TY - JOUR
T1 - Extracellular signal-regulated kinase-mediated IL-1-induced cortical neuron damage during traumatic brain injury
AU - Lu, Kwok Tung
AU - Wang, Yi Wen
AU - Wo, Yu Yuan P.
AU - Yang, Yi Ling
N1 - Funding Information:
This work was supported by grants from the National Science Council (NSC 92-2320-B-415-001; NSC 92-2614-B-003-001; NSC 93-2320-B-415-001) of the Republic of China. Our gratitude also goes to the Academic Paper Editing Clinic, National Taiwan Normal University.
PY - 2005/9/23
Y1 - 2005/9/23
N2 - 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 2 m 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-1α (IL-1α), interleukin-1β (IL-1β), 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-1α and IL-1β 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-1α antibody and IL-1β 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.
AB - 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 2 m 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-1α (IL-1α), interleukin-1β (IL-1β), 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-1α and IL-1β 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-1α antibody and IL-1β 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.
KW - IL-1
KW - Mitogen-activated protein kinase
KW - Traumatic brain injuries
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U2 - 10.1016/j.neulet.2005.05.057
DO - 10.1016/j.neulet.2005.05.057
M3 - Article
C2 - 16024175
AN - SCOPUS:22544446790
SN - 0304-3940
VL - 386
SP - 40
EP - 45
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 1
ER -