Mechanisms of improvement following functional inhibition of neutrophil infiltration after spinal cord injury

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Spinal Cord Injury (SCI) is a traumatic event that results in loss of function below the level of injury, and other dysfunctions including pain syndromes, both above and below the level of the lesion. A cascade of biochemical and cellular events leads to secondary events after SCI, exacerbating the injury, and contributes to loss of tissue and increased dysfunctions. While thought to be beneficial, inflammation induced by trauma in the spinal cord contributes to secondary injury early in SCI. Thus, in this project a mammalian model is used to investigate a targeted anti-inflammatory treatment for SCI, and compare it with the current standard therapy of high dose methylprednisolone (MPSS).\r\nTo ensure that the new generation of devices used in experimental SCI can reliably produce an injury that parallels the outcomes seen in the clinical setting, we characterized a rodent model of SCI by adjusting several mechanical parameters of the device. Injuries with higher force or increased duration of compression increased sensitivity to mechanical stimuli and produced loss of locomotion and loss of bladder function, syndromes seen clinically after SCI.\r\nTreatment after SCI with recombinant neutrophil inhibitory factor (rNIF) was tested to determine if inhibition of neutrophils, a primary inflammatory cell, in the first 24 hours after injury would improve outcome measures. Treatment with rNIF reduced neutrophil infiltration after injury by greater than 50% and resulted in decreased sensitivity to mechanical stimuli and improved bladder function. Additionally, the amount of white and grey matter lost secondary to SCI was reduced.\r\nSince neutrophils release proteinases, generate reactive oxygen species, phagocytize cells and influence inflammatory cytokine expression, pro- and anti-inflammatory cytokine protein levels were measured at specific time points after SCI, in both the spinal parenchyma and blood serum. Treatment with rNIF had a significant effect on cytokine expression after injury.\r\nThese results demonstrate the effectiveness of inhibiting secondary injury after SCI using rNIF and one mechanism for improved outcomes may be the altered the expression pattern of pro- and anti-inflammatory cytokines which may contribute to dysfunctional outcomes after SCI.\r\n

spinal cord injury, neutrophils, neuropathic pain, inflammation