Late Bone Marrow Mononuclear Cell Transplantation in Rats with Sciatic Nerve Crush: Analysis of a Potential Therapeutic Time Window.

After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study, we analyze whether there is a temporal window in which BMMCs migrate more efficiently to damaged nerves while still retaining their positive effects.

Cytosolic phospholipase A regulates lipid homeostasis under osmotic stress through PPARγ.

Physiologically, renal medullary cells are surrounded by a hyperosmolar interstitium. However, different pathological situations can induce abrupt changes in environmental osmolality, causing cell stress. Therefore, renal cells must adapt to survive in this new condition.

Small-angle X-ray scattering to quantify the incorporation and analyze the disposition of magnetic nanoparticles inside cells.

Access to detailed information on cells loaded with nanoparticles with nanoscale precision is of a long-standing interest in many areas of nanomedicine. In this context, designing a single experiment able to provide statistical mean data from a large number of living unsectioned cells concerning information on the nanoparticle size and aggregation inside cell endosomes and accurate nanoparticle cell up-take is of paramount importance. Small-angle X-ray scattering (SAXS) is presented here as a tool to achieve such relevant data.

Sciatic nerve regeneration after traumatic injury using magnetic targeted adipose-derived mesenchymal stem cells.

Traumatic peripheral nerve injuries constitute a huge concern to public health. Nerve damage leads to a decrease or even loss of mobility of the innervated area. Adult stem cell therapies have shown some encouraging results and have been identified as promising treatment candidates for nerve regeneration.

DMT1 iron uptake in the PNS: bridging the gap between injury and regeneration.

Previous studies by our group demonstrated the key role of iron in Schwann cell maturation through an increase in cAMP, PKA activation and CREB phosphorylation. These studies opened the door to further research on non-transferrin-bound iron uptake, which revealed the presence of DMT1 mRNA all along SC progeny, hinting at a constitutive role of DMT1 in ensuring the provision of iron in the PNS. In light of these previous results, the present work evaluates the participation of DMT1 in the remyelination process following a demyelinating lesion promoted by sciatic nerve crush--a reversible model of Wallerian degeneration.

Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells.

The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P(0) and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin-forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot.

Presence of alpha-globin mRNA and migration of bone marrow cells after sciatic nerve injury suggests their participation in the degeneration/regeneration process.

We have previously reported that in the distal stump of ligated sciatic nerves, there is a change in the distribution of myelin basic protein (MBP) and P0 protein immunoreactivities. These results agreed with the studies of myelin isolated from the distal stump of animals submitted to ligation of the sciatic nerve, showing a gradual increase in a 14 kDa band with an electrophoretic mobility similar to that of an MBP isoform, among other changes. This band, which was resolved into two bands of 14 and 15 kDa using a 16% gel, was found to contain a mixture of MBP fragments and peptides with great homology with alpha- and beta-globins.

Nerve degeneration is prevented by a single intraneural apotransferrin injection into colchicine-injured sciatic nerves in the rat.

In this work, we have immunohistochemically analyzed the effects of single injections of apotransferrin (aTf) on the expression of myelin (myelin basic proteins [MBPs]) and axonal (protein gene product 9.5 [PGP 9.5] and beta(III)-tubulin [beta(III)-tub]) proteins in colchicine-injected and crushed sciatic nerves of adult rats.

P0 and myelin basic protein-like immunoreactivities following ligation of the sciatic nerve in the rat.

In this work we analyzed variations in the expression of MBPs and P0 in ligated sciatic nerves of young and adult rats at 3, 7, and 14 days postligation (PL), by immunohistochemistry and SDS-PAGE of isolated myelin. A protein redistribution was seen in the distal stump of ligated nerves with the appearance of immunoreactive clusters. Using the KS400 image analyzer, immunostained area values were obtained from the different nerves dissected.

HoloTransferrin but not ApoTransferrin prevents Schwann cell de-differentiation in culture.

Schwann cells (SCs) in culture, without the presence of axons, become de-differentiated, reaching a condition similar to that of their precursor cells. The cytoplasmic accumulation of transferrin (Tf) in the myelinated peripheral nerve has been reported and data in the literature support a role for apoTf in myelination in the CNS. In the present report, we used SC cultures to evaluate the capacity of apoTf and holoTf to prevent cell de-differentiation promoted by fetal calf serum deprivation.

High glucose concentrations stimulate renal papillary phosphatidylcholine biosynthesis.

The effects of a high glucose concentration (HGC) on renal phosphatidylcholine (PtdCho) biosynthesis were studied. In control rats, HGC increased papillary PtdCho biosynthesis. In chronic diabetic rats, an increase above that induced by diabetes was observed.

Renal phospholipid metabolism in streptozotocin-induced diabetic rats.

The effect of acute and chronic streptozotocin-induced diabetes on phospholipid metabolism in papillary, medullary and cortical slices was studied. No changes were observed in either the phospholipid content or composition in the papilla, medulla and cortex from acute and chronic diabetic rats. With reference to (U-14C)glycerol incorporation in the papilla from chronic diabetic rats, it increased in PtdCho, PtdIns and PtdEtn.

Is the increase in renal papillary phospholipid biosynthesis a protective mechanism against injury?

Mercuric chloride (HgCl2) is a well-known renal toxic that causes acute renal failure. The effect of HgCl2 treatment and the protection by thyroxine were studied in rat renal papilla (P), outer medullary inner stripe (OMIS), outer medullary outer stripe (OMOS) and cortical phospholipids (PhLs). HgCl2 brought about an increase in the total phospholipid content in P and OMIS but a drop in OMOS and cortex.

Specific and functional insulin receptors in rat renal papilla.

To investigate a possible action of insulin on the rat kidney papilla, the binding of 125I-insulin to papilla microsomes was examined. This binding was specific to insulin in that it was displaced by increasing concentrations of unlabelled porcine insulin and to a lesser extent by porcine proinsulin and IGF-I, but not by IGF-II and bGH. Scatchard plot of the binding data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that showed negative cooperativity.