Abstract
Periventricular leukomalacia (PVL) is a major form of brain damage in premature infants. This study was to test whether IGF-1 can prevent PVL-like brain damage induced by lipopolysaccharide (LPS) in the neonatal rat. Intraventricular delivery of LPS resulted in an acute brain inflammatory response, i.e., rapid recruitment of polymorphonuclear leukocytes (PMNs), activation of microglia and astrocytes, and induction of IL-1β (IL1β) expression. Brain inflammation was associated with the loss of O4+ preoligodendrocytes (preOLs), a decrease of myelin basic protein (MBP) in the white matter and an increase of pyknotic cells in the cortex. IGF-1 at a low dose significantly prevented LPS-induced deleterious effects without alteration of IL-1β expression and microglia/astrocytes activation. On the other hand, the low dose of IGF-1 enhanced LPS-induced PMNs recruitment and blood-brain barrier (BBB) permeability, and caused intracerebral hemorrhage. At higher doses, co-application of IGF-1 with LPS resulted in a high mortality rate. Brains from the surviving rats showed massive PMN infiltration and intracerebral hemorrhage. However, these adverse effects were not found in rats treated with IGF-1 alone. This study provides the alarming evidence that in an acute inflammatory condition, IGF-1 may have severe, harmful effects on the developing brain.
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Abbreviations
- BBB:
-
blood-brain barrier
- GFAP:
-
glial fibrillary acidic protein
- H&E:
-
hematoxylin and eosin
- IGF-1:
-
insulin-like growth factor-1
- LPS:
-
lipopolysaccharide
- MBP:
-
myelin basic protein
- PMN:
-
polymorphonuclear leukocyte
- Pre-OLs:
-
pre-oligodendrocyte
- PVL:
-
periventricular leukomalacia
- TUNEL:
-
terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
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Supported in part by HD 35496 from the National Institute of Child Health and Human Development; by NS 54278 from the National Institute of Neurological Disorders and Stroke; and by funds from the Newborn Medicine Division and the Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
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Pang, Y., Zheng, B., Campbell, L. et al. IGF-1 Can Either Protect Against or Increase LPS-Induced Damage in the Developing Rat Brain. Pediatr Res 67, 579–584 (2010). https://doi.org/10.1203/PDR.0b013e3181dc240f
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DOI: https://doi.org/10.1203/PDR.0b013e3181dc240f
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