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Background Polynitroxylated PEGylated hemoglobin (PNPH, aka SanFlow) possesses superoxide dismutase/catalase mimetic activities that may directly protect the brain from oxidative stress. Stabilization of PNPH with bound carbon monoxide prevents methemoglobin formation during storage and permits it to serve as a carbon monoxide donor. We determined whether small volume transfusion of hyperoncotic PNPH is neuroprotective in a polytrauma model of traumatic brain injury (TBI) plus hemorrhagic shock. Guinea pigs were used because, like humans, they do not synthesize their own ascorbic acid, which is important in reducing methemoglobin. Results TBI was produced by controlled cortical impact and was followed by 20 mL/kg hemorrhage to a mean arterial pressure (MAP) of 40 mmHg. At 90 min, animals were resuscitated with 20 mL/kg lactated Ringer’s solution or 10 mL/kg PNPH. Resuscitation with PNPH significantly augmented the early recovery of MAP after hemorrhagic shock by 10–18 mmHg; whole blood methemoglobin was only 1% higher and carboxyhemoglobin was 2% higher. At 9 days of recovery, unbiased stereology analysis revealed that, compared to animals resuscitated with lactated Ringer’s solution, those treated with PNPH had significantly more viable neurons in the hippocampus CA1 + 2 region (59 ± 10% versus 87 ± 18% of sham and naïve mean value) and in the dentate gyrus (70 ± 21% versus 96 ± 24%; n = 12 per group). Conclusion PNPH may serve as a small-volume resuscitation fluid for polytrauma involving TBI and hemorrhagic shock. The neuroprotection afforded by PNPH seen in other species was sustained in a species without endogenous ascorbic acid synthesis, thereby supporting potential translatability for human use.

Primary blast injury can result in depression-like behavior in the long-term. However, the effects of the selective serotonin reuptake inhibitor (SSRI) on the depression induced by mild blast traumatic brain injury (bTBI) in the long-term remain unclear. We generated a mouse model of mild bTBI using laser-induced shock wave (LISW) and administered an SSRI to mice by oral gavage for 14 days after LISW exposure. This study aimed to investigate the mechanisms of SSRI-mediated alleviation of depression-like behavior induced by mild bTBI. Animals were divided into three groups: sham, LISW-Vehicle, and LISW-SSRI. LISW was applied to the head of anesthetized mice at 0.5 J/cm2. Twenty-eight days after the LISW, mice in the LISW-SSRI group exhibited reduced depression-like behavior, a significant increase in the number of cells co-stained for 5-bromo-2'-deoxyuridine (Brd-U) and doublecortin (DCX) in the dentate gyrus (DG) as well as increased brain-derived neurotrophic factor (BDNF) and serotonin levels in the hippocampus compared to the sham and LISW-Vehicle groups. Additionally, levels of phosphorylated cAMP response element binding protein (pCREB) in the DG were significantly decreased in the LISW-Vehicle group compared to that in the sham group. Importantly, pCREB levels were not significantly different between LISW-SSRI and sham groups suggesting that SSRI treatment may limit the downregulation of pCREB induced by mild bTBI. In conclusion, recovery from depression-like behavior after mild bTBI may be mediated by hippocampal neurogenesis induced by increased BDNF and serotonin levels as well as the inhibition of pCREB downregulation in the hippocampus.

Case We describe a rare case of antibiotic-associated fulminant pseudomembranous enterocolitis caused by Klebsiella oxytoca. A 79-year-old man with a history of antibiotic therapy was admitted to our emergency department, complaining of consciousness disturbance. Initially, we suspected septic shock and diabetic ketoacidosis caused by intestinal infection. Although we administered sufficient extracellular fluid, his blood pressure was not elevated and his abdomen gradually swelled. Outcome The patient died of shock and abdominal compartment syndrome. Autopsy revealed widespread jejunal necrosis in conjunction with colitis, suggesting fulminant pseudomembranous enterocolitis caused by K. oxytoca infection. Conclusion As the clinical features of pseudomembranous enterocolitis caused by K. oxytoca resemble the features of colitis caused by Clostridium difficile, conservative therapy is applied first. However, fulminant pseudomembranous enterocolitis is a lethal disease, necessitating early operation for resection of the necrotic lesion. This report highlights the need for better surgical criteria at an early stage.

The incidence of traumatic brain injury (TBI) in elderly patients is increasing. We retrospectively investigated the poor prognostic factors at discharge in elderly patients aged 75 years or older admitted to hospital with mild TBI. We continuously enrolled 83 patients aged 75 years or older with mild TBI, in a private general Japanese hospital. The Glasgow Coma Scale scores on admission were within the range of 13-15. Patients with good recovery or moderate disability were included in the "good outcome" group, and those with severe disability, in a persistent vegetative state, or who died were included in the "poor outcome" group. We performed statistical analyses using 8 parameters. We conducted a univariate analysis on each item. Next, we conducted a logistic regression analysis on variables where the p 0.20 in the univariate analysis. Elderly patients had a poor prognosis when they had dementia (odds ratio [OR]: 20.357, 95% confidence interval [CI]: 2.075-199.683, p = 0.010), cancer (OR: 14.005, 95% CI: 1.262-154.444, p = 0.032), or a history of antithrombotic therapy before admission (OR: 6.673, 95% CI: 1.072-41.526, p = 0.042). When elderly patients aged 75 years or older with mild TBI have the 3 poor prognostic factors of dementia, cancer, or a history of antithrombotic therapy, their outcomes might be worse compared to other elderly patients. Elderly patients who have these factors should be carefully managed.

Background When symptoms of cerebral infarction are recognized in a patient, he or she should be transported to a hospital and should be started on the appropriate treatments. The effectiveness of delayed treatment of cerebral infarction with respect to the initial diagnosis or perception of the disease is still unclear. Methods We retrospectively investigated whether the functional outcomes would improve if patients with cerebral infarction were transported to the hospital with minimum delay. One-hundred twenty-two patients who were transported to Mishuku Hospital from January 2012 to August 2015 were included. We conducted multiple regression analyses. The criterion variable included the BI at discharge, and the explanatory variables were age, sex, days of hospital stay, the Barthel Index (BI) on admission, time from symptom onset to hospital arrival, time from emergency medical service perception to hospital arrival, recombinant tissue plasminogen activator (rt-PA) treatment, and the occluded artery type. Results In all 122 cases, the BI at the time of discharge was not related to onset time ( P = .453) but was significantly related to perception time ( P = .026). BI scores at discharge were high for young patients ( P = .002) and for patients with short hospital stays ( P .001). In the rt-PA group (52 cases), BI scores at discharge were also high when the perception time was short ( P = .036). Conclusions A short interval between perception and hospital arrival improves the functional outcomes for patients with cerebral infarction. Thus, patients with cerebral infarctions must be treated with minimal delay after diagnosis of the condition.

Blast-induced mild traumatic brain injury (mild bTBI) has been a frequent battlefield injury in soldiers during the conflicts in Iraq and Afghanistan. Understanding the pathophysiology and determining effective treatments for mild bTBI has become an international problem in the field of neurotrauma research. Contributing to this problem is a lack of an experimental model that accurately mimics the characteristics of mild bTBI. To date, the "mild'' versions of common experimental models of TBI have simply been less severe degrees of traumatic injury; these animals do not necessarily exhibit the clinical characteristics of mild bTBI seen in humans. Therefore, our first objective was to develop a highly controlled mouse model of bTBI using laser-induced shockwaves (LISWs). We established the parameters necessary to cause a reproducible injury of very mild severity, the most important feature seen in clinical practice. We defined very mild bTBI as having no traumatic change on the head visible to the naked eye after the insult was applied using very mild shockwaves to the heads of mice. Our very mild bTBI mouse model exhibited neurobehavioral changes in the chronic phase, such as cognitive impairment and depression-like behavior. We also observed an increase in 5-bromo-2'-deoxyuridine-positive, proliferating cells in the dentate gyrus during the acute phase and a subsequent decrease during the chronic phase. This model appears to be an accurate representation of the damage occurring in actual mild bTBI patients. We also found that an increase in cell proliferation in the dentate gyrus during the acute phase is the most prominent feature after a TBI.

Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater. Recently, the possibility that IgG4-related sclerosing disease may underlie some cases of intracranial hypertrophic pachymeningitis has been suggested. We herein report the tenth case of IgG4-related intracranial hypertrophic pachymeningitis and review the previous literature. A 45-year-old male presented with left-sided focal seizures with generalization. Magnetic resonance imaging (MRI) revealed a diffuse thickening and enhancement of the right convexity dura matter and falx with focal nodularity. The surgically resected specimens exhibited the proliferation of fibroblast-like spindle cells and an infiltration of mononuclear cells, including predominantly plasma cells. The ratio of IgG4-positive plasma cells to the overall IgG-positive cells was 45% in the area containing the highest infiltration of plasma cells. On the basis of the above findings, IgG4-related sclerosing disease arising from the dura mater was suspected. IgG4-related sclerosing disease should be added to the pachymeningitis spectrum.

True posterior communicating artery (PCoA) aneurysm is an aneurysm that originates from the PCoA, and large or giant true PCoA aneurysms are rare. We report a case of a large true PCoA aneurysm successfully clipped after anterior clinoidectomy and discuss the diagnostic pitfalls associated with this rare clinical entity.