Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage

Acta Neurochir Suppl. 2016:121:209-12. doi: 10.1007/978-3-319-18497-5_37.

Abstract

Germinal matrix hemorrhage (GMH) is the most devastating neurological problem of premature infants. Current treatment strategies are ineffective and brain injury is unpreventable. Insulin-like growth factor 1 (IGF-1) is an endogenous protein shown to have multiple neuroprotective properties. We therefore hypothesized that IGF-1 would reduce brain injury after GMH. Neonatal rats (P7 age) received stereotactic collagenase into the right ganglionic eminence. The following groups were studied: (1) sham, (2) GMH + vehicle, (3) GMH + intranasal IGF-1. Three days later, the animals were evaluated using the righting-reflex (early neurobehavior), Evans blue dye leakage (blood-brain barrier (BBB) permeability), brain water content (edema), and hemoglobin assay (extent of bleeding). Three weeks later, juvenile rats were tested using a water maze (delayed neurobehavior), and then were sacrificed on day 28 for assessment of hydrocephalus (ventricular size). Intranasal IGF-1 treated animals had improved neurological function, and amelioration of BBB permeability, edema, and re-bleeding. IGF-1 may play a part in protective brain signaling following GMH, and our observed protective effect may offer new promise for treatment targeting this vulnerable patient population.

Keywords: Germinal matrix hemorrhage; Hydrocephalus; Neonatal rats; Neurological dysfunction; Stroke, experimental.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects*
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain / drug effects*
  • Brain Edema
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Disease Models, Animal
  • Hemoglobins / drug effects
  • Hemoglobins / metabolism
  • Hydrocephalus
  • Insulin-Like Growth Factor I / pharmacology*
  • Intracranial Hemorrhages / metabolism*
  • Intracranial Hemorrhages / pathology
  • Intracranial Hemorrhages / physiopathology
  • Permeability
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Hemoglobins
  • Insulin-Like Growth Factor I