title: Cerebral cortical tissue damage after hemorrhagic hypotension in near-term born lambs.
abstract: Hypotension reduces cerebral O(2) supply, which may result in brain cell damage and loss of brain cell function in the near-term neonate. The aim is to elucidate 1) to what extent the functional disturbance of the cerebral cortex, as measured with electrocortical brain activity (ECBA), is related to cerebral cortical tissue damage, as estimated by MAP2; and 2) whether there is a relationship between the glutamate, nitric oxide (NO), cGMP pathway and the development of cerebral cortical tissue damage after hemorrhagic hypotension. Seven lambs were delivered at 131 d of gestation. Hypotension was induced by withdrawal of blood until mean arterial blood pressure was reduced to 30% of normotension. Cerebral O(2) supply, consumption, and ECBA were calculated in normotensive conditions and after 2.5 h of hypotension. Concentrations of glutamate and aspartate in cerebrospinal fluid (CSF), NO(2) and NO(3) (NOx) in plasma, and cGMP in cortical brain tissue were determined in both conditions. CSF and brain tissue from siblings were used to determine normotensive values. Cortical neuronal damage was detected after 2.5 h of hypotension. ECBA was negatively related to the severity of the cortical damage. ECBA was related to respectively glutamate, NOx, and cGMP concentrations. In conclusion, cortical neuronal damage is detected after 2.5 h of hemorrhagic hypotension in the near-term born lamb. The damage is reflected by a reduction of ECBA. The glutamate, NOx, cGMP pathway is likely to be involved in the pathogenesis of cerebral cortical damage.
authors.affiliation: Department of Pediatrics, Radbound University Nijmegen Medical Center, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: van Os
authors.forename: Evelyn
authors.initials: E
authors.lastname: van den Tweel
authors.forename: Hans
authors.initials: H
authors.lastname: Egberts
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hopman
authors.forename: Wim
authors.initials: W
authors.lastname: Ruitenbeek
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
authors.forename: Margot
authors.initials: M
authors.lastname: van de Bor
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000209:etiology*; D005260:Female; D018698:Glutamic Acid / Q000134:cerebrospinal fluid; D006470:Hemorrhage / Q000150:complications*; D007022:Hypotension / Q000150:complications*; D009569:Nitric Oxide / Q000134:cerebrospinal fluid; D011247:Pregnancy; D012756:Sheep
chemical_list: D009569:Nitric Oxide; D018698:Glutamic Acid