Abstract | BACKGROUND:
Stroke is the primary cause of long-term disability in the United States. Interestingly, mounting evidence has suggested potential sex differences in the response to stroke treatment in patients as, at least in part, distinct cell death programs may be triggered in females and males following stroke. The NIH has recognized that females are strikingly under-represented in pre-clinical trials. Calcium/calmodulin-dependent protein kinase kinase ( CaMKK) is a major kinase that is activated by elevated intracellular calcium. It has recently been suggested that CaMKK and CaMK IV, a downstream target molecule, are neuroprotective in stroke in males. In this study, we examined stroke outcomes in ovariectomized CaMKK β and CaMK IV deficient females. Cell death/survival signaling and inflammatory responses were assessed. RESULTS: CONCLUSIONS: Inhibition of CaMKK signaling exacerbated stroke outcome and increased BBB impairment, transcriptional inactivation and inflammatory responses in females after stroke. Therefore, CaMKK signaling may be a potential target for stroke treatment in both males and females.
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Authors | Lin Liu, Louise McCullough, Jun Li |
Journal | BMC neuroscience
(BMC Neurosci)
Vol. 15
Pg. 118
(Oct 21 2014)
ISSN: 1471-2202 [Electronic] England |
PMID | 25331941
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Calcium-Calmodulin-Dependent Protein Kinase Kinase
- Calcium-Calmodulin-Dependent Protein Kinase Type 4
- Camk4 protein, mouse
- Camkk2 protein, mouse
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Topics |
- Animals
- Blood-Brain Barrier
(physiopathology)
- Brain
(pathology, physiopathology)
- Brain Ischemia
(pathology, physiopathology)
- Calcium-Calmodulin-Dependent Protein Kinase Kinase
(deficiency, genetics)
- Calcium-Calmodulin-Dependent Protein Kinase Type 4
(deficiency, genetics)
- Cerebral Hemorrhage
(pathology, physiopathology)
- Disease Models, Animal
- Female
- Infarction, Middle Cerebral Artery
- Male
- Mice, Inbred C57BL
- Mice, Knockout
- Ovariectomy
- Severity of Illness Index
- Sex Characteristics
- Stroke
(pathology, physiopathology)
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