title: Hippocampal immediate early gene transcription in the rat fluid percussion traumatic brain injury model.
abstract: Traumatic brain injury (TBI) is one of the leading causes of neurological disability and death in the USA across all age groups, ethnicities, and incomes. In addition to the short-term morbidity and mortality, TBI leads to epilepsy and severe neurocognitive symptoms, both of which are referenced to post-traumatic hippocampal dysfunction, although the mechanisms of such hippocampal dysfunction are incompletely understood. Here, we study the temporal profile of the transcription of three select immediate early gene (IEG) markers of neuronal hyperactivation, plasticity, and injury, c-fos, brain-derived neurotrophic factor (BDNF), and Bax, in the acute period following the epileptogenic lateral fluid percussion injury in a rodent TBI model. We found that lateral fluid percussion injury leads to enhanced expression of the selected IEGs within 24 h of TBI. Specifically, BDNF and c-fos increase maximally 1-6 h after TBI in the ipsilesional hippocampus, whereas Bax increases in the hippocampus bilaterally in this time window. Antagonism of the N-methyl-D-aspartate-type glutamate receptor by MK801 attenuates the increase in BDNF and Bax, which underscores a therapeutic role for N-methyl-D-aspartate-type glutamate receptor antagonism in the acute post-traumatic time period and suggests a value to a hippocampal IEG readout as an outcome after injury or acute therapeutic intervention.
authors: Departments of aNeurology bNeurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts cDepartment of Neurology, University of Chicago, Chicago, Illinois, USA dDepartment of Neurology, Beijing Aerospace General Hospital eCenter for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing, China.
authors: Yingpeng
authors: Y
authors: Wang
authors: Mustafa Q
authors: MQ
authors: Hameed
authors: Sanjay N
authors: SN
authors: Rakhade
authors: Antonio H
authors: AH
authors: Iglesias
authors: Paul A
authors: PA
authors: Muller
authors: Dan-Lei
authors: DL
authors: Mou
authors: Alexander
authors: A
authors: Rotenberg
mesh_terms: D000208:Acute Disease; D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020318:Rats, Long-Evans; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494828:Bax protein, rat; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; D016291:Dizocilpine Maleate