title: Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage.
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.
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: Tim
authors.initials: T
authors.lastname: Lekic
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Flores
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: Damon
authors.initials: D
authors.lastname: Klebe
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: Desislava
authors.initials: D
authors.lastname: Doycheva
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Rolland
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.affiliation: Division of Physiology and Pharmacology, School of Medicine, Loma Linda, CA, USA. johnzhang3910@yahoo.com.|Department of Neurosurgery, School of Medicine, Loma Linda, CA, USA. johnzhang3910@yahoo.com.|Department of Physiology and Pharmacology, Loma Linda University School of Medicine, 11041 Campus Street, Risley Hall Rm 219, Loma Linda, CA, 92354, USA. johnzhang3910@yahoo.com.
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D001929:Brain Edema; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006849:Hydrocephalus; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020300:Intracranial Hemorrhages / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006454:Hemoglobins; D007334:Insulin-Like Growth Factor I
keywords: Germinal matrix hemorrhage; Hydrocephalus; Neonatal rats; Neurological dysfunction; Stroke, experimental