NON-activated protein C as post-treatment after spinal cord compression injury in rats.
BACKGROUND
Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI.


METHODS
Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology.


RESULTS
Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week.


CONCLUSIONS
NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.
Petter-Puchner
A H
AH
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology at the Trauma Research Center of the AUVA, Vienna, Austria. alexander.petter@lbitrauma.org
Sieber
J
J
Hopf
R
R
Ohlinger
W
W
Schuller
M
M
Redl
H
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D008297:Male; D010243:Paralysis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D011486:Protein C / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D000925:Anticoagulants; D011486:Protein C