Hyperbilirubinemia protects against focal ischemia in rats

Abstract

Heme oxygenase-1 (HO1) catalyzes oxidation of the heme molecule in concert with NADPH-cytochrome P450 reductase following the specific cleavage of heme into carbon monoxide, iron, and biliverdin, which is rapidly metabolized to bilirubin. HO1 is a stress-inducible protein that protects cells against oxidative injury, but its protective mechanism is not fully understood. The Eizai hyperbilirubinemic rat (EHBR), a mutant strain derived from the Sprague-Dawley rat (SDR), has a mutation in the gene for the canalicular multispecific organic anion transporter, which results in a phenotype of hyperbilirubinemia, and thus is a model of Dubin-Johnson syndrome in humans. In this study, we compared EHBR and SDR with regard to neuronal death induced by 2 hr of occlusion of the middle cerebral artery and reperfusion. In EHBR, the area that was immunoreactive for microtubule-associated protein-2 was significantly reduced, and the HO1-immunoreactive area was smaller than that in SDR. These results suggest that bilirubin has essentially a neuroprotective effect against focal ischemia and may participate in HO1-induced neuroprotection.

Aggressive dogs are characterized by low omega-3 polyunsaturated fatty acid status

“…However, it would be tempting to speculate that this phenomenon may occur via a central neuroprotective effect of bilirubin. This would be in line with previous data showing that bilirubin may exert significant neuroprotective actions (Kitamura et al 2003).…”

Involvement of Wiskott-Aldrich Syndrome Protein Family Verprolin-Homologous Protein (WAVE) and Rac1 in the Phagocytosis of Amyloid-β(1 – 42) in Rat Microglia

“…For the semi-quantitative analysis, images of Ab immunoreactivity in microglia were scanned using a laser scanning confocal microscope LSM410 and then analyzed (WinRoof; Mitani, Fukui) (31). The Abimmunoreactive areas in the cytosolic (inner space of phalloidin-staining) region and the cell surface (double staining of phalloidin and anti-Ab antibody) region and total Ab-immunoreactive area were measured (mm 2 ).…”

Intracerebroventricular Injection of Microglia Protects Against Focal Brain Ischemia

“…Cultured microglia were labeled by the fluorescent dye PKH26 (Sigma, St. Louis, MO, USA) (6) and then injected i.c.v. MCA occlusion was also performed in male Wistar rats (weighing approximately 300 g) as described previously (7). Selected rats were anesthetized (sodium pentobarbital, 50 mg / kg, i.p.)…”