Long-term immune cell profiling in stroke patients with or without infections.

PURPOSE: Infections are frequent complications in acute ischemic stroke and may be caused by an altered immune response influencing brain damage. We compared long-term immune responses in stroke patients with or without infections during the recovery period by performing a long-term profiling of clinically relevant inflammatory parameters from stroke onset until day 49. MATERIALS AND METHODS: Thirty-four stroke patients were retrospectively included and divided into two groups depending on infection status. Group 1 had no infections (N = 17) and group 2 had post-admission infection (N = 17). The patients were evaluated carefully for infections and evolution of the peripheral inflammatory response. Neutrophils, monocytes, lymphocytes, total leukocytes and C-reactive protein were evaluated in relation to the occurrence and development of infections. In both patient groups, an acute boost in neutrophils and monocytes were observed whereas the opposite was true for lymphocytes. RESULTS: In Group 1, neutrophils and monocytes approached normal levels after 20-30 days, but remained elevated in Group 2. We found an increase in neutrophils (p = 0.01) and leukocytes (p < 0.01) as well as C-reactive protein (p < 0.01) among infected patients. Lymphocytes remained depressed in Group 2, while Group 1 slowly approached baseline levels. In both groups, CRP levels initially increased with a slow return to baseline levels. From day 0 to 49 after stroke, uninfected patients generally experienced a decline in leukocytes, neutrophils and monocytes (all p < 0.05), while no similar changes happened among infected patients. CONCLUSIONS: Our study provides an overview of general immune cell kinetics after stroke related to infection status. Immune cell numbers were severely disturbed for weeks after the insult, independent of infection status, although infected patients achieved the highest cell counts of neutrophils, leukocytes and for C-reactive protein. The sustained depression of lymphocytes, especially and paradoxically among infected patients, warrants future studies into the mechanisms behind this, with potential for future therapies aimed at restoring normal immunity and thereby improving patient outcome.

Quantification of Tau-A in serum after brain injury: a comparison of two analytical platforms, ELISA and electrochemiluminescence immunoassay.

BACKGROUND: Previous studies have indicated the utility of the ADAM10-generated fragment of tau, Tau-A, as marker of neuronal damage. However, the sensitivity of the ELISA-based system was limited. OBJECTIVES: We utilized the extensive dynamic range of electrochemiluminescence compared to colorimetric assessment to improve the sensitivity of the Tau-A assay and investigate Tau-A levels after brain injury. METHODS: We converted the Tau-A competitive ELISA to a competitive electrochemiluminescence-based immunoassay, Tau-A ECLIA, and compared the methods by measuring serum samples in a TBI (n = 40) and a stroke cohort (n = 64). RESULTS: The Tau-A ECLIA was technically robust. Only 1% of the samples was below the detection limit in the ECLIA compared to 10.6% in the ELISA . Tau-A measured in both assays could discriminate between patients with a TBI and non-trauma controls (ELISA: p = 0.0005, ECLIA: p = 0.0002). The increased dynamic range of the Tau-A ECLIA also allowed discrimination between healthy controls from patients with hemorrhagic (p = 0.0172) and severe ischemic stroke (p = 0.0118) respectively, as well as patients with mild ischemic stroke from severe (p = 0.0445). CONCLUSIONS: The Tau-A ECLIA was characterized by dynamic range compared to the ELISA, which facilitated a better separation between the patient groups. Tau-A warrants further investigation as a neuronal injury associated marker.

A dose-response study of nitric oxide synthase inhibition in different vascular beds in man.

BACKGROUND AND OBJECTIVE: Nitric oxide (NO) is an almost ubiquitous messenger molecule and is implicated in several disorders. NG monomethyl L-arginine ( L-NMMA:546C88) is an inhibitor of all three NO synthases (NOS), the enzymes that catalyse the production of NO. The present study was performed to evaluate the dose-response relation of L-NMMA to improve the design and interpretation of studies in migraine sufferers and other diseases. METHODS: In a double-blind, placebo-controlled, cross-over design, six healthy volunteers were randomised to receive three different doses of L-NMMA (0.3 mg/kg, 1 mg/kg, 3 mg/kg) or placebo (5% dextrose) intravenously (iv) over 5 min on four different days. On a fifth study day, in an open design, the same subjects received L-NMMA in the dose 6 mg/kg iv over 15 min. The effect of L-NMMA on the maximal mean blood velocity (Vmean) in the middle cerebral artery (MCA) (transcranial Doppler), the luminal diameter of the radial artery (high-frequency ultrasound), mean arterial blood pressure (MAP), heart rate and electrocardiogram were repeatedly followed every 5 min until 60 min after start of the infusion, then every 15 min during the following hour, and at 3 h and 4 h. RESULTS: Inhibition of NOS had no effect on Vmean in MCA or on the diameter of the radial artery, but MAP increased and heart rate decreased dose dependently. With a dose of 6-mg/kg L-NMMA infused over a 15-min period, the maximum MAP increase was 20% 20 min after the start of L-NMMA infusion. The maximum decrease of heart rate was 24% 15 min after start of the L-NMMA infusion. CONCLUSION: L-NMMA in a dose that caused marked changes in systemic blood pressure and heart rate had no effect on cerebral and radial arteries in man.