Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury.

Traumatic brain injury (TBI) is one of the most prevalent causes of morbidity and mortality in youth. Interleukin-1 (IL-1) has many roles in the brain in addition to mediating glial inflammatory response; it has also been implicated in neurodegenerative diseases. We demonstrated the signal transduction pathway of IL-1 overproduction-induced cortical neuron loss during TBI. A calibrated weight-drop device (450 g weight and 2m height) was used to induce TBI in adult male Sprague-Dawley rats under general anesthesia (sodium pentobarbital: 40 mg/kg, i.p.). Expression of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), extracellular signal-regulated kinase (ERK), Jun, and p-38 were determined by Western blotting and RT-PCR. Neuronal damage was evaluated by microscopic examination. We found both mRNA and proteins of cortical IL-1alpha and IL-1beta increased three hours after TBI. Phosphorylation of ERK significantly increased but there were no significant effects on cortical expression of ERK, Jun and p-38. Administration of ERK inhibitor, PD98059, IL-1alpha antibody and IL-1beta antibody protected animals from TBI-induced neuronal damage. Our results suggest that TBI-induced cortical neuron death was mediated by the IL-1 receptor through ERK phosphorylation.

Pubmed ID: 16024175