Biomedical subjects

Anne Bernard

Publications and source records attributed to Anne Bernard.

5 recordsLinked to original sources

PubMed2006

Matrix metalloproteinase-2 (MMP-2) regulates astrocyte motility in connection with the actin cytoskeleton and integrins.

Matrix Metalloproteinases (MMPs) play a role in migration of many cell types outside the central nervous system (CNS). Among neural cells, astrocytes are one of the main sources of MMPs in physiological and postlesional conditions. However, no data are available on the possible role of MMPs in astrocyte motility. Using an in vitro model of 2D migration and broad spectrum and selective MMP inhibitors, the authors demonstrated that MMP-2, but not MMP-9, is a key enzyme for astrocyte migration. In support of these data, the authors found constitutive expression of MMP-2 in astrocytes, while MMP-9 was nearly undetectable by gel zymography and immunocytochemical methods. The inhibition of migration by MMP inhibitors correlated with changes in cell morphology and in the organization of the actin cytoskeleton. In parallel, the characteristic focalized distribution of MMP-2 at the migration front observed in control cells became more diffuse and internalized by treatments that inhibited migration. The disruption of actin by cytochalasin D caused the partial recruitment of MMP-2 and gelatinolytic activity into actin aggregates, indicating a connection between the proteinase and the actin cytoskeleton. Finally, the authors found a co-localization of beta1-integrin with MMP-2 at the leading edge of migrating astrocytes. Altogether, these data provide the first evidence for the implication of MMP-2 in astrocyte motility, probably through the interaction of the proteinase with beta1-integrin that could act as a linker between pericellular proteolysis and the actin cytoskeleton.

Actins↗

PubMed2005

Magnet demographic data: creating a system to streamline the process.

The benefits of Magnet status are well documented. However, the challenges of completing the Magnet application can overextend an organization's data collection processes and systems. The authors discuss the driving forces behind development of Step One, a cost-effective on-line system alternative to manual demographic data collection. The article presents an overview of staff's role in system development and rollout and describes improvements in efficiency, accuracy, and satisfaction from data collection to final American Nurse Credentialing Center report generation.

Benchmarking↗

PubMed2005

Tissue inhibitor of metalloproteinases-1 (TIMP-1) modulates neuronal death, axonal plasticity, and learning and memory.

The tissue inhibitor of metalloproteinases-1 (TIMP-1) belongs to a family of multifunctional proteins that inhibit matrix metalloproteinases (MMPs), but also regulate cell growth, proliferation, migration and apoptosis in non-nervous tissues. We had previously reported that kainate (KA)-mediated excitotoxic seizures induce the expression of TIMP-1 in resistant neurons and reactive astrocytes of the rat CNS, but the functional implications of these changes had not been elucidated. In the present work we used a targeted gene null mutation in mice to investigate in vivo the involvement of TIMP-1 in neuronal death and axonal sprouting following KA. We found no differences in seizure behaviour between the wild-type (WT) and the TIMP-1 knock-out (KO) mice, without any compensation by other TIMPs, at least at the mRNA level. However, the TIMP-1 KO mice were resistant to excitotoxicity and did not undergo the typical mossy fibre sprouting observed in WT mice. The lack of TIMP-1 paradoxically hampered the increase in the activity of MMPs observed in the seizing WT mice. In addition, we demonstrate that learning and memory are impaired in untreated KO mice. In conclusion, this study provides the first in vivo evidence for the implication of TIMP-1 in neuronal death and axonal sprouting in a pathological situation, but also suggests the involvement of TIMP-1 in the synaptic mechanisms underlying learning and memory in physiological conditions. More generally, these data support the idea that the control of proteolysis is instrumental for pathological and physiological processes in the brain.

Animals↗

PubMed2004

[The MMP/TIMP system in the nervous system].

The matrix metalloproteinases (MMP) belong to a growing family of secreted or membrane-bound (MT-MMP) enzymes that cleave protein components of the extracellular matrix and bioactive factors involved in intercellular signaling. MMP activity is counterbalanced by their four physiological inhibitors, the tissue inhibitors of MMP (TIMPs). Together, MMP and TIMP control cell-cell and cell-matrix interactions associated with physiological processes. However, the breakdown of the protease-inhibitor balance may lead to the loss of tissue homeostasis and the development of degenerative and tumorigenic processes in various tissues. The emerging idea is that the MMP/TIMP system also plays a major role in the pathology and physiology of the nervous system and that mastering MMP activity will set the basis for new and more efficient therapeutic strategies against nervous system disorders.

Blood-Brain Barrier↗

PubMed2003

[Matrix metalloproteinases and their inhibitors, modulators of neuro-immune interactions and of pathophysiological processes in the nervous system].

The matrix metalloproteinases (MMPs) belong to a growing family of Zn2+-dependent endopeptidases, secreted or membrane-bound (MT-MMP), that regulate or degrade by proteolytic cleavage protein components of the extracellular matrix, cytokines, chemokines, cell adhesion molecules and a variety of membrane receptors. MMP activity is counterbalanced by their physiological inhibitors, the tissue inhibitors of MMPs (TIMPs), a family of 4 secreted multifunctional proteins that have growth promoting activities. In physiological conditions MMP activity is tightly regulated and altered MMP regulation is associated with pathological processes including inflammation, cell proliferation, cell death and tissue remodeling. The MMP/TIMP system is involved in the development and function of cells of the immune system by promoting their differentiation, activation, migration across basement membranes and tissues. In the last years, data has accumulated indicating that the MMP/TIMP system is expressed in the nervous system where it regulates neuro-immune interactions and plays a major role in pathophysiological processes. In this review, we present recent in vivo and in vitro studies that highlight the contribution of the MMP/TIMP system to various diseases of the nervous system, involving blood brain barrier breakdown, neuroinflammation, glial reactivity, neuronal death, reactive plasticity, and to developmental and physiological processes including cell migration, axonal sprouting and neuronal plasticity. This review also alludes to the beneficial effects of synthetic MMP inhibitors in different animal models of neuropathology. In all, a further understanding of the role of MMPs and TIMPs in the nervous system should contribute to unravel mechanisms of neuronal plasticity and pathology and set the basis of new therapeutic strategies in nervous system disorders based on the development of synthetic MMP inhibitors.

Animals↗