title: Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice.
abstract: BACKGROUND
  Necroptosis is an emerging programmed necrosis other than traditional necrosis and apoptosis. Until recently, there have not been studies that have investigated a relationship between necroptosis and pathogenesis of cell death after spinal cord injury (SCI).
  
  
  OBJECTIVE
  To investigate whether necroptosis takes part in the early pathophysiological processes of traumatic SCI in mice.
  
  
  METHODS
  Female ICR mice were randomized equally into three groups: the sham, the vehicle-treated + SCI group, and the Nec-1-treated + SCI group. To induce SCI, the mice were subjected to a laminectomy at T9 and compression with a vascular clip. After mice were sacrificed 24 hours post-SCI, propidium iodide (PI)-positive cells were detected using in vivo PI labeling. Morphological analyses were performed by hematoxylin and eosin staining and Nissl staining. The samples were evaluated for apoptosis by the in situ TUNEL assay. The expression of caspase-3 was assessed by western blot. Locomotor behavior of hindlimb was evaluated by BMS (Basso mouse scale) score at 1, 3, 5, 7, and 14 days post-injury.
  
  
  RESULTS
  Compared with dimethyl sulfoxide -treated mice, necrostatin-1-treated mice showed decreased PI-positive cells (P < 0.05), alleviated tissue damage, more surviving neuron at 24 hours after SCI (P < 0.05), and improved functional recovery from days 7 to 14 (P < 0.05). Necrostatin-1 did not reduce the expression of caspase-3 and the number of TUNEL-positive cells at 24 hours after SCI (P > 0.05).
  
  
  CONCLUSIONS
  Necroptosis contributes to necroptotic cell death and influences functional outcome after SCI in adult mice. The inhibition of necroptosis by necrostatin-1 may have therapeutic potential for patients with SCI.
authors: Ming
authors: M
authors: Liu
authors: Wei
authors: W
authors: Wu
authors: Hua
authors: H
authors: Li
authors: Song
authors: S
authors: Li
authors: Li-tian
authors: LT
authors: Huang
authors: Yi-qing
authors: YQ
authors: Yang
authors: Qing
authors: Q
authors: Sun
authors: Chun-xi
authors: CX
authors: Wang
authors: Zhuang
authors: Z
authors: Yu
authors: Chun-hua
authors: CH
authors: Hang
mesh_terms: D000818:Animals; D017209:Apoptosis; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008124:Locomotion; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D007093:Imidazoles; D007211:Indoles; D018696:Neuroprotective Agents; C507699:necrostatin-1
keywords: Functional outcome; Necroptosis; Necrostatin-1; Spinal cord injury