Brain Injury review

This abstract comes from L Eggert and collagues from the Christensen lab at the NICU development team in Salt lake city.

OBJECTIVE: Kernicterus is a rare but devastating condition. The prevention of bilirubin-induced brain injury is based on the detection of infants at risk for developing severe hyperbilirubinemia. In an 18-hospital health system, Intermountain Health Care (IHC), we initiated a program of predischarge bilirubin screening of all neonates and coupled this with a results assessment using a percentile-based nomogram. Data during 2 periods of time, before versus after initiating the program, were compared to assess the effect of the program on significant hyperbilirubinemia and rehospitalization.

METHODS: We conducted a historic cohort study involving all neonates delivered at > or =35 weeks’ gestation, within IHC’s 18-hospital system, during 2 periods of time: March 1, 2001, to December 31, 2002, versus January 1, 2003, to December 31, 2004. A bilirubin screening program, instituted in December 2002, called for a total serum bilirubin or transcutaneous bilirubin measurement to be performed on every neonate either at the recognition of clinical jaundice or before discharge regardless of whether jaundice was observed. For nonjaundiced neonates, the nursery staff was encouraged to obtain the screening total serum bilirubin at the same time they obtained the state-mandated newborn screen for inborn errors of metabolism. Bilirubin values were plotted on an hour-specific nomogram and the corresponding percentile was used to guide evaluation, therapy, and follow-up. This study compared TSB data and readmission data for a 2-year period before versus a 2-year period after implementing the program.

RESULTS: The study involved 101272 neonates: 48789 in period 1 and 52483 in period 2. Before the program, 1 in every 77 neonates born at an IHC hospital had 1 or more serum bilirubin levels >20 mg/dL. After initiating the program, the incidence fell to 1 in 142 and the number of neonates with a level >25 mg/dL fell from 1 in 1522 before to 1 in 4037 after. The rate of hospital readmission with a primary diagnosis of jaundice fell from 0.55% in period 1 to 0.43% in period 2.

CONCLUSIONS: Initiating a program of bilirubin screening in a multihospital health system, coupled with evaluating the results using a percentile-based nomogram, reduced the proportion of neonates with significant hyperbilirubinemia and reduced the rate of hospital readmissions with jaundice.

PMID: 16651290 [PubMed - in process]

This article is from H. Wu and friends at the Jingling hospital within Nanjing University in China. it is published in the European Journal of cardio-throrac surgury.

Objective: Based on the findings that erythropoietin has been proved to be a multiple functional cytokine to attenuate ischemia-reperfusion (I/R) injury in various organs such as brain, heart, and kidney in animals, this experiment was designed to evaluate the effect of pretreatment with recombined human erythropoietin on I/R-induced lung injury. Methods: Left lungs of rats underwent 90min of ischemia and then were reperfused for up to 2h. Animals were randomly divided into three experimental groups as sham group, I/R group, and recombined human erythropoietin +I/R group (a single dose of recombined human erythropoietin was injected intraperitoneally 3000U/kg 24h prior to operation). Lung injury was evaluated according to semi-quantitive analysis of microscopic changes, tissue polymorphonuclear neutrophils (PMNs) accumulation (myeloperoxidase (MPO) activity), and pulmonary microvascular permeability (Evan’s blue dying method). Peripheral arterial and venous blood samples were obtained for blood-gas analysis after 5min occlusion of right lung hilus at the end of reperfusion. The serum concentration of tumor necrosis factor (TNF)-alpha was also measured by the method of enzyme-linked immunosorbent assay.

Results: Histological injury scoring revealed significantly lessened lung alveolus edema and neutrophils infiltration in the recombined human erythropoietin pretreated group compared with I/R group (p<0.05). The recombined human erythropoietin pretreated animals exhibited markedly decreased lung microvascular permeability (p<0.05) and myeloperoxidase activity (p<0.05). Blood-gas analysis demonstrated that the pretreated animals had significantly ameliorated pulmonary oxygenation function (p<0.05). The serum concentration of tumor necrosis factor-alpha in recombined human erythropoietin pretreated group was markedly decreased compared with that of I/R group (p<0.05).

Conclusions: Pretreatment with recombined human erythropoietin appears to attenuate I/R-induced lung injury. This function is partly related with the capacity that recombined human erythropoietin inhibits the accumulation of polymorphonuclear neutrophils in lung tissue and decreases the systematic expression of tumor necrosis factor-alpha.

The pubmed ID is 16675226

This abstract comes from Q Guan and colleagues from the Zhang lab at the Xuzhou Medical College in Taiwan.

Our previous studies and the others have strongly suggested that -Jun N-terminal kinase signaling pathway plays a critical role in ischemic brain injury. Here, we reported that SP600125, a potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal kinase, potently decrease neuronal apoptosis induced by global ischemia/reperfusion in the vulnerable hippocampal CA1 subregion.

As a result, SP600125 diminished the increased phosphorylation of c-Jun and the increased expression of FasL induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. At the same time, through inhibiting phosphorylation of Bcl-2 and the release of Bax from Bcl-2/Bax dimers, SP600125 attenuated Bax translocation to mitochondria and the release of cytochrome c induced by ischemia/reperfusion (I/R). Furthermore, the activation of caspase-3 induced by ischemia/reperfusion was also significantly suppressed by preinfusion of SP600125. Importantly, the same neuropotective effect was showed by administration of SP600125 both before and after ischemia.

Thus, our findings imply that SP600125 can inhibit the activation of-Jun N-terminal kinase signaling pathway and induce neuroprotection against ischemia/reperfusion in rat hippocampal CA1 region via suppressing the extrinsic and intrinsic pathways of apoptosis. Taken together, these results indicate that targeting the c-Jun N-terminal kinase pathway provides a promising therapeutic approach for ischemic brain injury.

The pubmed identifier for this abstract is 16674927. It is in the may 2006 edition of Brain Research.