Prenatal exposure to ethanol alters the neuroimmune response to a central nervous system wound in the adult rat.
We examined the long-term effects of in utero ethanol exposure on the expression of tumor necrosis factor-alpha (TNF-alpha), glial fibrillary acidic protein (GFAP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and ED1 in the tissue at the site of a central nervous system (CNS) wound. Adult rats obtained from dams fed control diets or an ethanol diet were fed either control diets or an ethanol diet 5 days before and after infliction of a CNS wound. In pair-fed controls, the expression of TNF-alpha, GFAP, ICAM-1, VCAM-1, and ED1 immunoreactive proteins was increased in the tissue at the wound site when compared with that in nonlesioned tissues. In adult rats previously exposed to ethanol in utero and then fed a liquid diet before and after infliction of a CNS wound, however, expression of TNF-alpha, GFAP, and ICAM-1 was markedly decreased when compared with findings in pair-fed controls. In contrast, VCAM-1 levels and ED1 immunoreactive proteins were markedly increased when compared with findings for pair-fed controls. Furthermore, in adult rats exposed to ethanol in utero, re-exposure to ethanol before and after sustaining a CNS wound resulted in further decreases in TNF-alpha, GFAP, and ICAM-1 levels and marked increases in VCAM-1 levels and ED1 immunoreactive proteins. Results of these studies suggest to us that prenatal exposure to ethanol has a long-term immunoteratogenic effect in the CNS, resulting in altered responses of key components of the neuroimmune response, which could leave the animal immunocompromised as an adult.
DeVito
W J
WJ
Division of Endocrinology, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA 01655, USA. william.devito@umassmed.edu
Stone
S
S
D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D053331:Ectodysplasins; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000037:antagonists & inhibitors; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D053331:Ectodysplasins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000431:Ethanol