Less neurogenesis and inflammation in the immature than in the juvenile brain after cerebral hypoxia-ischemia.

The effects of hypoxia-ischemia (HI) on proliferation and differentiation in the immature (postnatal day 9) and juvenile (postnatal day 21) mouse hippocampus were investigated by injecting bromodeoxyuridine (50 mg/kg) daily for 7 days after the insult and evaluating the labeling 5 weeks after HI. Phenotypic differentiation was evaluated using NeuN, Iba1, APC, and S100beta as markers of neurons, microglia, oligodendrocytes, and astrocytes, respectively. The basal proliferation, in particular neurogenesis, was higher in the immature than in the juvenile hippocampus. Hypoxia-ischemia did not increase neurogenesis significantly in the immature dentate gyrus (DG), but it increased several-fold in the juvenile brain, reaching the same level as in the normal, noninjured immature brain. This suggests that the immature hippocampus is already working at the top of its proliferative capacity and that even though basal neurogenesis decreased with age, the injury-induced generation of new neurons in the juvenile hippocampus could not increase beyond the basal level of the immature brain. Generation of glial cells of all three types after HI was significantly more pronounced in the cornu ammonis of the hippocampus region of the juvenile hippocampus. In the DG, only microglia production was greater in the juvenile brain. Increased microglia proliferation correlated with increased levels of the proinflammatory cytokines MCP-1 and IL-18 3 days after HI, indicating that the inflammatory response is stronger in the juvenile hippocampus. In summary, contrary to what has been generally assumed, our results indicate that the juvenile brain has a greater capacity for neurogenesis after injury than the immature brain.     

Decreased neurogenesis after cholinergic forebrain lesion in the adult rat

Adult neurogenesis has been shown to be regulated by a multitude of extracellular cues, including hormones, growth factors, and neurotransmitters. The cholinergic system of the basal forebrain is one of the key transmitter systems for learning and memory. Because adult neurogenesis has been implicated in cognitive performance, the present work aims at defining the role of cholinergic input for adult neurogenesis by using an immunotoxic lesion approach. The immunotoxin 192IgG-saporin was infused into the lateral ventricle of adult rats to selectively lesion cholinergic neurons of the cholinergic basal forebrain (CBF), which project to the two main regions of adult neurogenesis: the dentate gyrus and the olfactory bulb. Five weeks after lesioning, neurogenesis, defined by the number of cells colocalized for bromodeoxyuridine (BrdU) and the neuronal nuclei marker NeuN, declined significantly in the granule cell layers of the dentate gyrus and olfactory bulb. Furthermore, immunotoxic lesions to the CBF led to increased numbers of apoptotic cells specifically in the subgranular zone, the progenitor region of the dentate gyrus, and within the periglomerular layer of the olfactory bulb. We propose that the cholinergic system plays a survival-promoting role for neuronal progenitors and immature neurons within regions of adult neurogenesis, similar to effects observed previously during brain development. As a working hypothesis, neuronal loss within the CBF system leads not only to cognitive deficits but may also alter on a cellular level the functionality of the dentate gyrus, which in turn may aggravate cognitive deficits.     

Clinical Results of Flexor Tendon Repair in Zone II Using a six Strand Double Loop Technique

The purpose of this study is to report the clinical results after repair of flexor tendon zone II injuries utilizing a 6-strand double-loop technique and early post-operative active rehabilitation. We retrospectively reviewed 22 patients involving 51 cases with zone II flexor tendon repair using a six strand double loop technique from September 1996 to December 2012. Most common mechanism of injuries was sharp lacerations (86.5 %). Tendon injuries occurred equally in manual and non-manual workers and were work-related in 33 % of the cases. The Strickland score for active range of motion (ROM) postoperatively was excellent and good in the majority of the cases (81 %). The rupture rate was 1.9 %. The six strand double loop technique for Zone II flexor tendon repair leads to good and excellent motion in the majority of patients and low re- rupture rate. It is clinically effective and allows for early postoperative active rehabilitation.     

Acute exposure of mice to hydrochloric acid leads to the development of chronic lung injury and pulmonary fibrosis

Objective: Accidental exposure to hydrochloric acid (HCl) is associated with acute lung injury in humans, development of long-term chronic airway obstruction, and fibrosis. However, the mechanisms responsible for the progression to pulmonary fibrosis remain unclear. We utilized a mouse model of progressive lung injury from a single exposure to HCl to investigate the effects of HCl on the lower respiratory tract.

Materials and methods: HCl (0.05–0.3?N) or saline was injected intratracheally into male C57Bl/6J mice. At 1, 4, 10 and 30 days post instillation, bronchoalveolar lavage fluid (BALF) and lung tissues were collected and examined for multiple outcomes.

Results and discussion: We observed an early inflammatory response and a late mild inflammation present even at 30?d post HCl exposure. Mice treated with HCl exhibited higher total leukocyte and protein levels in the BALF compared to the vehicle group. This was characterized by increased number of neutrophils, monocytes, and lymphocytes as well as pro-inflammatory cytokines during the first 4?d of injury. The late inflammatory response exhibited a predominant presence of mononuclear cells, increased permeability to protein, and higher levels of the pro-fibrotic mediator TGFβ. Pro-fibrotic protein biomarkers, phosphorylated ERK, and HSP90, were also overexpressed at 10 and 30?d following HCl exposure. In vivo lung function measurements demonstrated lung dysfunction and chronic lung injury associated with increased lung hydroxyproline content and increased expression of extracellular matrix (ECM) proteins. The acute inflammation and severity of fibrosis increased in HCl-concentration dependent manner.

Conclusions: Our findings suggest that the initial inflammatory response and pro-fibrotic biomarker upregulation may be linked to the progression of pulmonary fibrosis and airway dysfunction and may represent valuable therapeutic targets.     

Multicenter analytical performance evaluation of the Elecsys proBNP assay.

The purpose of this multicenter study was to evaluate the technical performance of the automated Elecsys proBNP (brain natriuretic peptide) assay, which is indicated as an aid in the diagnosis of individuals suspected of having congestive heart failure. The Elecsys proBNP assay is an electrochemiluminescent immunoassay employing two polyclonal NT-proBNP-specific antibodies in a sandwich test format. The study was performed on the three Elecsys analyzers (E 1010, E 2010, and E 170) at eight different sites world-wide. Within- and total precision were < or = 3%, with total precision slightly higher on the Elecsys E 170 instrument with multiple modules. Reproducibility among sites and platforms was < 5%. Precision at particularly low NT-proBNP concentrations was assessed down to approximately 25 pg/ml with CVs of 12.6% at 29.2 pg/ml and 9.6% at 38.5 pg/ml for the Elecsys 1010/2010 and E 170, respectively. Linearity was evaluated up to 25,000 pg/ml with a sample-based non-linear response observed with recoveries of < 90% for proBNP concentrations < 10,000 pg/ml. Slopes ranged between 0.92 and 1.02 and intercepts from -5.3 to 10.4 pg/ml (r > or = 0.998) among the three types of analyzers. Slopes were 4.95 and 4.53 in comparison to the Biosite Triage and Shionogi BNP assays. There was no assay interference, and no effect of barrier gels, tube composition, or freeze-thaw. NT-proBNP concentrations in EDTA plasma were up to 10% lower than in serum or heparinized plasma and the analyte was stable at 4 degrees C for up to 72 hours (the maximum time tested). There was no circadian rhythm in normal subjects or congestive heart failure patients and there was no effect of drawing position. In summary, the Elecsys proBNP assay exhibits good technical performance and is suitable for use in routine clinical laboratories to aid in the diagnosis of congestive heart failure.