Cerebral hemidecortication alters expression of transforming growth factor alpha mRNA in the neostriatum of developing rats.
Transforming growth factor alpha (TGF alpha) is a mitogenic polypeptide which acts at the epidermal growth factor receptor to produce its biologic effects. Recent studies have demonstrated that TGF alpha may act as a neurotrophic factor. Cerebral hemispherectomy (hemidecortication) is performed on some children with intractable epilepsy. Prior studies have demonstrated improved functional recovery in both children and animals when the surgery is performed at a very early age. In order to test whether TGF alpha may be involved in the functional recovery of the neostriatum following cerebral hemidecortication, we performed in situ hybridization for TGF alpha mRNA on brains of rats which underwent hemispherectomy at postnatal day (P) 6 or P12 or in adulthood, and sacrificed one, 7, or 30 days following surgery. Normal striatal expression in control animals was very high at P6 and then decreased throughout development. In animals undergoing lesion at earlier ages (P6 and P12), TGF alpha mRNA expression was first depressed in the ipsilateral neostriatum one day after surgery and then elevated to supranormal levels 7 and 30 days after surgery. Maximal decreases (40% below contralateral neostriatum) were seen in animals lesioned at P12 and sacrificed the next day. Maximal elevations (60% greater than opposite neostriatum) were seen in animals operated on at P6 and sacrificed 30 days post surgery. Expression in the adult animal was only mildly affected, with a 20% increase found in the ipsilateral caudate 7 days after the lesion, but no significant changes after one or 30 days survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Kornblum
H I
HI
Department of Pediatrics, UCLA School of Medicine 90024.
Chugani
H T
HT
Tatsukawa
K
K
Gall
C M
CM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002421:Caudate Nucleus / Q000254:growth & development / Q000378:metabolism*; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D008297:Male; D017072:Neostriatum / Q000254:growth & development / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha