Spatial and temporal correlation in progressive degeneration of neurons and astrocytes in contusion-induced spinal cord injury
- Equal contributors
1 Department of Pharmacology, Ajou University School of Medicine, san-5 Woncheon-dong Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea
2 Neuroscience Graduate Program, Ajou University School of Medicine, Suwon, Korea
3 Institute for Medical Sciences, Ajou University School of Medicine, Suwon, Korea
4 Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea
5 Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon, 442-721, Korea
Journal of Neuroinflammation 2012, 9:100 doi:10.1186/1742-2094-9-100Published: 25 May 2012
Traumatic spinal cord injury (SCI) causes acute neuronal death followed by delayed secondary neuronal damage. However, little is known about how microenvironment regulating cells such as microglia, astrocytes, and blood inflammatory cells behave in early SCI states and how they contribute to delayed neuronal death.
We analyzed the behavior of neurons and microenvironment regulating cells using a contusion-induced SCI model, examining early (3–6 h) to late times (14 d) after the injury.
At the penumbra region close to the damaged core (P1) neurons and astrocytes underwent death in a similar spatial and temporal pattern: both neurons and astrocytes died in the medial and ventral regions of the gray matter between 12 to 24 h after SCI. Furthermore, mRNA and protein levels of transporters of glutamate (GLT-1) and potassium (Kir4.1), functional markers of astrocytes, decreased at about the times that delayed neuronal death occurred. However, at P1 region, ramified Iba-1+ resident microglia died earlier (3 to 6 h) than neurons (12 to 24 h), and at the penumbra region farther from the damaged core (P2), neurons were healthy where microglia were morphologically activated. In addition, round Iba-1/CD45-double positive monocyte-like cells appeared after neurons had died, and expressed phagocytic markers, including mannose receptors, but rarely expressed proinflammatory mediators.
Loss of astrocyte function may be more critical for delayed neuronal death than microglial activation and monocyte infiltration.