Minocycline treatment inhibits lipid peroxidation, preserves spinal cord ultrastructure, and improves functional outcome after traumatic spinal cord injury in the rat.
METHODS
A prospective, randomized experimental research.


OBJECTIVE
To evaluate the short- and long-term neuroprotective effects of minocycline on the secondary injury process of an experimental traumatic spinal cord injury (SCI) model.


BACKGROUND
Traumatic SCI is a devastating problem of health that results in high morbidity and mortality rates. The loss of function after SCI results from both the primary mechanical insult and the subsequent, multifaceted secondary response.


METHODS
A total of 80 adult male Spraque-Dawley rats (breeded by the Baskent University Animal Research Center) were randomly divided into 4 groups. A T10 contusion injury was produced by using modified Allen technique in all groups except the control group. No medication was administered to the rats in the trauma group. Minocycline was administered intraperitoneally and intravenously to the treatment groups. Short-term and/or long-term neuroprotective effects of minocycline on the lipid peroxidation (malondialdehyde, glutathione), apoptosis (terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling), ultrastructure of spinal cord (tissue electron microscopy), and behavioral assessments (Basso-Beattie-Bresnahan) were evaluated.


RESULTS
As compared with the trauma group, tissue malondialdehyde and glutathione levels demonstrated that minocycline significantly diminishes lipid peroxidation. Electromicroscopic study showed that minocycline preserves the ultrastructure of spinal cord tissue in the early post-traumatic period. Minocycline treatment significantly reduced the number of terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling positive cells both 1 day and 28 days after SCI. Behavioral assessments showed significant improvement in the hind limb functions of minocycline receiving rats starting 7 days after the SCI. Any statistically significant difference was not found between intraperitoneal or intravenous routes for minocycline injection.


CONCLUSIONS
Minocycline is neuroprotective and contributes to functional improvement after traumatic SCI by eliminating the destructive process of secondary injury. Having both satisfying anti-inflammatory and antiapoptotic effects in experimental models, it promises to be of therapeutic use in human SCI.
Department of Neurosurgery, Baskent University School of Medicine, Ankara, Turkey. erkinso@gmail.com
Erkin
E
Sonmez
Serdar
S
Kabatas
Ozlem
O
Ozen
Gulten
G
Karabay
Suna
S
Turkoglu
Ersin
E
Ogus
Cem
C
Yilmaz
Hakan
H
Caner
Nur
N
Altinors
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D006614:Hindlimb / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008911:Minocycline / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology / Q000648:ultrastructure; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D018696:Neuroprotective Agents; D008911:Minocycline