Selective protection of gray and white matter during spinal cord ischemic injury.
BACKGROUND
Ischemic injury in the gray matter is associated with excitatory amino acid neurotransmitters (EAA) release, and in the white matter is associated with intracellular sodium accumulation. We investigated the protective effect during spinal ischemia of the EAA antagonist, 2-carboxypiperazinyl-propylphosphonic acid (CPP), and the sodium channel blocker (2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX).


METHODS
Sprague-Dawley rats were randomized in four groups, received intrathecally 10 microL of saline, CPP, QX, or QX/CPP, and underwent balloon occlusion of the aorta. Proximal pressure was lowered by exsanguination. In the acute protocol, 28 rats were used to calculate the length of occlusion, resulting in paraplegia in 50% of animals (P50). In the chronic study, 60 rats underwent 11' occlusion. The chronic animals were scored daily for 28 days and submitted to cord histology.


RESULTS
The P50 of QX (11'22") and QX/CPP (11'54") were longer than saline (10'39"), suggesting a beneficial effect. Neurologic scores of all treatment groups (p = 0.0001) and histologic scores of CPP (p = 0.003) and QX/CPP (p = 0.002) were better than saline.


CONCLUSIONS
Protection of spinal cord during ischemia can be achieved with intrathecal administration of selective agents directed to the gray and white matter.
Follis
F M
FM
Department of Cardiothoracic Surgery, University of New Mexico Health Sciences Center, Albuquerque 87131, USA. follisW@unm.edu
Blisard
K S
KS
Varvitsiotis
P S
PS
Pett
S B
SB
Temes
R T
RT
Wernly
J A
JA
D000818:Animals; D001921:Brain / Q000503:physiopathology; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D007278:Injections, Spinal; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D010264:Paraplegia / Q000517:prevention & control; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000627:therapeutic use; D013116:Spinal Cord / Q000098:blood supply*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; C012647:QX-314; D012965:Sodium Chloride; D008012:Lidocaine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid