Fast and widespread increase of basic fibroblast growth factor messenger RNA and protein in the forebrain after kainate-induced seizures.
Basic fibroblast growth factor promotes the survival and outgrowth of neurons and protects neurons from glutamate mediated excitotoxicity. The present study investigates the effects of kainate-induced epileptic seizures on the cellular expression of basic fibroblast growth factor messenger RNA and protein. Seizures were induced by injection of 12 mg/kg kainic acid. Rats were killed 3 h, 6 h, and 24 h after injection of the drug and analysed by radioactive and non-radioactive in situ hybridization as well as immunohistochemistry for glial fibrillary acidic protein and basic fibroblast growth factor. Radioactive in situ hybridization revealed a fast (6 h), strong (300-400% of control) and widespread increase of basic fibroblast growth factor messenger RNA after kainate-induced seizures. Non-radioactive in situ hybridization using digoxigenin-labeled riboprobes combined with glial fibrillary acidic protein immunohistochemistry showed that basic fibroblast growth factor messenger RNA was markedly increased in astroglial cells throughout the brain. Immunohistochemistry for basic fibroblast growth factor revealed labeling of nuclei in astrocytes in many forebrain areas and in neurons in area CA2 and fasciola cinereum. Kainate markedly increased basic fibroblast growth factor-like immunoreactivity in nuclei of astrocytes in several forebrain areas. This effect peaked 24 h after injection. It is concluded that basic fibroblast growth factor may play a neuroprotective role in kainate mediated excitotoxicity as seen from a massive and widespread astroglial increase in basic fibroblast growth factor messenger RNA and -like immunoreactivity. These effects may, to a large degree, be mediated through the excessive release of endogenous glutamate, induced by the epileptic seizures, leading to activation of glutamate receptors on astroglial cells through volume transmission, i.e. via diffusion of electrochemical signals in the extracellular fluid pathways.
Humpel
C
C
Department Histology & Neurobiology, Karolinska Institute, Stockholm, Sweden.
Lippoldt
A
A
Chadi
G
G
Ganten
D
D
Olson
L
L
Fuxe
K
K
D000818:Animals; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007608:Kainic Acid; D016548:Prosencephalon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*
D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D007608:Kainic Acid