Spatial and temporal correlation in progressive degeneration of neurons and astrocytes in contusion-induced spinal cord injury.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Loss of astrocyte function may be more critical for delayed neuronal death than microglial activation and monocyte infiltration.
Department of Pharmacology, Ajou University School of Medicine, san-5 Woncheon-dong Youngtong-gu, Suwon, Kyunggi-do, 442-721, Korea.
Kyoung-Jin
KJ
Min
Hey-Kyeong
HK
Jeong
Beomsue
B
Kim
Dong Hoon
DH
Hwang
Hae Young
HY
Shin
An Tran
AT
Nguyen
Jong-Hyeon
JH
Kim
Ilo
I
Jou
Byung G
BG
Kim
Eun-Hye
EH
Joe
D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis; D003288:Contusions / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D008840:Microfilament Proteins / Q000096:biosynthesis; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins