Short-Term exposure of umbilical cord blood CD34+ cells to human platelet lysate and cytokines enhances engraftment.

Background: Intra bone marrow (IBM) injection has been proposed as a strategy to bypass homing inefficiencies associated with intravenous (IV) hematopoietic progenitor stem cell (HSPC) transplantation and thus increases the number of HSPC that engraft. Despite physical delivery into the bone marrow cavity, many donor cells are rapidly redistributed by vascular perfusion. Thus, the objective of our study was to evaluate the ability of human platelet lysates (hPL) to improve HSPC retention into the bone marrow and consequently to improve engraftment.

A valuable animal model of spinal cord injury to study motor dysfunctions, comorbid conditions, and aging associated diseases.

Most animal models of contused, compressed or transected spinal cord injury (SCI) require a laminectomy to be performed. However, despite advantages and disadvantages associated with each of these models, the laminectomy itself is generally associated with significant problems including longer surgery and anaesthesia (related post-operative complications), neuropathic pain, spinal instabilities, deformities, lordosis, and biomechanical problems, etc. This review provides an overview of findings obtained mainly from our laboratory that are associated with the development and characterization of a novel murine model of spinal cord transection that does not require a laminectomy.

Pharmacological approaches to chronic spinal cord injury.

Although research on neural tissue repair has made enormous progress in recent years, spinal cord injury remains a devastating condition for which there is still no cure. In fact, recent estimates of prevalence in the United States reveal that spinal cord injury has undergone a five-fold increase in the last decades. Though, it has become the second most common neurological problem in North America after Alzheimer's disease.

Interaction between intravenous immunoglobulin (IVIg) and the low-density lipoprotein receptor-related protein 1: a role for transcytosis across the blood brain barrier?

Intravenous immunoglobulin (IVIg) is a therapeutic preparation of plasma-derived human IgG and is increasingly used for the treatment of several neurological inflammatory disorders. However, it is not clear whether the IgG molecules contained in IVIg can actually cross the BBB in treated patients. We recently showed that LRP1, an endocytic receptor involved in transcytosis of several proteins across the BBB was able to interact with IVIg.

Functional and physiological effects of treadmill training induced by buspirone, carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.

Background: Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss.

Objective: The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures.

Effects on locomotion, muscle, bone, and blood induced by a combination therapy eliciting weight-bearing stepping in nonassisted spinal cord-transected mice.

Background: The health benefits associated with physical activity-based rehabilitation in patients with no lower-extremity motor function after a spinal cord injury (SCI) is uncertain.

Methods: The authors assessed signs of efficacy, safety, and utility associated with a novel pharmacological combination therapy to activate central pattern generator (CPG) activity and corresponding locomotor activity in complete thoracic Th9/10-transected mice.

Results: Subcutaneous administration 4 times per week for 1 month of 1.

Traumatic and nontraumatic spinal-cord-injured patients in Quebec, Canada. Part 3: pharmacological characteristics.

Study Design: Community-based, cross-sectional study.

Objectives: This study aimed at examining and comparing the pharmacological treatments administered to traumatic and nontraumatic spinal-cord-injured patients (TSCI, NTSCI).

Setting: The Interval Rehabilitation Center, Trois-Rivieres, Province of Quebec, Canada.

Relation of vertebral deformities to bone density, structure, and strength.

Because they are not reliably discriminated by areal bone mineral density (aBMD) measurements, it is unclear whether minimal vertebral deformities represent early osteoporotic fractures. To address this, we compared 90 postmenopausal women with no deformity (controls) with 142 women with one or more semiquantitative grade 1 (mild) deformities and 51 women with any grade 2-3 (moderate/severe) deformities. aBMD was measured by dual-energy X-ray absorptiometry (DXA), lumbar spine volumetric bone mineral density (vBMD) and geometry by quantitative computed tomography (QCT), bone microstructure by high-resolution peripheral QCT at the radius (HRpQCT), and vertebral compressive strength and load-to-strength ratio by finite-element analysis (FEA) of lumbar spine QCT images.

Effects of co-administration of clenbuterol and testosterone propionate on skeletal muscle in paraplegic mice.

Spinal cord injury (SCI) is generally associated with a rapid and significant decrease in muscle mass and corresponding changes in skeletal muscle properties. Although beta(2)-adrenergic and androgen receptor agonists are anabolic substances clearly shown to prevent or reverse muscle wasting in some pathological conditions, their effects in SCI patients remain largely unknown. Here we studied the effects of clenbuterol and testosterone propionate administered separately or in combination on skeletal muscle properties and adipose tissue in adult CD1 mice spinal-cord-transected (Tx) at the low-thoracic level (i.

Traumatic and non-traumatic spinal cord-injured patients in Quebec, Canada. Part 2: biochemical profile.

Study Design: Community-based, cross-sectional study.

Objectives: This study aimed at examining and comparing biochemical profiles (blood and urine) of traumatic and non-traumatic spinal cord-injured patients (TSCIs vs NTSCIs).

Setting: The Interval Rehabilitation Center, Trois-Rivieres, Province of Quebec, Canada.

Oral administration of a tri-therapy for central pattern generator activation in paraplegic mice: proof-of-concept of efficacy.

Spinal cord injury (SCI) is a neurological condition, for which no cure exists, typically leading to an immediate and irreversible loss of sensory and voluntary motor functions accompanied by significant health problems. We conducted proof-of-concept experiments aimed at assessing efficacy upon oral administration of a novel combination therapy for central pattern generator (CPG) activation and corresponding locomotor movement generation in completely paraplegic animals. Co-administration orally (by gavage) of buspirone, levodopa and carbidopa was found to dose-dependently induce episodes of steady weight-bearing stepping in low-thoracic (Th9/10) spinal cord-transected (Tx) mice (with no other form of assistance or training).

Non-assisted treadmill training does not improve motor recovery and body composition in spinal cord-transected mice.

Study Design: Experiments in a mouse model of complete paraplegia.

Objectives: To evaluate the effect of non-assisted treadmill training on motor recovery and body composition in completely spinal cord-transected mice.

Settings: Laval University Medical Center, Neuroscience Unit, Quebec City, Quebec, Canada.

Specific role of dopamine D1 receptors in spinal network activation and rhythmic movement induction in vertebrates.

Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species.

Role of spinal 5-HT2 receptor subtypes in quipazine-induced hindlimb movements after a low-thoracic spinal cord transection.

A role of serotonin receptors (5-HTRs) in spinal rhythmogenesis has been proposed several years ago based mainly upon data showing that bath-applied 5-HT could elicit locomotor-like rhythms in in vitro isolated spinal cord preparations. Such a role was partially confirmed in vivo after revealing that systemically administered 5-HTR(2) agonists, such as quipazine, could induce some locomotor-like movements (LM) in completely spinal cord-transected (Tx) rodents. However, given the limited binding selectivity of currently available 5-HTR(2) agonists, it has remained difficult to determine clearly if one receptor subtype is specifically associated with LM induction.

Tail pinching-induced hindlimb movements are suppressed by clonidine in spinal cord injured mice.

Experiments in completely spinal cord transected (Tx) cats have provided compelling evidence that clonidine combined with tail stimulation can promote locomotor function recovery. However, clonidine has generally failed to induce locomotor activity in other comparable animal models suggesting the existence of species- or condition-specific effects. This study aimed at investigating the effects of clonidine administered (0.

Effects of spinal alpha(2)-adrenoceptor and I(1)-imidazoline receptor activation on hindlimb movement induction in spinal cord-injured mice.

A partial recovery of locomotor functions has been shown in spinal cord-transected (Tx) cats after regular treadmill training and repeated administration of clonidine, an alpha(2)-adrenoreceptor agonist. However, clonidine has generally failed to show prolocomotor effects in other models (e.g.

Abnormal IFN-gamma-dependent immunoproteasome modulation by Trypanosoma cruzi-infected macrophages.

Proteasomes are the main producers of Ag loaded onto MHC class I molecules. Following IFN-gamma stimulation however, the constitutive subunits of the proteasome are replaced by the immunosubunits low molecular weight protein 2 (LMP2), multicatalytic endopeptidase complex-like 1 and low molecular weight protein 7 (LMP7), which generally heighten the immunogenecity of proteasome generated epitopes. Given that Trypanosoma cruzi, the aetiological agent of Chagas' disease, elicits a T(helper)1 response from its host if the infection is to be contained, the aim of this study was to verify whether this parasite modulates J774 and B10R mouse macrophage (MuPhi) immunoproteasome subunit and MHC class I expressions and, if so, identify the mechanism(s) responsible for that modulation.

Blockade of antimicrobial proteins S100A8 and S100A9 inhibits phagocyte migration to the alveoli in streptococcal pneumonia.

We investigated the roles of the potent, chemotactic antimicrobial proteins S100A8, S100A9, and S100A8/A9 in leukocyte migration in a model of streptococcal pneumonia. We first observed differential secretion of S100A8, S100A9, and S100A8/A9 that preceded neutrophil recruitment. This is partially explained by the expression of S100A8 and S100A9 proteins by pneumocytes in the early phase of Streptococcus pneumoniae infection.

A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men.

Unlabelled: Using QCT, we made a longitudinal, population-based assessment of rates of bone loss over life at the distal radius, distal tibia, and lumbar spine. Cortical bone loss began in perimenopause in women and later in life in men. In contrast, trabecular bone loss began in young adulthood in both sexes.

Early changes in deep vein diameter and biochemical markers associated with thrombi formation after spinal cord injury in mice.

Spinal cord injury (SCI) is associated with the development of deep venous thrombosis (DVT) in the lower limbs and, hence, with rapidly increasing risks of cardiovascular and pulmonary complications soon after trauma. However, specific mechanisms underlying DVT formation following SCI are poorly understood. Here, we studied in mice, employing in vivo confocal microscopy, changes in deep vein size over 4 weeks after spinal cord transection (Tx).

Structural determinants of vertebral fracture risk.

Unlabelled: Vertebral fractures are more strongly associated with specific bone density, structure, and strength parameters than with areal BMD, but all of these variables are correlated.

Introduction: It is unclear whether the association of areal BMD (aBMD) with vertebral fracture risk depends on bone density per se, bone macro- or microstructure, overall bone strength, or spine load/bone strength ratios.

Materials And Methods: From an age-stratified sample of Rochester, MN, women, we identified 40 with a clinically diagnosed vertebral fracture (confirmed semiquantitatively) caused by moderate trauma (cases; mean age, 78.

The transesophageal Doppler and hemodynamic effects of epidural anesthesia in infants anesthetized with sevoflurane and sufentanil.

Background: It is thought that pediatric epidural anesthesia (EA) provides hemodynamic stability in children. However, when compared with information relating to adults, little is known about the hemodynamic effects of epidural EA on cardiac output (CO) in infants.

Methods: Using transesophageal Doppler to monitor CO, we prospectively studied 14 infants <10 kg who were scheduled for abdominal surgery.

Hormonal and immunological changes in mice after spinal cord injury.

Spinal cord injury (SCI) is associated with immune deficiencies and life-threatening infections. However, the specific mechanisms underlying this pathological condition remain unclear. In recent years, increasing evidence has suggested that anabolic hormones may be involved in immunological complications.

Does reduced skeletal loading account for age-related bone loss?

Unlabelled: A leading theory suggests that decreasing activity and muscle mass is the main cause of age-related bone loss. However, in a population-based study of 375 women and 325 men (age, 21-97 years), we failed to find a close correspondence between these variables and changes in bone strength with aging.

Introduction: It has been suggested that bone strength is homeostatically adapted to habitual skeletal loading conditions and that bone loss could, therefore, result simply from age-related reductions in physical activity and muscle mass, but this notion has not been explored in detail.

Age- and sex-specific differences in the factor of risk for vertebral fracture: a population-based study using QCT.

Unlabelled: We used QCT scans obtained in 687 men and women, 21-97 years of age, to estimate the factor of risk for vertebral fracture, Phi(vert), defined as the ratio of spinal loading to vertebral strength. With age, vertebral strength declined and Phi(vert) increased significantly more in women than men. Age- and sex-specific differences in Phi(vert) closely resembled previously reported vertebral fracture incidence.