AD leads to develop new tools allowing in vivo diagnosis. New CerebroSpinal Fluid (CSF) biomarkers seem to reflect specific aspects of deep neuropathological changes observed in AD, i.e. amyloid deposits and neurofibrillary tangles. Amyloid beta-peptide 1-42 (Abeta(1-42)) and hyperphosphorylated tubulin associated unit (tau) isoforms appear to be the most sensitive and specific CSF biomarkers, the combination of these biomarkers depicting the best diagnosis value for AD. These molecules are also efficient in the prediction of the conversion from the MCI state to the dementia state of AD. Combined to clinical and neuro-imaging information, CSF biomarkers appear...
Brain : a journal of neurology, 2015
later after patients have been seizurefree for extended periods of time (Simasathien et al., 2013... more later after patients have been seizurefree for extended periods of time (Simasathien et al., 2013). The complexity of the findings, as well as the implications for planning resection in younger brains, are considerable. While all brains are capable of plasticity to some degree, we generally think of the greatest potential for plasticity as being in the first few years of life, with plasticity dropping off steeply in adolescence and early adulthood. Given that the average age at surgery was 13, this raises questions about whether the findings might have implications for older surgical patients, many of whom also have epilepsy of early childhood onset. Perhaps most importantly, the findings of Skirrow and colleagues highlight the urgent need for earlier intervention and the importance of considering developmental plasticity and reorganization as part of efforts to spare and maximize post-surgical cognitive function.
Journal of Alzheimer's disease : JAD, 2014
Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a ... more Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown. The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD. Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Thre...
BioMed research international, 2014
IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these ... more IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated--which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation ...
Journal of neurology, neurosurgery, and psychiatry, Jan 4, 2014
Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a... more Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a large (>650) hexanucleotide GGCCTG repeat expansion in the first intron of the NOP56 gene. The aim of this study is to clarify the prevalence, clinical and genetic features of SCA36. The expansion was tested in 676 unrelated SCA index cases and 727 controls from France, Germany and Japan. Clinical and neuropathological features were investigated in available family members. Normal alleles ranged between 5 and 14 hexanucleotide repeats. Expansions were detected in 12 families in France (prevalence: 1.9% of all French SCAs) including one family each with Spanish, Portuguese or Chinese ancestry, in five families in Japan (1.5% of all Japanese SCAs), but were absent in German patients. All the 17 SCA36 families shared one common haplotype for a 7.5 kb pairs region flanking the expansion. While 27 individuals had typically long expansions, three affected individuals harboured small hexanu...
PloS one, 2013
THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident... more THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1) and alternatively activated (M2) macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle) were intravenously administered during the subacute stage of ischemia (D4) in a model of tran...
Background and Purpose-A growing body of evidence suggests that inflammatory processes are involv... more Background and Purpose-A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice. Methods-Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours. Results-We here present the first MRI data showing in vivo phagocyte-labeling obtained in mice with focal cerebral ischemia. USPIO-enhanced MRI kinetic analysis disclosed an inflammatory response surrounding the ischemic lesion and in the contralateral hemisphere via the corpus callosum. The imaging data collected during the first 36 hours postinjury suggested a spread of USPIO-related signal from ipsi-to contralateral hemisphere. Imaging data correlated with histochemical analysis showing inflammation remote from the lesion and ingestion of nanoparticles by microglia/macrophages. Conclusions-The present study shows that MR-tracking of phagocyte cells is feasible in mice, which may have critical therapeutic implications given the potential neurotoxicity of activated microglia/macrophages in central nervous system disorders. (Stroke. 2007;38:000-000.)
Stroke, 2007
We are grateful to Bendszus et al for their letter because their comments further improve the dis... more We are grateful to Bendszus et al for their letter because their comments further improve the discussion of our article, 1 raising important questions about the interpretation of MR signal loss at the early stage of focal cerebral ischemia. The authors indeed suggest that in this context the hypointense rim surrounding the ischemic lesion might be related to ongoing thrombus formation.
Stroke, 2009
Background and Purpose— MR signal changes after intravenous ultrasmall superparamagnetic iron oxi... more Background and Purpose— MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke. Methods— Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood–brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture. Results—...
Stroke, 2009
Background and Purpose— The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mis... more Background and Purpose— The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch may identify patients who benefit from thrombolysis. However, some patients exhibit a “total mismatch,” ie, negative DWI but extensive PWI defect. We aimed to assess clinical and MRI data of these patients. Methods— From June 2007 to December 2008, patients with anterior circulation ischemic stroke were evaluated for a “total mismatch” profile. MRI was performed at admission and at day 1. The score was assessed at baseline and the modified Rankin scale score was assessed at day 30. Results— Among 52 patients, 3 showed a total mismatch with arterial occlusion confirmed on magnetic resonance angiography. All had fluctuating symptoms (National Institutes of Health Stroke Scale scores, 0 to 10) and received intravenous tissue plasminogen activator. Day 1 DWI disclosed minimal changes in all patients. Outcome was favorable in all patients (day 30 modified Rankin scale, 0–1). Conclusion—...
Neuro-Oncology, 2012
Background. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs... more Background. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at 7 loci influencing glioma risk: rs2736100 (TERT), rs11979158 and rs2252586 (EGFR), rs4295627 (CCDC26), rs4977756 (CDKN2A/CDKN2B), rs498872 (PHLDB1), and rs6010620 (RTEL1). Materials and methods. We studied the relationship among these 7 glioma-risk SNPs and characteristics of tumors from 1374 patients, including grade, IDH (ie IDH1 or IDH2) mutation, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, 9p and 10q loss, and 1p-19q codeletion. Results. rs2736100 (TERT) and rs6010620 (RTEL1) risk alleles were associated with high-grade disease, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, and 9p and 10q deletion; rs4295627 (CCDC26) and rs498872 (PHLDB1) were associated with low-grade disease, IDH mutation, and 1p-19q codeletion. In contrast, rs4977756 (CDKN2A/B), rs11979158 (EGFR), and to a lesser extent, rs2252586 (EGFR) risk alleles were independent of tumor grade and genetic profile. Adjusting for tumor grade showed a significant association between rs2736100 and IDH status (P ¼ .01), 10q loss (P ¼ .02); rs4295627 and 1p-19q codeletion (P ¼ .04), rs498872 and IDH (P ¼ .02), 9p loss (P ¼ .04), and 10q loss (P ¼ .02). Case-control analyses stratified into 4 molecular classes (defined by 1p-19q status, IDH mutation, and EGFR amplification) showed an association of rs4295627 and rs498872 with IDH-mutated gliomas (P , 10 23) and rs2736100 and rs6010620 with IDH wild-type gliomas (P , 10 23 and P ¼ .03). Conclusion. The frequency of EGFR and CDKN2A/B risk alleles were largely independent of tumor genetic profile, whereas TERT, RTEL1, CCDC26, and PHLDB1 variants were associated with different genetic profiles that annotate distinct molecular pathways. Our findings provide further insight into the biological basis of glioma etiology.
Background and Purpose-A growing body of evidence suggests that inflammatory processes are involv... more Background and Purpose-A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice.
Journal of Neuro-Ophthalmology, 2013
A 73-year-old woman was evaluated in our neuroophthalmology clinic with a 1-year history of progr... more A 73-year-old woman was evaluated in our neuroophthalmology clinic with a 1-year history of progressive difficulty reading. The patient's visual acuity, pupillary reactions to light and near stimulation, visual fields, and fundi were normal. Examination of her eye movements revealed a supranuclear vertical gaze abnormality, characterized by lack of upward saccades but intact downward saccades. The patient also had had difficulty initiating voluntary, especially leftward horizontal saccades on command, but reactive horizontal saccades were relatively well preserved. She was able to follow a pencil light moved by the examiner using small saccades (saccadic smooth pursuit) and her vestibulo-ocular reflex (VOR) was intact. She had apraxia of lid closure. The patient had no cognitive deficit, behavioral or social disturbance, aphasia, alexia, limb apraxia, postural ataxia, pyramidal signs or parkinsonism. Neuropsychological testing was hindered by reading difficulties but disclosed mild attentional and executive deficits,
Journal of Infection, 2014
Background: For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies dir... more Background: For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies directed against different synaptic proteins or receptors in patients with autoimmune encephalitis have recently been described and could indicate a differential diagnosis of infectious encephalitis. Objective: The aim of this study was to retrospectively investigate the presence of autoantibodies directed against synaptic proteins or receptors in patients with acute febrile encephalitis. Samples were collected in France in 2007 during a national prospective study. Methods: A total of 253 patients with acute febrile encephalitis were enrolled in 2007. Clinical data were collected with a standardized questionnaire. When possible, cerebrospinal fluid CSF
BMC Cancer, 2013
Background The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothel... more Background The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. Methods We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. Results In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between th...
La Revue de Médecine Interne, 2006
La Revue de médecine interne / fondée ... par la Société nationale francaise de médecine interne, 2008
To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and re... more To review the current concepts in the biological diagnosis of Alzheimer's disease (AD) and related disorders. As new therapeutics specific of AD may be available soon, early diagnosis of AD in the context of mild cognitive impairment (MCI) or dementia appears to be challenging. The high amount of atypical clinical forms of AD leads to develop new tools allowing in vivo diagnosis. New CerebroSpinal Fluid (CSF) biomarkers seem to reflect specific aspects of deep neuropathological changes observed in AD, i.e. amyloid deposits and neurofibrillary tangles. Amyloid beta-peptide 1-42 (Abeta(1-42)) and hyperphosphorylated tubulin associated unit (tau) isoforms appear to be the most sensitive and specific CSF biomarkers, the combination of these biomarkers depicting the best diagnosis value for AD. These molecules are also efficient in the prediction of the conversion from the MCI state to the dementia state of AD. Combined to clinical and neuro-imaging information, CSF biomarkers appear...
Brain : a journal of neurology, 2015
later after patients have been seizurefree for extended periods of time (Simasathien et al., 2013... more later after patients have been seizurefree for extended periods of time (Simasathien et al., 2013). The complexity of the findings, as well as the implications for planning resection in younger brains, are considerable. While all brains are capable of plasticity to some degree, we generally think of the greatest potential for plasticity as being in the first few years of life, with plasticity dropping off steeply in adolescence and early adulthood. Given that the average age at surgery was 13, this raises questions about whether the findings might have implications for older surgical patients, many of whom also have epilepsy of early childhood onset. Perhaps most importantly, the findings of Skirrow and colleagues highlight the urgent need for earlier intervention and the importance of considering developmental plasticity and reorganization as part of efforts to spare and maximize post-surgical cognitive function.
Journal of Alzheimer's disease : JAD, 2014
Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a ... more Alzheimer's disease (AD) clinical onset is usually characterized by a memory complaint and a progressive memory deficit. The proportion of typical medial-temporal amnesia revealing AD remains unknown. The present study explores the episodic memory impairment profiles by the Free and Cued Selective Recall Reminding Test (FCSRT) in patients with initial memory complaint and a cerebrospinal fluid (CSF) biomarker signature of AD. Seventy-three patients referred for memory complaint to the Centers for Memory, Resource and Research of Lyon and Montpellier (France) were included consecutively. All patients underwent an extensive neuropsychological examination and had a Mini-Mental State Examination (MMSE) score ≥20 and a positive CSF AD signature. The patients were classified as having mild dementia or prodromal AD. Verbal episodic memory was assessed using the French version of the FCSRT exploring encoding, storage/consolidation, and cued delayed retrieval phases of memorization. Thre...
BioMed research international, 2014
IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these ... more IDH1/2 mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed that IDH mutation is almost constant in 1p19q codeleted tumors. We found that the distribution of IDH1(R132H) , IDH1(nonR132H) , and IDH2 mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation of IDH2 mutations in oligodendroglial phenotype and an overrepresentation of IDH1(nonR132H) in astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q and IDH mutation to define three distinct prognostic subgroups: 1p19q and IDH mutated, IDH mutated--which contains mostly TP53 mutated tumors, and none of these alterations. We confirmed that IDH mutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge on IDH mutation ...
Journal of neurology, neurosurgery, and psychiatry, Jan 4, 2014
Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a... more Spinocerebellar ataxia 36 (SCA36) is an autosomal-dominant neurodegenerative disorder caused by a large (>650) hexanucleotide GGCCTG repeat expansion in the first intron of the NOP56 gene. The aim of this study is to clarify the prevalence, clinical and genetic features of SCA36. The expansion was tested in 676 unrelated SCA index cases and 727 controls from France, Germany and Japan. Clinical and neuropathological features were investigated in available family members. Normal alleles ranged between 5 and 14 hexanucleotide repeats. Expansions were detected in 12 families in France (prevalence: 1.9% of all French SCAs) including one family each with Spanish, Portuguese or Chinese ancestry, in five families in Japan (1.5% of all Japanese SCAs), but were absent in German patients. All the 17 SCA36 families shared one common haplotype for a 7.5 kb pairs region flanking the expansion. While 27 individuals had typically long expansions, three affected individuals harboured small hexanu...
PloS one, 2013
THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident... more THE INFLAMMATORY RESPONSE FOLLOWING ISCHEMIC STROKE IS DOMINATED BY INNATE IMMUNE CELLS: resident microglia and blood-derived macrophages. The ambivalent role of these cells in stroke outcome might be explained in part by the acquisition of distinct functional phenotypes: classically (M1) and alternatively activated (M2) macrophages. To shed light on the crosstalk between hypoxic neurons and macrophages, an in vitro model was set up in which bone marrow-derived macrophages were co-cultured with hippocampal slices subjected to oxygen and glucose deprivation. The results showed that macrophages provided potent protection against neuron cell loss through a paracrine mechanism, and that they expressed M2-type alternative polarization. These findings raised the possibility of using bone marrow-derived M2 macrophages in cellular therapy for stroke. Therefore, 2 million M2 macrophages (or vehicle) were intravenously administered during the subacute stage of ischemia (D4) in a model of tran...
Background and Purpose-A growing body of evidence suggests that inflammatory processes are involv... more Background and Purpose-A growing body of evidence suggests that inflammatory processes are involved in the pathophysiology of stroke. Phagocyte cells, involving resident microglia and infiltrating macrophages, secrete both protective and toxic molecules and thus represent a potential therapeutic target. The aim of the present study was to monitor phagocytic activity after focal cerebral ischemia in mice. Methods-Ultrasmall superparamagnetic particles of iron oxide (USPIO) were intravenously injected after permanent middle cerebral artery occlusion and monitored by high resolution MRI for 72 hours. Results-We here present the first MRI data showing in vivo phagocyte-labeling obtained in mice with focal cerebral ischemia. USPIO-enhanced MRI kinetic analysis disclosed an inflammatory response surrounding the ischemic lesion and in the contralateral hemisphere via the corpus callosum. The imaging data collected during the first 36 hours postinjury suggested a spread of USPIO-related signal from ipsi-to contralateral hemisphere. Imaging data correlated with histochemical analysis showing inflammation remote from the lesion and ingestion of nanoparticles by microglia/macrophages. Conclusions-The present study shows that MR-tracking of phagocyte cells is feasible in mice, which may have critical therapeutic implications given the potential neurotoxicity of activated microglia/macrophages in central nervous system disorders. (Stroke. 2007;38:000-000.)
Stroke, 2007
We are grateful to Bendszus et al for their letter because their comments further improve the dis... more We are grateful to Bendszus et al for their letter because their comments further improve the discussion of our article, 1 raising important questions about the interpretation of MR signal loss at the early stage of focal cerebral ischemia. The authors indeed suggest that in this context the hypointense rim surrounding the ischemic lesion might be related to ongoing thrombus formation.
Stroke, 2009
Background and Purpose— MR signal changes after intravenous ultrasmall superparamagnetic iron oxi... more Background and Purpose— MR signal changes after intravenous ultrasmall superparamagnetic iron oxide (USPIO) injection are related to inflammatory cells at the subacute stages after focal cerebral injury. However, at the early stages, the interpretation of USPIO-related MR signal alterations remains controversial. Here, we compared MR signal changes after intravenous USPIO injection with the histological iron and macrophage distribution during the first 24 hours in a rodent model of acute stroke. Methods— Multiparametric MRI at 7T and histological USPIO distribution were confronted from 6 to 24 hours after permanent middle cerebral artery occlusion in mice. Blood–brain barrier disruption was assessed using gadolinium MRI and immunoglobulin staining. Prussian blue staining was performed to depict the USPIO brain distribution. USPIO uptake by phagocytes was assessed by immunochemistry on brain tissue, peripheral blood cells, and monocyte cells derived from bone marrow culture. Results—...
Stroke, 2009
Background and Purpose— The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mis... more Background and Purpose— The perfusion-weighted imaging (PWI)/diffusion-weighted imaging (DWI) mismatch may identify patients who benefit from thrombolysis. However, some patients exhibit a “total mismatch,” ie, negative DWI but extensive PWI defect. We aimed to assess clinical and MRI data of these patients. Methods— From June 2007 to December 2008, patients with anterior circulation ischemic stroke were evaluated for a “total mismatch” profile. MRI was performed at admission and at day 1. The score was assessed at baseline and the modified Rankin scale score was assessed at day 30. Results— Among 52 patients, 3 showed a total mismatch with arterial occlusion confirmed on magnetic resonance angiography. All had fluctuating symptoms (National Institutes of Health Stroke Scale scores, 0 to 10) and received intravenous tissue plasminogen activator. Day 1 DWI disclosed minimal changes in all patients. Outcome was favorable in all patients (day 30 modified Rankin scale, 0–1). Conclusion—...
Neuro-Oncology, 2012
Background. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs... more Background. Genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at 7 loci influencing glioma risk: rs2736100 (TERT), rs11979158 and rs2252586 (EGFR), rs4295627 (CCDC26), rs4977756 (CDKN2A/CDKN2B), rs498872 (PHLDB1), and rs6010620 (RTEL1). Materials and methods. We studied the relationship among these 7 glioma-risk SNPs and characteristics of tumors from 1374 patients, including grade, IDH (ie IDH1 or IDH2) mutation, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, 9p and 10q loss, and 1p-19q codeletion. Results. rs2736100 (TERT) and rs6010620 (RTEL1) risk alleles were associated with high-grade disease, EGFR amplification, CDKN2A-p16-INK4a homozygous deletion, and 9p and 10q deletion; rs4295627 (CCDC26) and rs498872 (PHLDB1) were associated with low-grade disease, IDH mutation, and 1p-19q codeletion. In contrast, rs4977756 (CDKN2A/B), rs11979158 (EGFR), and to a lesser extent, rs2252586 (EGFR) risk alleles were independent of tumor grade and genetic profile. Adjusting for tumor grade showed a significant association between rs2736100 and IDH status (P ¼ .01), 10q loss (P ¼ .02); rs4295627 and 1p-19q codeletion (P ¼ .04), rs498872 and IDH (P ¼ .02), 9p loss (P ¼ .04), and 10q loss (P ¼ .02). Case-control analyses stratified into 4 molecular classes (defined by 1p-19q status, IDH mutation, and EGFR amplification) showed an association of rs4295627 and rs498872 with IDH-mutated gliomas (P , 10 23) and rs2736100 and rs6010620 with IDH wild-type gliomas (P , 10 23 and P ¼ .03). Conclusion. The frequency of EGFR and CDKN2A/B risk alleles were largely independent of tumor genetic profile, whereas TERT, RTEL1, CCDC26, and PHLDB1 variants were associated with different genetic profiles that annotate distinct molecular pathways. Our findings provide further insight into the biological basis of glioma etiology.