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Activation of mitogen-activated protein kinases in experimental cerebral ischemia
F Lennmyr1, S Karlsson, P Gerwins
1Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden. fredrik.lennmyr@medsci.uu.se
Objectives:
Mitogen-activated protein kinases (MAPK) regulate cell survival and differentiation. The aim of the present study is to investigate the activation pattern of different MAPKs [extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase (JNK) and p38] after cerebral ischemia.
Material And Methods:
Rats were subjected to cerebral ischemia using a model for transient (2 h) and permanent middle cerebral artery occlusion (MCAO). The rats were allowed 6 h to 1 week of survival before immunohistochemical evaluation with phospho-specific antibodies, recognizing activated MAPKs.
Results:
ERK was activated in ipsilateral blood vessels, neurons and glia, but also in contralateral vessels. JNK activation was absent in neurons but appeared in arterial blood vessels and glia at the lesion side. Active p38 was observed in macrophages in maturing infarcts.
Conclusions:
ERK and JNK may participate in the angiogenic response to cerebral ischemia. ERK, but not JNK, was activated in neurons, possibly indicating a pathophysiologic role. Active p38 might be involved in the inflammatory reaction.
Insights
Mitogen-activated protein kinases (MAPKs) like ERK and JNK may aid blood vessel regrowth after stroke. ERK activation in neurons suggests a role in stroke pathology, while p38 activation indicates involvement in inflammation.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Signaling
Background:
- Mitogen-activated protein kinases (MAPKs) are crucial regulators of cell survival and differentiation.
- Understanding MAPK activation patterns following cerebral ischemia is essential for elucidating stroke pathophysiology.
Purpose of the Study:
- To investigate the activation patterns of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase (JNK), and p38 after cerebral ischemia.
- To explore the potential roles of these MAPKs in the cellular and vascular responses to ischemic stroke.
Main Methods:
- Rats underwent transient (2h) and permanent middle cerebral artery occlusion (MCAO) to model cerebral ischemia.
- Immunohistochemical analysis using phospho-specific antibodies was performed on brain tissue from rats surviving 6 hours to 1 week post-MCAO.
- Detection of activated forms of ERK, JNK, and p38.
Main Results:
- Extracellular signal-regulated kinase (ERK) activation was observed in ipsilateral blood vessels, neurons, and glia, as well as contralateral vessels.
- C-jun-N-terminal kinase (JNK) activation was detected in arterial blood vessels and glia at the lesion site but not in neurons.
- Active p38 was localized to macrophages within developing infarcts.
Conclusions:
- ERK and JNK activation may contribute to the angiogenic response following cerebral ischemia.
- Neuronal activation of ERK, but not JNK, suggests a potential pathophysiological role in stroke.
- p38 activation in macrophages indicates its involvement in the inflammatory response to cerebral ischemia.