当前位置： SCI文献检索 > JOURNAL OF NEUROTRAUMA期刊下所有文献 > Pharmacological inhibition of soluble tumor necrosis factor-alpha (sTNFα) 2 weeks after high thoracic spinal cord injury does not affect sympathetic hyperreflexia.

Pharmacological inhibition of soluble tumor necrosis factor-alpha (sTNFα) 2 weeks after high thoracic spinal cord injury does not affect sympathetic hyperreflexia.

Abstract：

:After a severe, high-level spinal cord injury (SCI), plasticity to intraspinal circuits below injury results in heightened spinal sympathetic reflex activity and detrimentally impacts peripheral organ systems. Such sympathetic hyperreflexia is immediately apparent as an episode of autonomic dysreflexia (AD), a life-threatening condition characterized by sudden hypertension and reflexive bradycardia following below-level sensory inputs; for example, pressure sores or impacted fecal matter. Over time, plasticity within the spinal sympathetic reflex (SSR) circuit contributes to the progressive intensification of AD events, as the frequency and severity of AD events increase greatly beginning ∼2 weeks post-injury (wpi). The neuroimmune system has been implicated in driving sympathetic hyperreflexia, as inhibition of the cytokine soluble tumor necrosis factor-alpha (sTNFα) using the biological mimetic XPro1595 beginning within days post-SCI has been shown to attenuate the development of AD. Here, we sought to further understand the effective therapeutic time window of XPro1595 to diminish sympathetic hyperreflexia, as indicated by AD. We delayed the commencement of continuous intrathecal administration of XPro1595 until 2 weeks after a complete, thoracic level 3 injury in adult rats. We examined the severity of colorectal distension-induced AD biweekly. We found that initiation of sTNFα inhibition at 2 wpi does not attenuate the severity or intensification of sympathetic hyperreflexia compared with saline-treated controls. Coupled with previous data from our group, these findings suggest that central sTNFα signaling must be targeted prior to 2 weeks post-SCI in order to decrease sympathetic hyperreflexia.

journal_name

J Neurotrauma

journal_title

Journal of neurotrauma

authors

O'Reilly M,Mironets E,Saltos T,Crowther K,Collyer E,Bethea J,Tom VJ

doi

10.1089/neu.2020.7504

subject

Has Abstract

pub_date

2021-01-04 00:00:00

eissn

0897-7151

issn

1557-9042

pub_type

杂志文章

在线工具

Pharmacological inhibition of soluble tumor necrosis factor-alpha (sTNFα) 2 weeks after high thoracic spinal cord injury does not affect sympathetic hyperreflexia.