The relationship between localized subarachnoid inflammation and parenchymal pathophysiology after spinal cord injury.
Subarachnoid inflammation following spinal cord injury (SCI) can lead to the formation of localized subarachnoid scarring and the development of post-traumatic syringomyelia (PTS). While PTS is a devastating complication of SCI, its relative rarity (occurring symptomatically in about 5% of clinical cases), and lack of fundamental physiological insights, have led us to examine an animal model of traumatic SCI with induced arachnoiditis. We hypothesized that arachnoiditis associated with SCI would potentiate early parenchymal pathophysiology. To test this theory, we examined early spatial pathophysiology in four groups: (1) sham (non-injured controls), (2) arachnoiditis (intrathecal injection of kaolin), (3) SCI (35-g clip contusion/compression injury), and (4) PTS (intrathecal kaolin+SCI). Overall, there was greater parenchymal inflammation and scarring in the PTS group relative to the SCI group. This was demonstrated by significant increases in cytokine (IL-1α and IL-1β) and chemokine (MCP-1, GRO/KC, and MIP-1α) production, MPO activity, blood-spinal cord barrier (BSCB) permeability, and MMP-9 activity. However, parenchymal inflammatory mediator production (acute IL-1α and IL-1β, subacute chemokines), BSCB permeability, and fibrous scarring in the PTS group were larger than the sum of the SCI group and arachnoiditis group combined, suggesting that arachnoiditis does indeed potentiate parenchymal pathophysiology. Accordingly, these findings suggest that the development of arachnoiditis associated with SCI can lead to an exacerbation of the parenchymal injury, potentially impacting the outcome of this devastating condition.
Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
James W
JW
Austin
Mehdi
M
Afshar
Michael G
MG
Fehlings
D000818:Animals; D001099:Arachnoid / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D001100:Arachnoiditis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D009187:Myelitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000473:pathology / Q000503:physiopathology*