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Biomedical subjects

J Poirier

Publications and source records attributed to J Poirier.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Neuropathology in France (19th-20th centuries). Semantic and institutional misadventures].

At the end of the 19th century (1880-1905), at a time when neuropathology (a science and a word which had just been created by Charcot) was triumphant, recognized, admired, neurology became institutionalized in its place, for the anatomical, physiological and clinical study of diseases of the nervous system. Gradually, emptied of its content, in favour of neurology, neuropathology then entered a period of semantic and institutional uncertainly which only ended with its second "true-false" institutionalization, starting in the 1950s, at the cost of its reduction to pathologic anatomy of the nervous system.

France↗
PubMed1996

Apolipoprotein E in the brain and its role in Alzheimer's disease.

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain response to injury. The coordinated expression of apoE and its main receptor, the apoE/apoB (LDL) receptor, appears to regulate the transport of cholesterol and phospholipids during the different phases of the reinnervation process. The recent discovery that a peculiar form of apoE, the apoE4, is strongly linked to both sporadic and familial late onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system (CNS) is particularly important in relation to the function of the cholinergic system which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence suggests that apoE4 allele has a direct impact on cholinergic function in AD.

Aged↗
PubMed1995

Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease.

Apolipoprotein E (apoE) is critical in the modulation of cholesterol and phospholipid transport between cells of different types. Human apoE is a polymorphic protein with three common alleles, APO epsilon 2, APO epsilon 3, and APO epsilon 4. ApoE4 is associated with sporadic and late-onset familial Alzheimer disease (AD). Gene dose was shown to have an effect on risk of developing AD, age of onset, accumulation of senile plaques in the brain, and reduction of choline acetyltransferase (ChAT) activity in the hippocampus of AD subjects. To characterize the possible impact of the apoE4 allele on cholinergic markers in AD, we examined the effect of apoE4 allele copy number on pre- and postsynaptic markers of cholinergic activity. ApoE4 allele copy number showed an inverse relationship with residual brain ChAT activity and nicotinic receptor binding sites in both the hippocampal formation and the temporal cortex of AD subjects. AD cases lacking the apoE4 allele showed ChAT activities close or within age-matched normal control values. The effect of the apoE4 allele on cholinomimetic drug responsiveness was assessed next in a group (n = 40) of AD patients who completed a double-blind, 30-week clinical trial of the cholinesterase inhibitor tacrine. Results showed that > 80% of apoE4-negative AD patients showed marked improvement after 30 weeks as measured by the AD assessment scale (ADAS), whereas 60% of apoE4 carriers had ADAS scores that were worse compared to baseline. These results strongly support the concept that apoE4 plays a crucial role in the cholinergic dysfunction associated with AD and may be a prognostic indicator of poor response to therapy with acetylcholinesterase inhibitors in AD patients.

Age of Onset↗
PubMed1995

Increased levels of statin, a marker of cell cycle arrest, in response to hippocampal neuronal injury.

Injured neurons in the CNS are known to synthesize high levels of proliferation related oncogene products and heat shock proteins without dividing. Statin is a cell cycle regulated nuclear phosphoprotein, selectively associated with the non-proliferative state in a wide variety of cell types. In the present study, neuronal statin was examined following lethal or sublethal neuronal injuries in the hippocampus of Alzheimer's disease patients, in rats receiving kainate lesions to the dorsal hippocampus and in entorhinal cortex lesioned rats. Immunolabelling of nuclear statin showed that statin immunoreactivity increased preferentially in CA1 pyramidal neurons of the hippocampus in Alzheimer's disease. In kainate lesioned rats, statin immunoreactivity was markedly induced in the CA3 hippocampal region in association with neuronal loss. Entorhinal cortex lesioned rats showed a transient induction of statin between 2 and 6 days post lesion in CA1 neurons. However, cell counts in entorhinal cortex lesioned rats remained unaltered in the CA1 and granule cell layers during the entire 30 day time course, indicating that increased statin levels are not secondary to neuronal degeneration and are not necessarily accompanied by irreversible neuronal death. It is concluded that, in addition to proliferation related gene products, neuronal injury induces an increase in levels of statin, a nuclear marker of cell cycle arrest. Furthermore, statin may be a potentially useful marker of injurious neuronal stress, even under conditions that do not necessarily lead to irreversible cell death.

Alzheimer Disease↗
PubMed1995

Parkinsonism and dilatation of the perivascular spaces (état criblé) of the striatum: a clinical, magnetic resonance imaging, and pathological study.

Two men, 89 and 83 years of age, presented with predominantly axial parkinsonian signs. In both cases, magnetic resonance imaging of the brain showed numerous small foci, delineating the striatum. The lesions had the same signal as cerebral spinal fluid in both T1 and T2 sequences. Postmortem examination of the brain showed numerous lacunes due to dilatation of the perivascular spaces, frequently associated with alterations of the surrounding brain parenchyma. Typical changes of Parkinson's disease were associated in one case. Such vascular changes may produce, or modify, a parkinsonian syndrome.

Aged↗
PubMed1995

Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease.

This study examines the relationship between the levels of apolipoprotein E (apoE) and apolipoprotein J (apoJ, also designated as clusterin) as a function of apoE genotype in the hippocampus and cortex of Alzheimer disease (AD) subjects. These two lipophilic proteins which are involved in the maintenance of lipid homeostasis are both synthesized in the brain by astrocytes. Results indicate a reduction of apoE levels in the hippocampus and frontal cortex that is proportional to the apoE4 allele dose. Conversely, apoJ (clusterin) levels were found to increase proportionately to the number of apoE4 allele dose. These results suggest a compensatory induction of apoJ (clusterin) in the brain of apoE4 AD subjects showing low brain levels of apoE.

Alzheimer Disease↗
PubMed1995

Effect of MPTP and L-deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain.

Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). However, it is unclear if altered antioxidant enzyme activity is sufficient to increase lipid peroxidation in PD. We therefore investigated if MPTP can alter the activity of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) and the level of lipid peroxidation. L-Deprenyl, prior to MPTP administration, is used to inhibit MPP+ formation and its subsequent effect on antioxidant enzymes. MPTP induced a threefold increase in SOD activity in the striatum of C57BL/6 mice. No parallel increase in GSH-PX or CAT activities was observed, while striatal lipid peroxidation decreased. At the level of the substantia nigra (SN), even though increases in CAT activity and reduction in SOD and GSH-PX activities were detected, lipid peroxidation was not altered. Interestingly, L-deprenyl induced similar changes in antioxidant enzymes and lipid peroxidation levels, as did MPTP. Taken together, these results suggest that an alteration in SOD activity, without compensatory increases in CAT or GSH-PX activities, is not sufficient to induce lipid peroxidation.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1995

Apolipoprotein E, synaptic plasticity and Alzheimer's disease.

Apolipoprotein E (apoE) has been studied extensively with regard to its role in plasma lipoprotein lipid transport. A role for apoE in the transport of membrane cholesterol and phospholipid in the central and peripheral nervous system has also been studied. Entorhinal cortex-lesioned rats have been used extensively to examine the molecular mechanisms associated with deafferentation and reinnervation in the CNS; studies of the role of apoE in this process using this animal model are described. In all human populations examined, three common apoE isoforms, apoE2, apoE3 and apoE4, result from multiple alleles epsilon 2, epsilon 3 and epsilon 4 at a single apoE genetic locus. These isoforms impart well-characterized functional differences in plasma lipoprotein transport, which are reviewed herein. Also discussed are less well-studied possible apoE-isoform specific differences in central nervous system function. These are currently of critical importance due to numerous recent studies showing an association of epsilon 4 with increased risk for Alzheimer's disease. Diverse hypotheses as to the molecular basis for this association, as well as the supporting experimental evidence, are reviewed.

Alzheimer Disease↗
PubMed1995

[Intra-extracranial meningioma in the cranial vault].

Between 1982 and 1993, 11 cases of intra-extracranial vault meningiomas were treated in Créteil, by the same multidisciplinary team. The average age was 53.5 years and the Karnofsky rating was high (> 80 in 7 cases). Ten of the 11 cases had medial tumours with venous sinus thrombosis occurring in 9 of these. The location of the tumour was frontal in 6 and parietal in 4 patients. Of the medial tumours, 5 (half) were bilateral intracranial lesions. The average duration of symptoms was more than 10 years in four cases, between 1 and 3 years in five, and the diagnosis was made immediately in two patients. MRI coronal sections, after venous contrast injection, allowed diagnosis of the lesion and visualisation of the sinus thrombosis. Embolisation was performed pre-operatively in all cases scheduled to have surgery, resulting in safe excision of the tumour. Surgery was performed in 9 patients with complete tumour removal achieved in 8. Of those who did not undergo surgery, one received radiotherapy and the other died before treatment. The bony defect was covered with cadaveric bone, autogenous bone, coral and methyl-methacrylate in one, two, two and two patients respectively. Complications occurred in 2 cases: extradural secondary infection and CSF rhinorrhea treated with a lumbo-peritoneal shunt. The post-operative Karnofsky rating was greater than 90 in seven cases, 70 in one, and 50 in two cases. After an average follow-up of 4 years, 3 patients had tumor recurrence at 4, 7, and 8 years; the first having a locally malignant character, the second showing radiological recurrence in a case of subtotal removal, and the third a marginal recurrence. Two of the 3 patients underwent further surgery. The malignant case, received radiotherapy but unfortunately a new recurrence occurred 14 months later. As radiotherapy was used in only 3 cases, statistically significant conclusions concerning efficacy cannot be drawn.

Adult↗
PubMed1995

[Extracerebral metastases of a glioblastoma, in the absence of surgery].

A 50 y.o. male presented with a right parietal tumor which was a glioblastoma on stereotactic biopsy. He was treated by radiation and steroids, with clinical improvement. Four months later, he presented with a left preauricular mass and cervical lymphadenopathy. CT scan showed destruction of the left mastoid and filling of the left tympanic cavity. One month later, he suffered progressive dyspnea. Chest X ray showed a mediastinal mass on the right side and numerous bilateral interstitial opacities in the lungs. A bronchial biopsy was inconclusive. His general condition worsened, and he died. Postmortem showed continuous neoplastic infiltration of the left part of the base of skull, extending into the neck. Numerous metastases were present in mediastinal lymph nodes, lung parenchyma, pleura and pleural aspect of the diaphragm. There were no subdiaphragmatic metastases. Neuropathological examination confirmed a poorly differentiated highly malignant glioblastoma with severe necrosis involving the internal part of the parietal lobe extending to the dura mater of the convexity and falx cerebri with invasion of the superior longitudinal sinus which was entirely occluded. The biopsy scar was not infiltrated. Visceral tumors were morphologically identical to the brain tumor. They were strongly GFAP positive and cytokeratin negative. Extraneural metastases of glioblastoma in the absence of surgery are uncommon in adults. Involvement of the dura mater and/or superior longitudinal sinus is an almost constant feature. In our case, this may have led to invasion of the base of skull and secondary regional, lymphatic, and hematogenous spread.

Brain Neoplasms↗
PubMed1994

Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies.

Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD.

Aged↗
PubMed1994

Statin, a marker of cell cycle arrest, is overexpressed during the early phase of delayed NMDA toxicity in hippocampal cell cultures.

Statin is a 57-kDa protein exclusively expressed in nuclei of nonproliferating mammalian cells. Recent studies have suggested that statin may play a role in the maintenance of growth arrest. Several lines of evidence also support the notion that a variety of genes and gene products are modulated during cell proliferation and cell death. The present study examined the possibility that statin expression could be modulated during neuronal injury using N-methyl-Daspartate (NMDA)-induced toxicity to rat embryonic hippocampal cultures as a model. Immunocytochemical studies using a monoclonal antibody to statin revealed a prominent nuclear localization of statin in cultured hippocampal cells. Western blot analysis showed that this antibody recognizes a 57-kDa protein band, indicative of the presence of statin in this preparation. Brief exposure of hippocampal neurons to NMDA (500 microM) produced severe neuronal degeneration over the subsequent hours. NMDA-treated neurons markedly overexpressed statin. Both NMDA-induced neuronal toxicity and statin overexpression were prevented by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohept-5,10-imine hydrogen maleate (MK-801). Interestingly, time course studies indicate that the increased expression of statin observed following NMDA exposure clearly preceded the appearance of the first signs of neuronal death as determined by vital staining. In addition, exposure of hippocampal neurons to the Ca2+ ionophore, A23187, produced a marked increase in statin immunodetection, indicating that statin expression is likely regulated in a Ca(2+)-dependent manner. Thus, these results show that statin, which is expressed at low levels in embryonic rat cultured hippocampal neurons, is rapidly overexpressed following a toxic insult produced by the activation of the NMDA receptor. The observation that statin overexpression occurs prior to neuronal death raises the possibility that the up-regulation of statin could be used as an early index of neuronal injury.

Animals↗
PubMed1994

Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease.

Recent evidence indicates that apolipoprotein E (ApoE) plays a central role in the hippocampal response to injury. The co-ordinated expression of ApoE and its receptor, the ApoE/ApoB [low density lipoprotein (LDL)] receptor, appears to regulate the transport of cholesterol and phospholipids during the early and intermediate phases of the reinnervation process. During dendritic remodeling and synaptogenesis, neurons progressively repress the synthesis of cholesterol in favor of cholesterol internalization through the ApoE/LDL receptor pathway. The discovery that the epsilon 4 allele is strongly linked to both sporadic and familial late-onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid-transport system associated with compensatory sprouting and synaptic remodeling could be central to the AD process. The role of ApoE in the CNS is particularly important in relation to the function of the cholinergic system, which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence suggests that the epsilon 4 allele has a direct impact on cholinergic function in AD.

Alzheimer Disease↗
PubMed1994

Regulation of 1,4,5-IP3, 1,3,4,5-IP4 and IP6 binding sites following entorhinal cortex lesions in rat brain.

A lesion of the entorhinal cortex produces a loss of more than 80% of the synapses in the outer molecular layer of the hippocampus in the rat. However, this synaptic loss is transient. Beginning a few days after denervation, new synapses are formed, virtually replacing the lost inputs within two months. Synaptic remodelling induced by entorhinal cortex lesion is associated with specific modifications of various neurotransmitters, hormones and growth factors. Many of these substances act at membrane bound-receptors to induce the hydrolysis of phosphatidylinositols generating various inositol phosphates. Some of the key members of this family include inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate which are all associated with the maintenance Ca2+ homeostasis. To investigate the potential roles and/or alterations of inositol phosphates in entorhinal cortex lesions-induced neuronal plasticity, we quantified specific receptor sites for inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate using their respective tritiated ligands, at different periods post-lesion corresponding to the degenerative and subsequent reinnervation phases. [3H]inositol 1,4,5-trisphosphate binding sites are maximally increased (30%) between two and eight days post-lesion in the hippocampal formation on both sides of the lesion. In the cortex, [3H]inositol 1,4,5-trisphosphate binding increased also bilaterally following the lesion. Changes in [3H]inositol 1,3,4,5-tetrakisphosphate binding are delayed and reduced (20% increase) in magnitude compared to these seen for [3H]inositol 1,4,5-trisphosphate binding. The maximal peak in [3H]inositol 1,3,4,5-tetrakisphosphate binding is observed between eight and 14 days after the lesion in the hippocampal formation and the cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[J.M. Charcot's library at the Salpêtrière Hospital in Paris].

In 1906, the personal scientific books collection of J.M. Charcot (1825-1893) was bequeathed by his son, the explorer J.B. Charcot, to the Neurological Disease Unit-Salpêtrière Hospital in Paris. This library died progressively. In the same time, so did the Anatomical Museum, founded to by J.M. Charcot, and also settled in the "Division Pariset". Since 1966, with help of the late Professeur P. Castaigne, and collaborators, the library is reviving. It increased with several gifts of personal libraries, from Dr. Souques, Pr. Mollaret, Pr. Alajouanine, Pr. Lhermitte, Pr. Signoret. It is now the "Bibliothèque de Neurosciences J.M. Charcot-Paris VI University".

France↗
PubMed1994

Multiple cholinergic markers are unexpectedly not altered in the rat dentate gyrus following entorhinal cortex lesions.

Since major cholinergic deficits are observed in Alzheimer's disease, the development of models to study possible cholinergic plasticity has generated great interest. In this regard, it has been shown that lesions of the entorhinal cortex, which sends glutamatergic projections to the hippocampus, promote the sprouting and plasticity of presumptive cholinergic septohippocampal fibers in the dentate gyrus, as revealed by AChE histochemistry. This sprouting was reported to be evident at 8 d and up to 30 d postlesion (DPL) and is now widely used as a model of cholinergic neuronal plasticity. In the present study, unilateral lesions of the entorhinal cortex were made in adult rats, and the status of various putative pre- and postsynaptic cholinergic markers was assessed after 2, 4, 8, 14, and 30 DPL. As expected, AChE was increased in the outer molecular layer of the ipsilateral dentate gyrus from 8 to 30 DPL. In contrast, the activity of ChAT, the enzyme responsible for the synthesis of ACh, and the densities of specific binding sites for 3H-AH5 183/vesamicol (blocker of the ACh vesicular transport sites), 3H-hemicholinium-3 (blocker of the high-affinity choline uptake sites), muscarinic-M2 (3H-AF-DX 384 and 3H-ACh), muscarinic-M1 (3H-pirenzepine), and nicotinic (3H-N-methylcarbamylcholine) cholinergic receptors were not increased on the ipsilateral molecular layer of the dentate gyrus, as compared to their contralateral controls. We conclude that the increase in AChE staining in the molecular layer of the dentate gyrus following entorhinal cortex lesions may be due to changes in noncholinergic neurons.

Acetylcholine↗