The relationship between low survival and acute increase of tumor necrosis factor α expression in the lung in a rat model of asphyxial cardiac arrest.

Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.

Changes in histopathology and tumor necrosis factor-α levels in the hearts of rats following asphyxial cardiac arrest.

OBJECTIVE: Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have return of spontaneous circulation (ROSC) after CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during the post CA syndrome. METHODS: We induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate of these rats during the post resuscitation phase. RESULTS: Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA and afterwards, histopathological changes were not significant. In addition, levels of tumor necrosis factor-α immunoreactivity gradually increased after CA. CONCLUSION: The survival rate of rats 2 days post CA was very low, even though histopathological and inflammatory changes in the heart were not pronounced in the early stage following CA.

Transient Cerebral Ischemia Alters GSK-3ß and p-GSK-3ß Immunoreactivity in Pyramidal Neurons and Induces p-GSK-3ß Expression in Astrocytes in the Gerbil Hippocampal CA1 Area.

Glycogen synthase kinase 3ß (GSK-3ß) is a key downstream protein in the PI3K/Akt pathway. Phosphorylation of serine 9 of GSK-3ß (GSK-3ß activity inhibition) promotes cell survival. In this study, we examined changes in expressions of GSK-3ß and phosphorylation of GSK-3ß (p-GSK-3ß) in the gerbil hippocampal CA1 area after 5 min of transient cerebral ischemia. GSK-3ß immunoreactivity in the CA1 area was increased in pyramidal cells at 6 h after ischemia-reperfusion. It was decreased in CA1 pyramidal cells from 12 h after ischemia-reperfusion, and hardly detected in the CA1 pyramidal cells at 5 days after ischemia-reperfusion. p-GSK-3ß immunoreactivity was slightly decreased in CA1 pyramidal cells at 6 and 12 h after ischemia-reperfusion. It was significantly increased in these cells at 1 and 2 days after ischemia-reperfusion. Five days after ischemia-reperfusion, p-GSK-3ß immunoreactivity was hardly found in CA1 pyramidal cells. However, p-GSK-3ß immunoreactivity was strongly expressed in astrocytes primarily distributed in strata oriens and radiatum. In conclusion, GSK-3ß and p-GSK-3ß were significantly changed in pyramidal cells and/or astrocytes in the gerbil hippocampal CA1 area following 5 min of transient cerebral ischemia. This finding indicates that GSK-3ß and p-GSK-3ß are closely related to delayed neuronal death.

What factors determine the need for lumbar puncture in patients with fever and headache?

INTRODUCTION: We performed this study to find clinical features and laboratory parameters that could facilitate the process of selecting patients who should receive lumbar punctures from among those who present with headache and fever. METHODS: We selected patients aged ≥ 16 years who presented to and received lumbar puncture in the emergency department of Kangwon National University Hospital, South Korea, between 2011 and 2013. Patients who received lumbar punctures were divided into two groups - those who were diagnosed with viral meningitis and those who were not. We compared the clinical features and laboratory data between the two groups. Key indices were then used to develop a scoring system to diagnose viral meningitis in patients and identify those who should receive lumbar punctures. RESULTS: Among the patients who were included in the study, 42 had viral meningitis and 96 did not. The variables of C-reactive protein level ≤ 1.291 mg/dL, neck stiffness and vomiting were assigned 3 points, 2 points and 1 point, respectively, in the scoring system. Overall scores ≥ 4 yielded a positive likelihood ratio of 7.79 (sensitivity 0.600, specificity 0.923), while negative likelihood ratio decreased to less than 0.1 (0.072) for overall scores < 3. CONCLUSION: Using the proposed scoring system, we were able to determine the likelihood of viral meningitis in patients presenting with fever and headache, and to successfully identify those who should receive lumbar punctures.

Long-term changes in neuronal degeneration and microglial activation in the hippocampal CA1 region after experimental transient cerebral ischemic damage.

Delayed neuronal death following transient cerebral ischemia is mixed with apoptosis and necrosis, and the activation of microglia are activated after the ischemic insult. In the present study, we examined the long-term changes in neuronal degeneration and microglial activation in the gerbil hippocampal CA1 region after 5min of transient cerebral ischemia using specific markers for neuronal damage and microliosis. Transient ischemia-induced neuronal death was shown in CA1 pyramidal cells 4days after ischemia/reperfusion (I/R). However, neuronal degeneration of the pyramidal cells were observed up to 45days in the CA1 region after I/R. Microglial activation was also observed in the CA1 region after I/R. Isolectin B4- (IB4) immunoreactive ((+)) microglia appeared in the CA1 region 4days after I/R. On the other hand, ionized calcium-binding adapter molecule 1 (Iba-1)(+) microglia was markedly increased after I/R, and peaked at 15days after I/R. Thereafter, Iba-1 immunoreactivity was decreased with time-dependant manner in the ischemic CA1 region. These results indicate that neuronal degeneration of CA1 pyramidal cells may last about 45days in the CA1 region after ischemic damage, and microglial activation may be diverse according to their function, such as phagocytosis, after I/R.

Rosiglitazone, an agonist of peroxisome proliferator-activated receptor gamma, decreases immunoreactivity of markers for cell proliferation and neuronal differentiation in the mouse hippocampus.

In the present study, we investigated the regulating effects of rosiglitazone (RSG), a synthetic agonist of peroxisome proliferator-activated receptor gamma, treatment for 28days on the cell proliferation and neuronal differentiation in the mouse hippocampal dentate gyrus by 5-bromo-2'-deoxyuridine (BrdU), Ki67 and doublecortin (DCX) immunohistochemistry. These markers were detected in the subgranular zone (SGZ) of the dentate gyrus in vehicle- and RSG-treated groups. In the RSG-treated group, the number of BrdU-, Ki67- and DCX-immunoreactive cells was significantly decreased compared to those in the vehicle-treated group. In addition, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor levels were significantly decreased in the dentate gyrus of the RSG-treated groups compared to the vehicle-treated group. These results indicate that RSG treatment decreases immunoreactivities of markers for cell proliferation and neuronal differentiation and levels of neurotrophic factors in the SGZ of the hippocampal dentate gyrus.

Neuronal degeneration and microglial activation in the ischemic dentate gyrus of the gerbil.

In the present study, we investigated the time-course changes of neuronal degeneration and microglial activation in the gerbil dentate gyrus after transient cerebral ischemia using Fluoro-Jade B histofluorescence staining and immunohistochemistry for Iba-1. Fluoro-Jade B positive cells were observed from 6 hr and markedly increased 1 day after ischemia/reperfusion. Iba-1-immunoreactive microglia were increased and hypertrophied at early time, and Iba-1 immunoreactivity was highest at 2 days after ischemia/reperfusion. These results may be direct evidence on neuronal degeneration and microglial activation in the gerbil dentate gyrus after ischemia/reperfusion.