Genes preferentially induced by depolarization after concussive brain injury: Effects of age and injury severity

• Published in: Journal of neurotrauma Vol. 19; no. 4; pp. 387 - 402
• Main Authors: GIZA, Christopher C, PRINS, Mayumi L, HOVDA, David A, HERSCHMAN, Harvey R, FELDMAN, Jonathan D
• Format: Journal Article
• Language: English
• Published: Larchmont, NY Liebert 01.04.2002; Mary Ann Liebert, Inc
• Subjects: Adults; Age Factors; Animals; Animals, Newborn; Biological and medical sciences; Brain Injuries - genetics; Brain Injuries - metabolism; Brain Injuries - physiopathology; Calcium-Binding Proteins; Cell culture; Cell death; Chromogranins; Concussion; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene expression; Gene Expression Regulation - physiology; Genes, fos - physiology; Genes, Immediate-Early - physiology; Hippocampus - growth & development; Hippocampus - injuries; Hippocampus - pathology; Hippocampus - physiology; Injuries of the nervous system and the skull. Diseases due to physical agents; Kinases; Male; Medical sciences; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Potentials - genetics; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Nuclear Receptor Subfamily 4, Group A, Member 1; Potassium; Protein-Serine-Threonine Kinases - biosynthesis; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Proteins - genetics; Proteins - metabolism; Rats; Rats, Sprague-Dawley; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Synaptotagmins; Transcription Factors - genetics; Transcription Factors - metabolism; Trauma; Traumas. Diseases due to physical agents; Traumatic brain injury; United States > US; California; Nervous system diseases; Pathophysiology; Rat; Enzyme; Transferases; Craniocerebral; Rodentia; Diseases of the osteoarticular system; Gene expression; Trauma; Young animal; Cerebral disorder; Depolarization; Vertebrata; Mammalia; Chromogranin; Protein kinase; Central nervous system disease; Adult animal; Skull disease; Synaptotagmin; Age; Hippocampus; Immediate early gene
• ISSN: 0897-7151; 1557-9042
• DOI: 10.1089/08977150252932352

Fluid percussion (FP) brain injury leads to immediate indiscriminate depolarization and massive potassium efflux from neurons. Using Northern blotting, we examined the post-FP expression of primary response/immediate early genes previously described as induced by depolarization in brain. RNA from ipsilateral and contralateral hippocampus was harvested from immature and adult rats 1 h following mild, moderate, or severe lateral fluid percussion injury and compared against age-matched sham animals. C-fos gene expression was used as a positive control and showed marked induction in both pups (6-25-fold with increasing severity) and adults (9.7-17.1-fold). Kinase-induced-by-depolarization-1 (KID-1) and salt-inducible kinase (SIK) gene expression was increased in adult (KID-1 1.5-1.6-fold; SIK 1.3-3.9-fold) but not developing rats. NGFI-b RNA was elevated after injury in both ages (pups 1.8-6.1-fold; adults 3.5-5-fold), in a pattern similar to that seen for c-fos. Secretogranin I (sec I) demonstrated no significant changes. Synaptotagmin IV (syt IV) was induced only following severe injury in the immature rats (1.4-fold). Our results reveal specific severity- and age-dependent patterns of hippocampal immediate early gene expression for these depolarization-induced genes following traumatic brain injury. Differential expression of these genes may be an important determinant of the distinct molecular responses of the brain to varying severities of trauma experienced at different ages.