title: X-ray microbeam irradiation of the contusion-injured rat spinal cord temporarily improves hind-limb function.
abstract: Spinal cord injury is a devastating condition with no effective treatment. The physiological processes that impede recovery include potentially detrimental immune responses and the production of reactive astrocytes. Previous work suggested that radiation treatment might be beneficial in spinal cord injury, although the method carries risk of radiation-induced damage. To overcome this obstacle we used arrays of parallel, synchrotron-generated X-ray microbeams (230 μm with 150 μm gaps between them) to irradiate an established model of rat spinal cord contusion injury. This technique is known to have a remarkable sparing effect in tissue, including the central nervous system. Injury was induced in adult female Long-Evans rats at the level of the thoracic vertebrae T9-T10 using 25 mm rod drop on an NYU Impactor. Microbeam irradiation was given to groups of 6-8 rats each, at either Day 10 (50 or 60 Gy in-beam entrance doses) or Day 14 (50, 60 or 70 Gy). The control group was comprised of two subgroups: one studied three months before the irradiation experiment (n = 9) and one at the time of the irradiations (n = 7). Hind-limb function was blindly scored with the Basso, Beattie and Bresnahan (BBB) rating scale on a nearly weekly basis. The scores for the rats irradiated at Day 14 post-injury, when using t test with 7-day data-averaging time bins, showed statistically significant improvement at 28-42 days post-injury (P < 0.038). H&E staining, tissue volume measurements and immunohistochemistry at day ≈ 110 post-injury did not reveal obvious differences between the irradiated and nonirradiated injured rats. The same microbeam irradiation of normal rats at 70 Gy in-beam entrance dose caused no behavioral deficits and no histological effects other than minor microglia activation at 110 days. Functional improvement in the 14-day irradiated group might be due to a reduction in populations of immune cells and/or reactive astrocytes, while the Day 10/Day 14 differences may indicate time-sensitive changes in these cells and their populations. With optimizations, including those of the irradiation time(s), microbeam pattern, dose, and perhaps concomitant treatments such as immunological intervention this method may ultimately reach clinical use.
authors.affiliation: Medical Department, Brookhaven National Laboratory, Upton, New York, USA. avraham.dilmanian@stonybrook.edu
authors.forename: F Avraham
authors.initials: FA
authors.lastname: Dilmanian
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Jenkins
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhong
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Park
authors.forename: Nicolle R
authors.initials: NR
authors.lastname: Desnoyers
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sobotka
authors.forename: Giovanna R
authors.initials: GR
authors.lastname: Fois
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Messina
authors.forename: Marjorie
authors.initials: M
authors.lastname: Morales
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hurley
authors.forename: Leeann
authors.initials: L
authors.lastname: Trojanczyk
authors.forename: Saffa
authors.initials: S
authors.lastname: Ahmad
authors.forename: Neda
authors.initials: N
authors.lastname: Shahrabi
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Coyle
authors.forename: Allen G
authors.initials: AG
authors.lastname: Meek
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000818:Animals; D003288:Contusions / Q000150:complications*; D005260:Female; D006614:Hindlimb / Q000503:physiopathology* / Q000528:radiation effects*; D009010:Monte Carlo Method; D011879:Radiotherapy Dosage; D051381:Rats; D020318:Rats, Long-Evans; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000532:radiotherapy*; D017356:Synchrotrons; D013997:Time Factors; D014964:X-Ray Therapy / Q000295:instrumentation / Q000379:methods*