Simultaneous glutamate and GABA(A) receptor agonist administration increases calbindin levels and prevents hippocampal damage induced by either agent alone in a model of perinatal brain injury

Perinatal brain injury is associated with the release of amino acids, principally glutamate and GABA, resulting in massive increases in intracellular calcium and eventual cell death. We have previously demonstrated that independent administration of kainic acid (KA), an AMPA/kainate receptor agonist, or muscimol, a GABA(A) receptor agonist, to newborn rats results in hippocampal damage [Hilton, G.D., Ndubuizu, A., and McCarthy, M.M., 2004. Neuroprotective effects of estradiol in newborn female rat hippocampus. Dev. Brain Res. 150, 191-198; Hilton, G. D., Nunez, J.L. and McCarthy, M.M., 2003. Sex differences in response to kainic acid and estradiol in the hippocampus of newborn rats. Neuroscience. 116, 383-391; Nunez, J.L. and McCarthy, M.M., 2003. Estradiol exacerbates hippocampal damage in a model of preterm infant brain injury. Endocrinology. 144, 2350-2359; Nunez, J.L., Alt, J.J. and McCarthy, M.M., 2003. A new model for prenatal brain damage. I. GABA(A) receptor activation induces cell death in developing rat hippocampus. Exp. Neurol. 181, 258-269]. We now report that KA or muscimol alone administered to immature hippocampal neurons in culture induces significant cell death as evidenced by TUNEL assay. Surprisingly, simultaneous administration of equimolar quantities of these two agonists blocks the effect of either one alone. Moreover, treatment of newborn pups results in less damage compared to either muscimol or KA alone. We further observed that immunoreactivity for the calcium-binding protein, calbindin D(28K), is increased in the brains of pups simultaneously administered KA and muscimol as compared to either alone.     

Brain tissue oxygen concentration measurements

Brain function depends exquisitely on oxygen for energy metabolism. Measurements of brain tissue oxygen tension, by a variety of quantitative and qualitative techniques, going back for >50 years, have led to a number of significant conclusions. These conclusions have important consequences for understanding brain physiology as it is now being explored by techniques such as blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) and near-infrared spectroscopy (NIRS). It has been known for some time that most of the measured oxygen tensions are less than venous pO2 and are distributed in a spatially and temporally heterogeneous manner on a microregional scale. Although certain large-scale methods can provide reproducible average brain pO2 measurements, no useful concept of a characteristic oxygen tension or meaningful average value for brain tissue oxygen can be known on a microregional level. Only an oxygen field exists with large local gradients due to local tissue respiration, and the most useful way to express this is with a pO2 distribution curve or histogram. The neurons of the brain cortex normally exist in a low-oxygen environment and on activation are oxygenated by increases in local capillary blood flow that lead to increases in hemoglobin saturation and tissue oxygen.     

Omentin plasma levels and gene expression are decreased in obesity

Central obesity and the accumulation of visceral fat are risk factors for the development of type 2 diabetes and cardiovascular disease. Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue that increases insulin sensitivity in human adipocytes. To determine the impact of obesity-dependent insulin resistance on the regulation of two omentin isoforms, gene expression and plasma levels were measured in lean, overweight, and obese subjects. Omentin 1 was shown to be the major circulating isoform in human plasma. Lean subjects had significantly higher plasma omentin 1 levels than obese and overweight subjects. In addition, higher plasma omentin 1 levels were detected in women compared with men. Plasma omentin 1 levels were inversely correlated with BMI, waist circumference, leptin levels, and insulin resistance as measured by homeostasis model assessment and positively correlated with adiponectin and HDL levels. Both omentin 1 and omentin 2 gene expression were decreased with obesity and were highly correlated with each other in visceral adipose tissue. In summary, decreased omentin levels are associated with increasing obesity and insulin resistance. Therefore, omentin levels may be predictive of the metabolic consequences or co-morbidities associated with obesity.     

Neuroprotective effects of estradiol in newborn female rat hippocampus

Perinatal brain injury, consequent to hypoxic/ischemic events, is associated with the release of excess excitatory neurotransmitters, including glutamate. We have previously shown that administration of a glutamate receptor agonist, kainic acid (KA), to postnatal day 0 (PN0) and PN1 rats results in damage selective to the dentate gyrus of females. Pretreatment with the gonadal steroid estradiol prevents KA-induced damage to the female dentate gyrus. To begin to elucidate the cellular mechanism of the neuroprotective effects of estradiol in neonatal females, we have employed the estrogen receptor antagonists Tamoxifen and ICI 182,780 in vivo and in vitro, respectively. Peripheral administration of Tamoxifen, which crosses the blood-brain barrier, prevented estradiol-mediated neuroprotection against KA-induced damage in the dentate gyrus. The highly selective estrogen receptor antagonist ICI 182,780, which does not penetrate into the brain from the periphery, also prevented estradiol's protective effects on KA-induced cell death in cultured hippocampal neurons but only late in the time course of injury. The data suggest that the neuroprotection afforded by estradiol against KA-induced injury in the female is estrogen receptor mediated but may include an additional mechanism that is not antagonized at the receptor.     

Osteolipoma of the palate: report of a case and review of the literature

Oral lipomas, though rare, predominantly affect the buccal mucosa, tongue, and lips. The occurrence of lipomas in the palate is extremely rare. Osteolipoma is a very rare histological variant of lipoma accounting for less than 1% of all cases. Although a few cases involving the soft palate have been reported, there is only one reported case of osteolipoma of the hard palate in the English-language literature and it was a congenital osteolipoma associated with a cleft palate in a 6-year-old male child. This paper aims to describe an additional case uniquely located in the hard palate of an adult female.