Primary papillary tumors of the central nervous system are rare. We have encountered a series of six papillary tumors of the pineal region with distinctive features that appear to represent a clinicopathologic entity. The tumors occurred in four women and two men, ranging in age from 19 to 53 years. Imaging studies showed a large well-circumscribed mass in the pineal region. The tumors were characterized by an epithelial-like growth pattern, in which the vessels were covered by a layer of tumoral cells. In papillary areas, the neoplastic cells were large, columnar or cuboidal, with a clear cytoplasm. Nuclei, round or infolded, were found generally at the basal pole of tumoral cells. Immunohistochemically, the tumor cells showed strong staining for cytokeratin, S-100 protein, neuron-specific enolase, and vimentin but only weak or no staining for epithelial membrane antigen and glial fibrillary acid protein. Ultrastructural examination of two cases revealed abundant rough endoplasmic reticulum with distended cisternae filled with secretory product, microvilli, and perinuclear intermediate filaments. The morphofunctional features of these papillary tumors of the pineal region, remarkably uniform within this series, are similar to those described for ependymal cells of the subcommissural organ, and the papillary tumors of the pineal region may be derived from these specialized ependymocytes.

Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade the components of the extracellular matrix (ECM). The balance between MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] in the pericellular environment determines the most significant proteolytic events in tissue remodeling. In vitro evidence is accumulating that these molecules may be crucial in the maturation of neural cells. Here, we investigated the in vivo expression of MMPs 2, 3, and 9 and TIMPs 1, 2, and 3 in the developing and adult rat cerebellum using immunohistochemistry and in situ hybridization. During postnatal development, all Purkinje (PK) cell somata expressed all the MMPs and TIMPs studied, whereas their growing dendritic trees expressed only MMP 3 and TIMP 3. In the adult, MMP 3 was confined to PK cell bodies, whereas TIMP 3 was expressed in PK cell somata and processes. Irrespective of the developmental stage, Bergmann glial processes contained only MMP 9, but their somata contained both TIMP 1 and MMP 9. In granular cells, MMPs 3 and 9 and TIMPs 1, 2, and 3 were chiefly detected at a time when migration is known to be maximal; except for that of TIMP 1, their expression persisted in the internal granular layer in the adult. The functional relevance of MMP expression was verified by gelatin zymography. MMP 9 activity was maximal on postnatal day 10 (P10) and was detectable at a low level on P15 and in the adult, whereas MMP 2 activity remained similar throughout postnatal development. Regional and cell-specific expression of MMPs and TIMPs closely reflects the successive stages of cerebellar development, thereby suggesting a pivotal role for ECM proteolysis in brain development and plasticity.

The lack of draining lymphatic vessels in the central nervous system (CNS) contributes to the so-called "CNS immune privilege." However, despite such a unique anatomic feature, dendritic cells (DCs) are able to migrate from the CNS to cervical lymph nodes through a yet unknown pathway. In this report, labeled bone marrow-derived myeloid DCs were injected stereotaxically into the cerebrospinal fluid (CSF) or brain parenchyma of normal rats. We found that DCs injected within brain parenchyma migrate little from their site of injection and do not reach cervical lymph nodes. In contrast, intra-CSFinjected DCs either reach cervical lymph nodes or, for a minority of them, infiltrate the subventricular zone, where neural stem cells reside. Surprisingly, DCs that reach cervical lymph nodes preferentially IntroductionUnder normal conditions, the transport of immune cells from blood to the central nervous system (CNS) is restricted by 2 physical barriers: the blood-brain barrier formed by CNS parenchymal microvessels and the blood cerebrospinal fluid (CSF) barrier formed by the choroid plexuses. Also, the circulation of immune cells from brain to lymphoid organs is hampered by the lack of CNS-draining lymphatic vessels. Nevertheless, immune responses may develop in the CNS, and cervical lymph nodes are considered as major sites of antigen presentation during neuroinflammatory diseases. 1,2 Indeed, antigens are drained from the CNS to cervical lymph nodes along the axons of craniofacial peripheral nerves. 3,4 Also, it was reported that dendritic cells (DCs) are able to migrate out of the CNS and, in turn, to elicit a CNS-targeted immune response. 5,6 However, it is not clear whether DCs circulating out of the CNS actually migrate from brain parenchyma or from the CSF compartment. This point is of importance because DCs are absent from normal CNS parenchyma, 7 but they can be detected in CSF and in compartments associated with CSF circulation or production, including meninges and choroid plexuses. [8][9][10] Moreover, under neuroinflammatory conditions, DCs accumulate in the CSF 11,12 as well as in perivascular spaces, 13,14 anatomic compartments draining into the CSF. These findings, along with others, suggest that the CSF may be a major transport route for DCs circulating in the CNS and migrating either from CSF to CNS parenchyma or from CSF to the lymphoid organs. 11,12,15,16 In the present study, we tracked bone marrow-derived myeloid DCs injected stereotaxically into the CSF or brain parenchyma of rats under normal conditions. Materials and methods AnimalsAnimal care and procedures were conducted according to the guidelines approved by the French Ethical Committee (decree 87-848) and the European Community directive 86-609-EEC and meet the Neuroscience Society guidelines. The study protocol was approved by the ethical committee of Faculté de Médecine Laennec, Lyon, France. Eight-to 10-week-old female Sprague Dawley rats were obtained from Harlan (Gannat, France). ReagentsMurine GM-CSF, human Flt3-L, murine IL-4, and h...

No abstract

No abstract

No abstract

In absence epilepsy, epileptogenic processes are suspected of involving an imbalance between GABAergic inhibition and glutamatergic excitation. Here, we describe alteration of the expression of glutamate transporters in rats with genetic absence (the Genetic Absence Epilepsy Rats from Strasbourg: GAERS). In these rats, epileptic discharges, recorded in the thalamo-cortical network, appear around 40 days after birth. In adult rats no alteration of the protein expression of the glutamate transporters was observed. In 30-day-old GAERS protein levels (quantified by western blot) were lower in the cortex by 21% and 35% for the glial transporters GLT1 and GLAST, respectively, and by 32% for the neuronal transporter EAAC1 in the thalamus compared to control rats. In addition, the expression and activity of GLAST were decreased by 50% in newborn GAERS cortical astrocytes grown in primary culture. The lack of modification of the protein levels of glutamatergic transporters in adult epileptic GAERS, in spite of mRNA variations (quantified by RT-PCR), suggests that they are not involved in the pathogeny of spike-and-wave discharges. In contrast, the alteration of glutamate transporter expression, observed before the establishment of epileptic discharges, could reflect an abnormal maturation of the glutamatergic neurone-glia circuitry. Keywords: cortex, EAAC1, GAERS, GLAST, GLT1, thalamus. Absence epilepsy is mainly a childhood disease. Seizures occur as frequently as several hundred times per day and are detrimental to children's education and health. While convulsive epilepsy has been widely investigated, little is known about the pathophysiology of absence seizures. In GAERS (Genetic Absence Epilepsy Rats from Strasbourg), a genetic model of absence epilepsy (Vergnes et al. 1982), epileptic seizures occur around 40 days after birth and persist throughout lifetime. As in the human disease, the neuronal hyperexcitation and hypersynchronization, which induce spike-and-wave discharges (SWDs) in GAERS, are generated in a cortico-thalamic loop, involving reciprocal glutamatergic projections between the thalamus and the cortex, as well as GABAergic interneurones. Involvement of GABA and glutamate in the initiation and spreading of epileptic discharges in this model is supported by electrophysiological and pharmacological studies. A significantly increased amplitude of the voltage-dependent low-threshold Ca 2+ current observed in the reticular thalamic nucleus of GAERS with established epilepsy suggests an alteration of the GABAergic neurones in this structure (Tsakiridou et al. 1995). GABA A and GABA B agonists increase the duration of SWDs, while GABA B antagonists suppress SWDs. In addition, agonists of the glutamate receptor AMPA increase SWDs, while AMPA and NMDA antagonists decrease and suppress them, respectively. Density of GABAergic or glutamatergic neurones, glutamate decarboxylase expression (GABA synthesizing enzyme) and density of GABA

No abstract