Ischemic Preconditioning in White Matter: Magnitude and Mechanism.
Margaret A HamnerZucheng YeRichard V LeeJamie R ColmanThu LeDavin C GongBruce R RansomJonathan R WeinsteinPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
Ischemic preconditioning (IPC) has been studied predominantly in gray matter, but stroke in humans frequently involves white matter (WM) as well. Here we describe a novel, combined in vivo/ex vivo mouse model to determine whether IPC occurs in WM. It does. Using genetically altered mice, we identified two innate immune cell receptors, Toll-like receptor 4 and type 1 interferon receptor (IFNAR1), that are required for IPC-mediated protection in WM. Furthermore, using microglia-targeted IFNAR1 knockdown, we demonstrate that interferon signaling specifically in microglia is essential for this protection. The discovery of IPC as an intrinsic capability of WM is novel and important. This is also the first in vivo demonstration that cell-type-specific expression of an individual gene plays an indispensable role in IPC-mediated protection.
Keyphrases
- white matter
- toll like receptor
- inflammatory response
- cerebral ischemia
- ischemia reperfusion injury
- immune response
- mouse model
- nuclear factor
- multiple sclerosis
- dendritic cells
- small molecule
- poor prognosis
- subarachnoid hemorrhage
- atrial fibrillation
- blood brain barrier
- genome wide
- brain injury
- cancer therapy
- oxidative stress
- binding protein
- drug delivery
- gene expression
- transcription factor