Melatonin Promotes Oligodendroglial Maturation of Injured White Matter in Neonatal Rats

OBJECTIVE:To investigate the effects of melatonin treatment in a rat model of white matter damage (WMD) in the developing brain. Additionally, we aim to delineate the cellular mechanisms of melatonin effect on the oligodendroglial cell lineage. METHODS:A unilateral ligation of the uterine artery in pregnant rat at the embryonic day 17 induces fetal hypoxia and subsequent growth restriction (GR) in neonatal pups. GR and control pups received a daily intra-peritoneal injection of melatonin from birth to post-natal day (P) 3. RESULTS:Melatonin administration was associated with a dramatic decrease in microglial activation and astroglial reaction compared to untreated GR pups. At P14, melatonin prevented white matter myelination defects with an increased number of mature oligodendrocytes (APC-immunoreactive) in treated GR pups. Conversely, melatonin was not found to be associated with an increased density of total oligodendrocytes (Olig2-immunoreactive), suggesting that melatonin is able to promote oligodendrocyte maturation but not proliferation. These effects appear to be melatonin-receptor dependent and were reproduced in vitro. INTERPRETATION:These data suggest that melatonin has a strong protective effect on developing damaged white matter through decreased microglial activation and oligodendroglial maturation leading to a normalization of the myelination process. Consequently, melatonin should be a considered as an effective neuroprotective candidate not only in perinatal brain damage but also in inflammatory and demyelinating diseases observed in adults

Esomeprazole-induced hyperchromograninemia in the absence of concomitant hypergastrinemia

Abstract BACKGROUND: A 37-year-old female, who had a neuroendocrine pancreatic neoplasm, underwent duodeno-cephalo-pancreatectomy. In the 2 years following surgery, she had normal levels of serum chromogranin A (CgA), gastrin and other tumor markers. About 3 years after surgery, owing to the onset of reflux-like dyspeptic symptoms, the patient started treatment with the PPI esomeprazole. During PPI treatment, the patient's serum CgA level rose to more than three times the upper limit of normal, although her gastrin levels remained in the normal range. These findings were interpreted as being suggestive of neuroendocrine tumor relapse. INVESTIGATIONS: Thoraco-abdominal CT, In¹¹¹-octreotide total body scan, CT of sella turcica, Tc(99m)-sestamibi neck scan, mutational analysis of chromosome 11q13 (site of multiple endocrine neoplasia type 1 [MEN1] gene). Discontinuation of, and rechallenge with, esomeprazole. DIAGNOSIS: Esomeprazole-induced hyperchromograninemia in the absence of elevated levels of fasting serum gastrin. MANAGEMENT: Discontinuation of acid-suppressive treatment and continuation of oncologic follow-up. PMID: 20938461 [PubMed - indexed for MEDLINE

Melatonin promotes myelination by decreasing white matter inflammation after neonatal stroke.

International audienceMelatonin demonstrates neuroprotective properties in adult models of cerebral ischemia, acting as a potent antioxidant and anti-inflammatory agent. We investigated the effect of melatonin in a 7-d-old rat model of ischemia-reperfusion, leading to both cortical infarct and injury in the underlying white matter observed using MRI and immunohistochemistry. Melatonin was given i.p. as either a single dose before ischemia or a double-dose regimen, combining one before ischemia and one 24 h after reperfusion. At 48 h after injury, neither a significant reduction in cortical infarct volume nor a variation in the number of TUNEL- and nitrotyrosine-positive cells within the ipsilateral lesion was observed in melatonin-treated animals compared with controls. However, a decrease in the density of tomato lectin-positive cells after melatonin treatment was found in the white matter underlying cortical lesion. Furthermore, we showed a marked increase in the myelin basic protein-immunoreactivity in the cingulum and in the density of mature oligodendrocytes (APC-immunoreactive) in both the ipsilateral cingulum and external capsule. These results suggest that melatonin is not able to reduce cortical infarct volume in a neonatal stroke model but strongly reduces inflammation and promotes subsequent myelination in the white matter