PEGylated interferon-beta modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury.
Secondary degeneration leads to an expansion of the initial tissue damage sustained during a spinal cord injury (SCI). Dampening the cellular inflammatory response that contributes to this progressive tissue damage is one possible strategy for neuroprotection after acute SCI. We initially examined whether treatment with a PEGylated form of rat interferon-beta (IFN-beta) would modulate the expression of several markers of inflammation and neuroprotection at the site of a unilateral cervical level 5 contusion injury. Adult female Sprague-Dawley rats were injured using the Infinite Horizon Impactor at a force of 200 kdyn (equivalent to a severe injury) and a mean displacement of 1600-1800 mum. A single dose (5x10(6) units) of PEGylated IFN-beta or vehicle was administered 30 min following SCI. Here we demonstrate temporal changes in pro- and anti-inflammatory cytokine levels and the expression of heat shock proteins and iNOS (involved in neuroprotection) at the lesion epicenter and one segment caudally after SCI and PEG IFN-beta treatment. The results suggested a potential therapeutic treatment strategy for modulation of secondary damage after acute SCI. Therefore, we examined whether acute treatment with PEG IFN-beta would improve forelimb function alone or when combined with forced exercise (Ex). Animals began the Ex paradigm 5 days post SCI and continued for 5 days/week over 8 weeks. Locomotion (forelimb locomotor scale [FLS], hindlimb BBB, and TreadScan) and sensorimotor function (grid walking) was tested weekly. Additional outcome measures included lesion size and glial cell reactivity. Significant FLS improvements occurred at 1 week post SCI in the PEGylated IFN-beta-treated group but not at any other time point or with any other treatment approaches. These results suggest that this acute neuroprotective treatment strategy does not translate into long term behavioral recovery even when combined with forced exercise.
Sandrow-Feinberg
Harra R
HR
Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Zhukareva
Victoria
V
Santi
Lauren
L
Miller
Kassi
K
Shumsky
Jed S
JS
Baker
Darren P
DP
Houle
John D
JD
D000208:Acute Disease; D000818:Animals; D002574:Cervical Vertebrae; D003131:Combined Modality Therapy; D005081:Exercise Therapy; D005260:Female; D005552:Forelimb / Q000294:innervation / Q000502:physiology; D016899:Interferon-beta / Q000276:immunology / Q000494:pharmacology*; D007633:Keratins / Q000097:blood; D008124:Locomotion / Q000187:drug effects; D009187:Myelitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D018696:Neuroprotective Agents / Q000276:immunology / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
D018696:Neuroprotective Agents; D011092:Polyethylene Glycols; D007633:Keratins; D016899:Interferon-beta