Neural circuit mechanisms underlying aberrantly prolonged functional hyperemia in young Alzheimer's disease mice.

Neurovascular defects are one of the most common alterations in Alzheimer's disease (AD) pathogenesis, but whether these deficits develop before the onset of amyloid beta (Aβ) accumulation remains to be determined. Using in vivo optical imaging in freely moving mice, we explored activity-induced hippocampal microvascular blood flow dynamics in App knock-in and J20 mouse models of AD at early stages of disease progression. We found that prior to the onset of Aβ accumulation, there was a pathologically elevated blood flow response to context exploration, termed functional hyperemia.

Evolving Clinical-Translational Investigations of Cerebroprotection in Ischemic Stroke.

Ischemic stroke is a highly morbid disease, with over 50% of large vessel stroke (middle cerebral artery or internal carotid artery terminus occlusion) patients suffering disability despite maximal acute reperfusion therapy with thrombolysis and thrombectomy. The discovery of the ischemic penumbra in the 1980s laid the foundation for a salvageable territory in ischemic stroke. Since then, the concept of neuroprotection has been a focus of post-stroke care to (1) minimize the conversion from penumbra to core irreversible infarct, (2) limit secondary damage from ischemia-reperfusion injury, inflammation, and excitotoxicity and (3) to encourage tissue repair.

The transcription factor C/EBPβ promotes vascular endothelial growth factor A expression and neural stem cell expansion.

The bZIP transcription factor CCAAT-enhancer-binding protein β (C/EBPβ) exhibits neurogenic, neuritogenic, and pro-survival effects in the central nervous system. Here, we show that C/EBPβ regulates neural stem cell (NSC) expansion and vascular endothelial growth factor A (VEGF-A) level by acting on a C/EBPβ-responsive element within the Vegf-a promoter. As predicted, C/EBPβ depletion reduced VEGF-A production, NSC number, and average neurosphere size in proliferating cultures.

The MAP Kinase Phosphatase MKP-1 Modulates Neurogenesis via Effects on BNIP3 and Autophagy.

Inherited and acquired defects in neurogenesis contribute to neurodevelopmental disorders, dysfunctional neural plasticity, and may underlie pathology in a range of neurodegenerative conditions. Mitogen-activated protein kinases (MAPKs) regulate the proliferation, survival, and differentiation of neural stem cells. While the balance between MAPKs and the family of MAPK dual-specificity phosphatases (DUSPs) regulates axon branching and synaptic plasticity, the specific role that DUSPs play in neurogenesis remains unexplored.

Effects of 9-t-butyl doxycycline on the innate immune response to CNS ischemia-reperfusion injury.

Cerebral ischemia triggers a cascade of neuroinflammatory and peripheral immune responses that contribute to post-ischemic reperfusion injury. Prior work conducted in CNS ischemia models underscore the potential to harness non-antibiotic properties of tetracycline antibiotics for therapeutic benefit. In the present study, we explored the immunomodulatory effects of the tetracycline derivative 9-tert-butyl doxycycline (9-TB) in a mouse model of transient global ischemia that mimics immunologic aspects of the post-cardiac arrest syndrome.