Role of the lesion scar in the response to damage and repair of the central nervous system

Traumatic damage to the central nervous system (CNS) destroys the blood-brain barrier (BBB) and provokes the invasion of hematogenous cells into the neural tissue. Invading leukocytes, macrophages and lymphocytes secrete various cytokines that induce an inflammatory reaction in the injured CNS and result in local neural degeneration, formation of a cystic cavity and activation of glial cells around the lesion site. As a consequence of these processes, two types of scarring tissue are formed in the lesion site. One is a glial scar that consists in reactive astrocytes, reactive microglia and glial precursor cells. The other is a fibrotic scar formed by fibroblasts, which have invaded the lesion site from adjacent meningeal and perivascular cells. At the interface, the reactive astrocytes and the fibroblasts interact to form an organized tissue, the glia limitans. The astrocytic reaction has a protective role by reconstituting the BBB, preventing neuronal degeneration and limiting the spread of damage. While much attention has been paid to the inhibitory effects of the astrocytic component of the scars on axon regeneration, this review will cover a number of recent studies in which manipulations of the fibroblastic component of the scar by reagents, such as blockers of collagen synthesis have been found to be beneficial for axon regeneration. To what extent these changes in the fibroblasts act via subsequent downstream actions on the astrocytes remains for future investigation

Single-nucleotide polymorphisms in CCL2 gene are not associated with susceptibility to systemic sclerosis

Objective. To validate the reported association between CC chemokine ligand 2 (CCL2) –2518 G single nucleotide polymorphism and systemic sclerosis (SSc) in a much larger cohort of patients. We also performed subgroup analysis to test the hypothesis that CCL2 variants predispose to specific disease phenotypes. Methods. Ninety-four Caucasian patients with SSc and 102 matched controls were genotyped by sequence-specific primers-polymerase chain reaction (SSP-PCR) methodology. Results. Six biallelic single-nucleotide polymorphisms (SNP) were investigated (3 in the promoter region, 2 in the exon-coding sequence, and 1 in the 3 untranslated region), in addition to the known functional –2518 (A/G) variant. Six major haplotypes were constructed across all 7 SNP positions. No significant differences in genotype, allele, or haplotype frequency were observed between patients and controls or within disease subgroups. Conclusion. Genetic polymorphisms within CCL2 gene are associated with susceptibility neither to SSc nor to specific disease phenotypes

Mechanisms of vascular damage in systemic sclerosis

Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature

Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury

Yoo M, Khaled M, Gibbs KM, et al. Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury. Plos One. 2013;8(3): e57415.Bacterial chondroitinase ABC (ChaseABC) has been used to remove the inhibitory chondroitin sulfate chains from chondroitin sulfate proteoglycans to improve regeneration after rodent spinal cord injury. We hypothesized that the mammalian enzyme arylsulfatase B (ARSB) would also enhance recovery after mouse spinal cord injury. Application of the mammalian enzyme would be an attractive alternative to ChaseABC because of its more robust chemical stability and reduced immunogenicity. A one-time injection of human ARSB into injured mouse spinal cord eliminated immunoreactivity for chondroitin sulfates within five days, and up to 9 weeks after injury. After a moderate spinal cord injury, we observed improvements of locomotor recovery assessed by the Basso Mouse Scale (BMS) in ARSB treated mice, compared to the buffer-treated control group, at 6 weeks after injection. After a severe spinal cord injury, mice injected with equivalent units of ARSB or ChaseABC improved similarly and both groups achieved significantly more locomotor recovery than the buffer-treated control mice. Serotonin and tyrosine hydroxylase immunoreactive axons were more extensively present in mouse spinal cords treated with ARSB and ChaseABC, and the immunoreactive axons penetrated further beyond the injury site in ARSB or ChaseABC treated mice than in control mice. These results indicate that mammalian ARSB improves functional recovery after CNS injury. The structural/molecular mechanisms underlying the observed functional improvement remain to be elucidated

New evidence for the Mousterian and Gravettian at Rio Secco Cave, Italy

The dearth of evidence for late Neanderthals in Europe reduces our ability to understand the demise of their species and the impact of the biological and cultural changes that resulted from the spread of anatomically modern humans. In this light, a recently investigated cave in the northern Adriatic region at the border between the Italian Alps and the Great Adriatic Plain provides useful data about the last Neanderthals between 46·0 and 42·1 ky cal b.p. Their subsistence is inferred from zooarchaeological remains and patterns in Middle Palaeolithic lithic technology. Unexpected evidence of the ephemeral use of the cave during the early Upper Palaeolithic Gravettian period shows a change in lithic technology