Neuroprotective effects of ebselen in traumatic brain injury model: involvement of nitric oxide and p38 mitogen-activated protein kinase signalling pathway

2014 ◽  
Vol 41 (2) ◽  
pp. 134-138 ◽  
Author(s):  
Liang Wei ◽  
Yanfei Zhang ◽  
Cheng Yang ◽  
Qi Wang ◽  
Zhongwei Zhuang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Neuroprotective Effects ◽  
Traumatic Brain Injury Model ◽  
Injury Model ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signalling

scholarly journals Differential Activation of Mitogen-Activated Protein Kinase Pathways after Traumatic Brain Injury in the Rat Hippocampus

2002 ◽  
Vol 22 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Naoki Otani ◽  
Hiroshi Nawashiro ◽  
Shinji Fukui ◽  
Namiko Nomura ◽  
Akiko Yano ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Kinase ◽  
Pyramidal Cell ◽  
Pyramidal Neurons ◽  
Rat Hippocampus ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Cell Layers

Mitogen-activated protein kinases, which play a crucial role in signal transduction, are activated by phosphorylation in response to a variety of mitogenic signals. In the present study, the authors used Western blot analysis and immunohistochemistry to show that phosphorylated extracellular signal-regulated protein kinase (p-ERK) and c-Jun NH(2)-terminal kinase (p-JNK), but not p38 mitogen-activated protein kinase, significantly increased in both the neurons and astrocytes after traumatic brain injury in the rat hippocampus. Different immunoreactivities of p-ERK and p-JNK were observed in the pyramidal cell layers and dentate hilar cells immediately after traumatic brain injury. Immunoreactivity for p-JNK was uniformly induced but was only transiently induced throughout all pyramidal cell layers. However, strong immunoreactivity for p-ERK was observed in the dentate hilar cells and the damaged CA3 neurons, along with the appearance of pyknotic morphologic changes. In addition, immunoreactivity for p-ERK was seen in astrocytes surrounding dentate and CA3 pyramidal neurons 6 hours after traumatic brain injury. These findings suggest that ERK and JNK but not p38 cascades may be closely involved in signal transduction in the rat hippocampus after traumatic brain injury.

scholarly journals Mitogen-Activated Protein Kinase Pathways Following Traumatic Brain Injury

2011 ◽  
Vol 02 (03) ◽  
pp. 208-216 ◽  
Author(s):  
Naoki Otani ◽  
Hiroshi Nawashiro ◽  
Kimihiro Nagatani ◽  
Satoru Takeuchi ◽  
Hiroaki Kobayashi ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

scholarly journals Mitogen-Activated Protein Kinase Inhibition in Traumatic Brain Injury: In Vitro and In Vivo Effects

2002 ◽  
Vol 22 (4) ◽  
pp. 444-452 ◽  
Author(s):  
Tatsuro Mori ◽  
Xiaoying Wang ◽  
Jae-Chang Jung ◽  
Toshihisa Sumii ◽  
Aneesh B. Singhal ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Acute Injury ◽  
Mechanical Trauma ◽  
P38 Kinase ◽  
Mitogen Activated Protein

The authors provide the first in vitro and in vivo evidence that perturbations in mitogen-activated protein kinase (MAPK) signal-transduction pathways are involved in the pathophysiology of traumatic brain injury. In primary rat cortical cultures, mechanical trauma induced a rapid and selective phosphorylation of the extracellular signal-regulated kinase (ERK) and p38 kinase, whereas there was no detectable change in the c-jun N-terminal kinase (JNK) pathway. Treatment with PD98059, which inhibits MAPK/ERK 1/2, the upstream activator of ERK, significantly increased cell survival in vitro. The p38 kinase and JNK inhibitor SB203580 had no protective effect. Similar results were obtained in vivo using a controlled cortical impact model of traumatic injury in mouse brain. Rapid and selective upregulation occurred in ERK and p38 pathways with no detectable changes in JNK. Confocal immunohistochemistry showed that phospho-ERK colocalized with the neuronal nuclei marker but not the astrocytic marker glial fibrillary acidic protein. Inhibition of the ERK pathway with PD98059 resulted in a significant reduction of cortical lesion volumes 7 days after trauma. The p38 kinase and JNK inhibitor SB203580 had no detectable beneficial effect. These data indicate that critical perturbations in MAPK pathways mediate cerebral damage after acute injury, and further suggest that ERK is a novel therapeutic target in traumatic brain injury.

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