No effect of ablation of surfactant protein-D on acute cerebral infarction in mice

BACKGROUND: Crosstalk between the immune system in the brain and the periphery may contribute to the long-term outcome both in experimental and clinical stroke. Although, the immune defense collectin surfactant protein-D (SP-D) is best known for its role in pulmonary innate immunity, SP-D is also known to be involved in extrapulmonary modulation of inflammation in mice. We investigated whether SP-D affected cerebral ischemic infarction and ischemia-induced inflammatory responses in mice. METHODS: The effect of SP-D was studied by comparing the size of ischemic infarction and the inflammatory and astroglial responses in SP-D knock out (KO) and wild type (WT) mice subjected to permanent middle cerebral artery occlusion. SP-D mRNA production was assessed in isolated cerebral arteries and in the whole brain by PCR, and SP-D protein in normal appearing and ischemic human brain by immunohistochemistry. Changes in plasma SP-D and TNF were assessed by ELISA and proximity ligation assay, respectively. RESULTS: Infarct volumetric analysis showed that ablation of SP-D had no effect on ischemic infarction one and five days after induction of ischemia. Further, ablation of SP-D had no effect on the ischemia-induced increase in TNF mRNA production one day after induction of ischemia; however the TNF response to the ischemic insult was affected at five days. SP-D mRNA was not detected in parenchymal brain cells in either naïve mice or in mice subjected to focal cerebral ischemia. However, SP-D mRNA was detected in middle cerebral artery cells in WT mice and SP-D protein in vascular cells both in normal appearing and ischemic human brain tissue. Measurements of the levels of SP-D and TNF in plasma in mice suggested that levels were unaffected by the ischemic insult. Microglial-leukocyte and astroglial responses were comparable in SP-D KO and WT mice. CONCLUSIONS: SP-D synthesis in middle cerebral artery cells is consistent with SP-D conceivably leaking into the infarcted area and affecting local cytokine production. However, there was no SP-D synthesis in parenchymal brain cells and ablation of SP-D had no effect on ischemic cerebral infarction

Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A(2A) receptors

Aims: Adenosine plays an important role in the regulation of heart rate (HR) and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, this study investigated the effect of the nucleoside on mean arterial blood pressure (MAP) and HR in conscious mice. Methods: Chronic indwelling catheters were placed in C57Bl/6J (WT) and endothelial nitric oxide synthase knockout (eNOS -/-) mice for continuous measurements of MAP and HR. Using PCR and myograph analysis, involvement of adenosine receptors was investigated in human and mouse renal blood vessels. Results: Bolus infusion of 0.5mgkg -1 adenosine elicited significant transient decreases in MAP (99.3±2.3 to 70.4±4.5mmHg) and HR (603.2±18.3 to 364.3±49.2min -1), which were inhibited by the A 2A receptor antagonist ZM 241385. Activation of adenosine A 2A receptors with CGS 21680 (0.02mgkg -1) caused a significant reduction in MAP from 99.6±1.2 to 73.1±3.6mmHg accompanied by tachycardia (610.5±9.3 to 677.5±9.5min -1). The reduction in MAP observed after adenosine or CGS 21680 administrations was not significantly different in WT and eNOS -/- mice. In isolated human and mouse intrarenal arteries, adenosine caused a relaxation dependent on A 2A adenosine receptor activation. A 2A receptors were present in both human and mouse arteries whereas A 1 and A 2B receptors were only present in mouse arteries. Conclusion: In conclusion, acute adenosine administration and selective stimulation of adenosine A 2A receptors results in an immediate, transient eNOS-independent reduction in MAP. A 2A receptor activation causes relaxation of human and mouse arteries. © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.link_to_subscribed_fulltex