Glial response to 17β-estradiol in neonatal rats with excitotoxic brain injury.

White-matter injury is the most common cause of the adverse neurodevelopmental outcomes observed in preterm infants. Only few options exist to prevent perinatal brain injury associated to preterm delivery. 17β-estradiol (E2) is the predominant estrogen in circulation and has been shown to be neuroprotective in vitro and in vivo.

Inhaled NO prevents hyperoxia-induced white matter damage in neonatal rats.

White matter damage (WMD) and bronchopulmonary dysplasia (BPD) are the two main complications occurring in very preterm infants. Inhaled nitric oxide (iNO) has been proposed to promote alveolarization in the developing lung, and we have reported that iNO promotes myelination and induces neuroprotection in neonatal rats with excitotoxic brain damage. Our hypothesis is that, in addition to its pulmonary effects, iNO may be neuroprotective in rat pups exposed to hyperoxia.

Use of human umbilical cord blood mononuclear cells to prevent perinatal brain injury: a preclinical study.

Cerebral palsy (CP) is the most frequent neurological disorder associated with perinatal injury of the developing brain. Major brain lesions associated with CP are white matter damage (WMD) in preterm infants and cortico-subcortical lesions in term newborns. Cell therapy is considered promising for the repair of brain damage.

Transplantation of umbilical cord-derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives.

The prevention of perinatal neurological disabilities remains a major challenge for public health, and no neuroprotective treatment to date has proven clinically useful in reducing the lesions leading to these disabilities. Efforts are, therefore, urgently needed to test other neuroprotective strategies including cell therapies. Although stem cells have raised great hopes as an inexhaustible source of therapeutic products that could be used for neuroprotection and neuroregeneration in disorders affecting the brain and spinal cord, certain sources of stem cells are associated with potential ethical issues.

Stem cell therapy for neonatal brain injury: perspectives and challenges.

Cerebral palsy is a major health problem caused by brain damage during pregnancy, delivery, or the immediate postnatal period. Perinatal stroke, intraventricular hemorrhage, and asphyxia are the most common causes of neonatal brain damage. Periventricular white matter damage (periventricular leukomalacia) is the predominant form in premature infants and the most common antecedent of cerebral palsy.

Implanted neurosphere-derived precursors promote recovery after neonatal excitotoxic brain injury.

Brain damage through excitotoxic mechanisms is a major cause of cerebral palsy in infants. This phenomenon usually occurs during the fetal period in human, and often leads to lifelong neurological morbidity with cognitive and sensorimotor impairment. However, there is currently no effective therapy.

Nitric oxide plays a key role in myelination in the developing brain.

Inhaled nitric oxide (iNO) is one of the most promising therapies used in neonates, but there is little information available about its effect on the developing brain. We explored the effects of both iNO and endogenous NO on developing white matter in rodents. Rat or mouse pups and their mothers were placed in a chamber containing 5 to 20 ppm of NO for 7 days after birth.

Dynamic conformational changes in the FERM domain of FAK are involved in focal-adhesion behavior during cell spreading and motility.

Focal adhesion kinase (FAK) controls cellular adhesion and motility processes by its tight link to integrin- and extracellular-matrix-mediated signaling. To explore the dynamics of the regulation of FAK, we constructed a FRET-based probe that visualizes conformational rearrangements of the FERM domain of FAK in living cells. The sensor reports on an integrin-mediated conformational change in FAK following cellular adhesion.

Reversal of cell polarity and actin-myosin cytoskeleton reorganization under mechanical and chemical stimulation.

To study reorganization of the actin system in cells that invert their polarity, we stimulated Dictyostelium cells by mechanical forces from alternating directions. The cells oriented in a fluid flow by establishing a protruding front directed against the flow and a retracting tail. Labels for polymerized actin and filamentous myosin-II marked front and tail.

Time-resolved responses to chemoattractant, characteristic of the front and tail of Dictyostelium cells.

In a gradient of chemoattractant, Dictyostelium cells are orientated with their front directed toward the source and their tail pointing into the opposite direction. The front region is specified by the polymerization of actin and the tail by the recruitment of filamentous myosin-II. We have dissected these front and tail responses by exposing cells to an upshift of cyclic AMP.

Calcium mobilization stimulates Dictyostelium discoideum shear-flow-induced cell motility.

Application of hydrodynamic mild shear stress to adherent Dictyostelium discoideum vegetative cells triggers active actin cytoskeleton remodeling resulting in net cell movement along the flow. The average cell speed is strongly stimulated by external calcium (Ca2+, K50%=22 microM), but the directionality of the movement is almost unaffected. This calcium concentration is ten times higher than the one promoting cell adhesion to glass surfaces (K50%=2 microM).

Phg2, a kinase involved in adhesion and focal site modeling in Dictyostelium.

The amoeba Dictyostelium is a simple genetic system for analyzing substrate adhesion, motility and phagocytosis. A new adhesion-defective mutant named phg2 was isolated in this system, and PHG2 encodes a novel serine/threonine kinase with a ras-binding domain. We compared the phenotype of phg2 null cells to other previously isolated adhesion mutants to evaluate the specific role of each gene product.

Shear flow-induced motility of Dictyostelium discoideum cells on solid substrate.

Application of a mild hydrodynamic shear stress to Dicytostelium discoideum cells, unable to detach cells passively from the substrate, triggers a cellular response consisting of steady membrane peeling at the rear edge of the cell and periodic cell contact extensions at its front edge. Both processes require an active actin cytoskeleton. The cell movement induced by the hydrodynamic forces is very similar to amoeboid cell motion during chemotaxis, as for its kinematic parameters and for the involvement of phosphatidylinositol(3,4,5)-trisphosphate internal gradient to maintain cell polarity.