title: Disruption of the blood-brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes.
abstract: Exposure of the adult rat brain parenchyma to zinc induces an increase in the intracerebral expression of the metal-binding protein, metallothionein, which is normally confined to astrocytes, ependymal cells, choroid plexus epithelial cells, and brain endothelial cells. Metallothionein is expressed only in diminutive amounts in astrocytes of the neonatal rat brain, which could imply that neonatal rats are devoid of the capacity to detoxify free metals released from a brain wound. In order to examine the influence of a brain injury on the expression of metallothionein in the neonatal brain, PO rats were subjected to a localized freeze lesion of the neocortex of the right temporal cortex. This lesion results in a disrupted blood-brain interface, leading to extravasation of plasma proteins. From 16 h, reactive astrocytosis, defined as an increase in the number and size of cells expressing GFAP and vimentin, was observed surrounding the neocortical lesion site. Astrocytes and pial cells situated adjacent to the area of injury also became positively stained for metallothionein. At 3-6 days post-lesion, the highest level of reactive astrocytes expressing metallothionein was observed. Neo-Timm staining revealed that histochemically reactive zinc had disappeared from the lesion site. Extracellular albumin and metallothionein-positive astrocytes were absent approximately 2 weeks after the lesion, whereas reactive astrocytosis was still observed. These results show that a lesion of the neonatal rat brain induces a transient expression of metallothionein in reactive astrocytes, probably as a response to metals released from the site of the brain injury.
authors.affiliation: Institute of Medical Anatomy, Panum Institute, University of Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Penkowa
authors.forename: T
authors.initials: T
authors.lastname: Moos
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D001798:Blood Proteins / Q000032:analysis; D001812:Blood-Brain Barrier / Q000502:physiology*; D001930:Brain Injuries / Q000503:physiopathology; D002452:Cell Count; D002540:Cerebral Cortex / Q000737:chemistry / Q000166:cytology; D007150:Immunohistochemistry; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015032:Zinc / Q000032:analysis
chemical_list: D001798:Blood Proteins; D008668:Metallothionein; D015032:Zinc