Tissue and Cell 40 (2008) 143–156
Contuse lesion of the rat spinal cord of moderate intensity leads to a
higher time-dependent secondary neurodegeneration than severe one
An open-window for experimental neuroprotective interventions
, F.R. Hanania, K. Daci, R.J.A. Leme, G. Chadi
Neuroregeneration Center, Experimental Neurology, Department of Neurology, University of S˜ao Paulo School of Medicine,
Av. Dr. Arnaldo, 455, CEP: 01246-903, S˜ao Paulo, Brazil
Received 16 August 2007; received in revised form 12 November 2007; accepted 14 November 2007
Available online 18 January 2008
Secondary neurodegeneration takes place in the surrounding tissue of spinal cord trauma and modiﬁes substantially the prognosis, consid-
ering the small diameter of its transversal axis. We analyzed neuronal and glial responses in rat spinal cord after different degree of contusion
promoted by the NYU Impactor. Rats were submitted to vertebrae laminectomy and received moderate or severe contusions. Control animals
were sham operated. After 7 and 30 days post surgery, stereological analysis of Nissl staining cellular proﬁles showed a time progression of the
lesion volume after moderate injury, but not after severe injury. The number of neurons was not altered cranial to injury. However, same degree
of diminution was seen in the caudal cord 30 days after both severe and moderate injuries. Microdensitometric image analysis demonstrated a
microglial reaction in the white matter 30 days after a moderate contusion and showed a widespread astroglial reaction in the white and gray
matters 7 days after both severities. Astroglial activation lasted close to lesion and in areas related to Wallerian degeneration. Data showed a
more protracted secondary degeneration in rat spinal cord after mild contusion, which offered an opportunity for neuroprotective approaches.
Temporal and regional glial responses corroborated to diverse glial cell function in lesioned spinal cord.
© 2007 Elsevier Ltd. All rights reserved.
Keywords: Spinal cord injury; Secondary degeneration; Astrocyte; Microglia; NYU Impactor; Stereological quantiﬁcation
Traumatic injury to central nervous system triggers a
protracted secondary degeneration, which accentuates tissue
damage at and beyond the original site of trauma (Dusart and
Schwab, 1994; Hill et al., 2001). This phenomenon may mod-
ify substantially the prognosis of a particular partial lesion in
the spinal cord, considering the small transversal dimension
of the organ. Secondary injury in spinal cord after a con-
tuse lesion leads to an inﬂammatory response which involves
ischemia, edema, increased excitatory amino acids and tissue
Corresponding author. Tel.: +55 11 3061 7460.
E-mail address: firstname.lastname@example.org (G. Chadi).
Present address: School of Arts, Sciences and Humanities, Av. Arlindo
Bettio, 1000, Room 237, Ermelino Matarazzo, CEP: 03828-000, S
Brazil. Tel.: +55 11 30911008.
damage from reactive oxygen species (Carlson et al., 1998;
Popovich et al., 1999). As a result, a typical picture of destruc-
tion of the cord center and chronic sparing of a peripheral rim
of ﬁbers takes place.
A standardized model of contuse rat spinal cord injury has
been used to promote different lesions’ intensities. The New
York University (NYU) Impactor was developed in conjunc-
tion with a consortium of investigators seeking to provide
coordinated preclinical examination of spinal cord injury
therapies (the Multicenter Animal Spinal Cord Injury Study
or MASCIS). It has been deﬁned that the contuse lesions
promoted by the Impactor exhibit a progressive secondary
expansion and produce a long-term expression of cell death
by apoptosis in the spinal cord cells including neurons and
oligodendrocytes (Abe et al., 1999; Warden et al., 2001).
Different levels of injuries and of postoperative survival
times were aimed for describing the patterns of degenera-
0040-8166/$ – see front matter © 2007 Elsevier Ltd. All rights reserved.