Microglia are essential for CNS homeostasis and innate neuroimmune function, and play important roles in neurodegeneration and brain aging. Here we present gene expression profiles of purified microglia isolated at autopsy from the parietal cortex of 39 human subjects with intact cognition. Overall, genes expressed by human microglia were similar to those in mouse, including established microglial genes CX3CR1, P2RY12 and ITGAM (CD11B). However, a number of immune genes, not identified as part of the mouse microglial signature, were abundantly expressed in human microglia, including TLR, Fcγ and SIGLEC receptors, as well as TAL1 and IFI16, regulators of proliferation and cell cycle. Age-associated changes in human microglia were enriched for genes involved in cell adhesion, axonal guidance, cell surface receptor expression and actin (dis)assembly. Limited overlap was observed in microglial genes regulated during aging between mice and humans, indicating that human and mouse microglia age differently.
ChAc is a neurodegenerative disease with distinct cortical neurodegeneration. The hypertrophy of the peripheral neuropil space of minicolumns with coarse vertical striation was characteristic of ChAc. The role of astroglia in the pathogenesis of this disorder remains to be elucidated.
Heparinization is a routine procedure during angioplasty; however, its consequences on the late vascular response to a severe injury are unclear. The authors' objective was to explore the effect of a single heparin bolus at the time of a severe vascular injury on late intimal proliferation and neointimal thickening. The iliac artery of 57 normolipemic rabbits was overdistended with a balloon catheter. Heparin (250 IU/kg i.v.) was given to 29 rabbits ten minutes before angioplasty, whereas 28 rabbits served as untreated controls. Neointimal thickening was prominent at fourteen days after injury and reached near-maximal values at day 28. The intimal/medial area ratio was reduced by an average 28.3% with heparin (at day 28: 2.19 +/- 0.51 vs 1.57 +/- 0.59, control vs heparin, P = 0.02). Neointimal cells stained positively for HHF-35 antibody, directed against smooth muscle cell antigens. Neointimal proliferation, quantified through the number of cell nuclei peroxidase-stained for PCNA/cyclin antigen, was significantly decreased by 43% and 49% with heparin, respectively, at days 7 and 14 after injury. These data suggest that early exposure even to low doses of heparin accounts for much of its inhibitory effect in vascular response to injury; such an effect might prove important in interpreting results of human trials of interventions against restenosis.
The employment of photoablative effect on coronary artery angioplasty has been a new exciting field as a treatment option. Guided by good results in the literature, our group decided to study the laser/tissue interaction on carotid arteries with the intent of a less invasive treatment of intracranial and extracranial obstmcted disease in vascular neurosurgery. We studied human carotid arteries from ten male autopsy specimens with an average age of 53 years (34-37 years old) which a total of 22 laser applications were perfonned. Using the same repetition rate and energy, 20 Hz and 30 mJ, we compared the effect of the laser energy on 'normal and "pathologic areas of the carotid arteries. The pathologic specimens, presenting calcified and non-calcified plaques, the same as the macroscopical "normal" specimens, were submitted to the energy of the Excimer Laser with 308 nm wavelength. The laser beam was delivered perpendicularly through continuous flushing of saline on the targeted artery wall varying from 200 to 4000 pulses.Histological studies were done and statistical analysis was performed. The results showed that the depth of penetration varied from 1 13 urn to 1200 urn, with a width of the lesion ranging from 150 um -1500 urn. In our study we found that the range between non-effective and destructive effect caused by the laser was around 400 pulses. We encountered minimal degree of carbonization while lasenng on calcified plaques. We concluded that Excimer laser is a feasible and secure tool to prevent thermical complications of laser treatment, which will allow neurosurgeons in the future athermic laser angioplasty. Progress in this field must rely on further in vitro and in vivo research, before it can be clinically applied as well as improvements in delivery systems.
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