Astrocytes Are the Major Source of Nerve Growth Factor Upregulation Following Traumatic Brain Injury in the Rat

• Published in: Experimental neurology Vol. 149; no. 2; pp. 301 - 309
• Main Authors: Goss, James R., O'Malley, Mark E., Zou, Lanling, Styren, Scot D., Kochanek, Patrick M., DeKosky, Steven T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.02.1998; Elsevier
• Subjects: Animals; astrocyte; Astrocytes - metabolism; Astrocytes - pathology; Biological and medical sciences; Brain Injuries - metabolism; Brain Injuries - pathology; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Gene Expression Regulation; Glial Fibrillary Acidic Protein - biosynthesis; hippocampus; Hippocampus - metabolism; Hippocampus - pathology; hypothermia; Hypothermia, Induced; In Situ Hybridization; in situhybridization; Injuries of the nervous system and the skull. Diseases due to physical agents; Male; Medical sciences; nerve growth factor; Nerve Growth Factors - biosynthesis; Rats; Rats, Sprague-Dawley; Time Factors; Transcription, Genetic; Traumas. Diseases due to physical agents; traumatic brain injury; traumatic brain injury; hippocampus; hypothermia; in situhybridization; nerve growth factor; astrocyte; Molecular hybridization; Cerebral cortex; Rat; Immunocytochemistry; Craniocerebral; In situ; Diseases of the osteoarticular system; Nerve growth factor; Induced hypothermia; Genetics; Quantitative analysis; Nervous system diseases; Cytokine; Rodentia; General anesthesia; Astrocyte; Trauma; Cerebral disorder; Pathology; Vertebrata; Experimental disease; Mammalia; Polypeptide; Animal; Central nervous system disease; Skull disease; Molecular biology; Hippocampus; Growth factor
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.1997.6712

Previous studies from our group have demonstrated an upregulation in nerve growth factor (NGF) RNA and protein in the cortex 24 h following traumatic brain injury (TBI) in a rat model. This increase in NGF is suppressed if rats are subjected to 4 h of whole-body hypothermia following TBI. In the present study we usedin situhybridization to extend our initial RNA gel-blot (Northern) hybridization findings by demonstrating that NGF RNA is increased in the cortex following TBI and that hypothermia diminishes this response. Further, by combiningin situhybridization with immunocytochemistry for glial fibrillary acidic protein we demonstrate that astrocytes are the major cellular source for the upregulation in NGF and that this upregulation can be observed in the hippocampus as early as 3 h posttrauma. The predominantly astrocytic origin suggests that the NGF upregulation is not related primarily to cholinotrophic activities. We hypothesize that its function is to stimulate upregulation of antioxidant enzymes, as part of an injury-induced cascade, and that supplementation of NGF or antioxidants may be warranted in hypothermic therapies for head injury.