Acute activation of mitogen-activated protein kinases following traumatic brain injury in the rat: implications for posttraumatic cell death

• Published in: Experimental neurology Vol. 183; no. 2; pp. 438 - 448
• Main Authors: Raghupathi, Ramesh, Muir, Judith K, Fulp, Carl T, Pittman, Randall N, McIntosh, Tracy K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-10-2003; Elsevier
• Subjects: Animals; Apoptosis; Biological and medical sciences; Brain Injuries - enzymology; Brain Injuries - pathology; c-Jun N-terminal kinase; Cell Death; Cerebral Cortex - enzymology; Cerebral Cortex - pathology; Disease Models, Animal; Disease Progression; Enzyme Activation; Extracellular signal-regulated kinase; Head injury; Hippocampus - enzymology; Hippocampus - pathology; Injuries of the nervous system and the skull. Diseases due to physical agents; JNK Mitogen-Activated Protein Kinases; Male; Medical sciences; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Neurodegeneration; Neurons - enzymology; Neurons - pathology; Rats; Rats, Sprague-Dawley; Signal Transduction; Thalamus - enzymology; Thalamus - pathology; Traumas. Diseases due to physical agents; Traumatic axonal injury; Extracellular signal-regulated kinase; c-Jun N-terminal kinase; Traumatic axonal injury; Head injury; Neurodegeneration; Apoptosis; Immunohistochemistry; Phosphorylation; Rat; Craniocerebral; Encephalon; Thalamus; Human; Cartography; Nervous system diseases; Enzyme; Transferases; Rodentia; White matter; Trauma; Cerebral disorder; Neurodegeneraition; Vertebrata; Mammalia; Cell death; Protein kinase; Animal; C-Onc gene; Central nervous system disease; Hippocampus
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/S0014-4886(03)00166-3

The regional activation (via phosphorylation) of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signaling pathways was examined using immunoblotting and immunohistochemistry following experimental brain injury. Anesthetized rats were subjected to lateral fluid-percussion brain injury of moderate severity (2.4–2.6 atm) and euthanized at 2, 6, 24, and 72 h after injury; sham-injured animals were surgically prepared but were not injured. Immunohistochemical evidence of activation of JNK and ERK1/2 pathways was observed predominantly in regions that exhibit neural cell apoptosis and axonal damage following brain trauma. Activation of the ERK1/2 pathway was observed as early as 2 h and up to 72 h postinjury in nonneuronal cells in all layers of the cortex at the site of maximal injury, in the white matter below the site of maximal cortical damage and in the thalamus. In contrast, activation of JNK signaling was observed only at 24 and 72 h postinjury in a few neurons at the core of the cortical injury site. However, robust JNK activation was observed between 2 and 72 h postinjury in both axons and nonneuronal cells in the white matter below the site of maximal cortical damage and in the thalamus. Activation of ERK1/2, but not JNK, was observed in cells in the dentate hilus in the hippocampus in both hemispheres between 2 and 24 h postinjury. Immunoblotting analyses of extracts from various brain regions did not reveal significant alterations in intensities of either total or phosphorylated proteins underscoring the focal nature of the immunohistochemical observations. However, these results suggest that activation of MAP kinase signaling pathways may be associated with posttraumatic cell damage and are indicative of the heterogeneous nature of the mechanisms underlying regional cell death following TBI.