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Cellular Responses to Experimental Brain Injury
Ramesh Raghupathi,
Tracy K. Mclntosh,
Douglas H. Smith,
Corresponding Author
Ramesh Raghupathi
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Corresponding author: Dr. Ramesh Raghupathi, Division of Neurosurgery, University of Pennsylvania, 7 Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104, USA Tel. +1 (215) 573–3156; Fax +1 (215) 573–3808Search for more papers by this authorTracy K. Mclntosh
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Search for more papers by this authorDouglas H. Smith
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Search for more papers by this authorRamesh Raghupathi,
Tracy K. Mclntosh,
Douglas H. Smith,
Corresponding Author
Ramesh Raghupathi
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Corresponding author: Dr. Ramesh Raghupathi, Division of Neurosurgery, University of Pennsylvania, 7 Hayden Hall, 3320 Smith Walk, Philadelphia, PA 19104, USA Tel. +1 (215) 573–3156; Fax +1 (215) 573–3808Search for more papers by this authorTracy K. Mclntosh
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Search for more papers by this authorDouglas H. Smith
Division of Neurosurgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA
Search for more papers by this authorAbstract
Little is known regarding the molecular (genomic) events associated with the pathophysiology of traumatic brain injury (TBI). This review focusses on the experimental efforts to date elucidating the acute alterations in expression of immediate early genes (IEGs), heat shock proteins (HSPs) and cytokines following experimental brain injury. The immediate early genes, c-fos, c-jun and junB were observed to be bilaterally induced in the cortex and hippocampus as early as 5 min following lateral fluid-percussion (FP) brain injury in the rat. While levels of c-fos and junB mRNA returned to control levels by 2h, c-jun mRNA remained elevated up to 6h post-injury. Increased levels of mRNA for the inducible heat-shock protein (hsp72) were observed up to 12h following injury and were restricted to the cortex ipsilateral to the impact site. Mild induction of the glucose-regulated proteins (grp78 and grp94), which share sequence homology with hsp72, was apparent in the ipsilateral cortex. The cytokines IL-1β and TNFα were induced at 1h following FP brain injury and remained elevated up to 6h post-injury. These data, while indicative of the complex genomic response to TBI, are also suggestive of the trauma-induced activation of multiple signal transduction pathways.
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