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The Application Of Permanent Middle Cerebral Artery Ligation in the Mouse
Published on: July 25, 2011
CART protects brain from damage through ERK activation in ischemic stroke
Jia Jia1, Xuemei Chen, Wenjing Zhu
1Department of Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, PR China.
Cocaine and amphetamine-regulated transcript (CART) protects the brain from stroke. CART knockdown worsened brain damage and cell death, indicating CART’s neuroprotective role via the ERK pathway.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Cocaine and amphetamine-regulated transcript (CART) is a neuropeptide with known neuroprotective functions.
- Cerebral ischemia, a major cause of stroke, leads to significant neuronal damage and brain injury.
Purpose of the Study:
- To investigate the role of CART in protecting brain tissue against ischemic injury.
- To elucidate the signaling pathway through which CART exerts its neuroprotective effects.
Main Methods:
- Small interference RNA (siRNA) was used to knock down CART expression in vitro and in vivo.
- Neuronal cell death was induced by oxygen and glucose deprivation (OGD) in vitro.
- Infarct size was measured in a mouse middle cerebral artery occlusion (MCAO) model.
- MAPK pathway activation (ERK 1/2, p38, JNK) was assessed using Western blotting and specific pathway antagonists.
Main Results:
- CART knockdown significantly reduced CART mRNA and protein levels, exacerbating neuronal cell death after OGD.
- CART knockdown increased infarct size in the MCAO model, confirming its detrimental effect on ischemic brain injury.
- CART treatment activated ERK 1/2 phosphorylation, while p38 and JNK pathways remained unaffected.
- Neuroprotection by CART was abolished by CART knockdown and ERK antagonists (PD98059, U0126), but not by p38 or JNK antagonists.
Conclusions:
- CART is an endogenous neuroprotective peptide against cerebral ischemia.
- CART mediates its protective effects through the MAPK/ERK signaling pathway.
- CART holds potential as a therapeutic agent for treating stroke-related brain injury.
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