title: An efficient device to experimentally model compression injury of mammalian spinal cord.
abstract: We report an efficient and effective device to reproducibly model clinically relevant spinal cord injury (SCI) via controlled mechanical compression. In the present study, following skin incision, dorsal laminectomy was performed to expose T10 spinal cord of adult female Sprague-Dawley rats (230-250 g). The vertebral column was suspended and stabilized by Allis clamps at T8 and 12 spinous processes. A metal impounder was then gently loaded onto T10 dura (20, 35 or 50 g × 5 min; n=7/group), resulting in acute mild, moderate, or severe standing weight compression, respectively. Neurobehavioral outcomes were evaluated using the BBB locomotor scale and inclined plane test for coordinated hindlimb function, and a battery of spinal reflex tests for sensorimotor functions, at 1 day following SCI and weekly thereafter for 7 weeks. Quantitative histopathology was used to assess injury-triggered loss of white matter, gray matter and ventral horn motor neurons. Immunocytochemical levels of glial fibrillary acidic protein (GFAP) and β-amyloid precursor protein (APP) at the cervical and lumbar regions were measured to determine the distal segment impact of T10 compression. The data demonstrates that the standardized protocol generates weight-dependent hindlimb motosensory deficits and neurodegeneration primarily at and near the lesion epicenter. Importantly, there are significantly increased GFAP and APP expressions in spinal cord segments involved in eliciting post-SCI allodynia. Therefore, the described system reliably produces compression trauma in manners partially emulating clinical quasi-static insults to the spinal cord, providing a pragmatic model to investigate pathophysiological events and potential therapeutics for compression SCI.
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Ropper
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Anderson
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: Dou
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: InBo
authors.initials: I
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA.
authors.forename: Hariprakash
authors.initials: H
authors.lastname: Haragopal
authors.affiliation: Department of Neurosurgery, Harvard Medical School/Brigham and Women's Hospital, Boston, MA 02115, USA; Division of SCI Research, Veteran Affairs Boston Healthcare System, Boston, MA 02130, USA; Department of Physical Medicine & Rehabilitation, Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, MA 02114, USA. Electronic address: yang_teng@hms.harvard.edu.
authors.forename: Yang D
authors.initials: YD
authors.lastname: Teng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006614:Hindlimb / Q000503:physiopathology; D007249:Inflammation / Q000209:etiology; D007796:Laminectomy / Q000295:instrumentation / Q000379:methods; D009186:Myelin Sheath / Q000473:pathology; D011597:Psychomotor Performance / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex; D013117:Spinal Cord Compression / Q000473:pathology* / Q000503:physiopathology*; D013997:Time Factors
keywords: Compression; Disk herniation; Histopathology; Inflammation; Locomotion; Pain; Quasi-static; Spinal cord injury; Spinal reflex