title: Evaluation of time-dependent spread of tissue damage in experimental spinal cord injury by killed-end evoked potential: effect of high-dose methylprednisolone.
abstract: OBJECTIVE
  Histopathological studies on spinal cord injury (SCI) have demonstrated time-dependent spread of tissue damage during the initial several hours postinjury. When the long tract within the spinal cord is stimulated, a large monophasic positivity occurs at the injury site. This type of potential, termed the killed-end evoked potential (KEEP), indicates that a nerve impulse approaches but does not pass beyond the injury site. The authors tested the hypothesis that the damage spread can be evaluated as a progressive shift of the KEEP on a real-time basis. The effect of high-dose methylprednisolone sodium succinate (MPSS) on the spread of tissue damage was also examined by this methodology.
  
  
  METHODS
  The KEEP was recorded using an electrode array placed on the spinal cord at the T-10 level in cats. This electrode array consisted of multiple 0.2-mm-diameter electrodes, each separated by 0.5 mm. Spinal cord injury was induced using a vascular clip (65 g pinching pressure for 30 seconds). The midline posterior surface of the spinal cord was stimulated bipolarly at the C-7 level by applying a single pulse at supramaximal intensity. During the initial period of 6 hours postinjury, the localization of the largest KEEP shifted progressively up to 2.5 mm rostral from the injury site. The amplitude of the KEEP recorded at the injury site decreased to 55 to 70% and became slightly shortened in latency as the localization of the largest KEEP shifted rostrally. These findings imply that the injury site KEEP represents the volume-conducted potential of the largest KEEP at the site of the conduction block. It moved away from the injury site in association with the damage spread, and this was confirmed histopathologically. A decrease in amplitude of KEEP at the injury site appeared to be the most sensitive measure of the damage spread, because the amplitude of the volume-conducted KEEP is inversely proportional to the square of the distance between the recording site and site of conduction block. Administered immediately after SCI, MPSS clearly inhibited these events, especially within 30 minutes postinjury.
  
  
  CONCLUSIONS
  The KEEP enables sequential evaluation to be made of the time-dependent spread of tissue damage in SCI in the same animal. It is, therefore, useful for detecting the effect of therapeutic interventions and for determining the therapeutic time window. The efficiency of MPSS to inhibit the spread of damaged tissue appeared to be maximized when it was administered within the initial 30-minute period postinjury.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan. chikashi@tb3.so-net.ne.jp
authors.forename: Chikashi
authors.initials: C
authors.lastname: Fukaya
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kasai
authors.forename: Jun
authors.initials: J
authors.lastname: Kurihara
authors.forename: Sadahiro
authors.initials: S
authors.lastname: Maejima
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005071:Evoked Potentials; D008775:Methylprednisolone / Q000494:pharmacology*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D008775:Methylprednisolone