Expression of brain-derived neurotrophic factor, nerve growth factor, and heat shock protein HSP70 following fluid percussion brain injury in rats.
Traumatic brain injury can induce the expression of stress-related and neurotrophic genes both within the injury site and in distant regions. These genes may affect severity of damage and/or be neuroprotective. We used in situ hybridization to assess the alterations in expression of the heat shock protein HSP70, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) genes in rat brain following moderate fluid-percussion (F-P) injury at various survival times. HSP70 gene expression was induced at and surrounding the injury site as early as 30 min after trauma. This elevated signal spread ventrally and laterally through the ipsilateral cortex and into the underlying white matter over the next few hours. In addition, there was elevated expression in the temporal hippocampus. BDNF was strongly upregulated in the granular cells of the dentate gyrus and in the CA3 hippocampus 2-6 h after injury. Cortical regions at and near the injury site showed no response at the mRNA level. NGF mRNA increased over the granular cells of the dentate gyrus at early time points. There was also a weaker secondary induction of the NGF gene in the contralateral dentate gyrus of some animals. Cortical response was observed in the entorhinal cortex, bilaterally, but not at the injury site. All three of the studied genes responded quickly to injury, as early as 30 min. The induction of gene expression for neurotrophins in regions remote from areas with histopathology may reflect coupling of gene expression to neuronal excitation, which may be associated with neuroprotection and plasticity.
Truettner
J
J
Neurotrauma Research Center, Department of Neurology, University of Miami School of Medicine, Florida 33101, USA. Jessie@stroke.med.miami.edu
Schmidt-Kastner
R
R
Busto
R
R
Alonso
O F
OF
Loor
J Y
JY
Dietrich
W D
WD
Ginsberg
M D
MD
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D013181:Cortical Spreading Depression / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D009414:Nerve Growth Factors / Q000378:metabolism*; D009434:Neural Pathways / Q000293:injuries / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D018840:HSP70 Heat-Shock Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger