Journal of neurotrauma
-
Journal of neurotrauma · Aug 2019
Noninvasive quantification of axonal loss in the presence of tissue swelling in traumatic spinal cord injury mice.
Neuroimaging plays an important role in assessing axonal pathology after traumatic spinal cord injury. However, coexisting inflammation confounds imaging assessment of the severity of axonal injury. Herein, we applied diffusion basis spectrum imaging (DBSI) to quantitatively differentiate and quantify underlying pathologies in traumatic spinal cord injury at 3 days post-injury. ⋯ DBSI was able to detect and quantify axonal loss in the presence of white matter tract swelling. The DBSI-defined apparent axonal volume correlated with the corresponding histological markers. DBSI-derived pathological metrics could serve as neuroimaging biomarkers to differentiate and quantify coexisting white matter pathologies in spinal cord injury, providing potential surrogate outcome measures to assess spinal cord injury progression and response to therapies.
-
Journal of neurotrauma · Aug 2019
Endogenous Interleukin-10 Deficiency Exacerbates Vascular Pathology in Traumatic Cervical Spinal Cord Injury.
Although the majority of traumatic spinal cord injuries (SCIs) take place at the cervical level, pre-clinical studies have been disproportionally focused on thoracic insults. With differences in anatomy, physiology, and immune response between spinal cord levels, there is evidence that injury pathophysiology may vary, requiring tailored treatment paradigms. Further, as only a few therapies have been successfully translated to the clinic, cervical models are increasingly recognized as essential for the characterization of trauma and therapy. ⋯ Here, using in vivo high-resolution ultrasound imaging, we demonstrate that IL-10 deficiency is associated with increased acute vascular damage. Importantly, the loss of endogenous IL-10 led to significant differences in the acute systemic response to SCI, specifically the circulating levels of IL-12 (p70), LIX (CXCL5), IL-1β, tumor necrosis factor (TNF)-α, and IL-6 relative to genotype sham controls. These effects also fostered modest impairments in long-term functional recovery, assessed by the Basso Mouse Scale, as well as histological outcomes.
-
Journal of neurotrauma · Aug 2019
Effect of differently polarized macrophages on proliferation and differentiation of ependymal cells from adult spinal cord.
Ependymal cells (EpCs) are a kind of multi-potent stem cells in the central canal of adult spinal cord, which proliferate following spinal cord injury (SCI). Although they can differentiate into functional neurons in vitro, EpC progeny differentiate mainly into astrocytes after SCI, and the mechanism remains unclear. The present study aimed to explore whether neuroinflammation induced by classically activated macrophages (M1) or alternatively activated macrophages (M2) had an effect on EpC proliferation and/or differentiation. ⋯ Co-culture in M2 conditioned medium obviously increased the proportion of βIII-tubulin-positive cells (p < 0.01). Small amounts of MAP2-positive neurons could be detected on day 7 in the M2 group and the control group. M1 conditioned medium could promote EpC proliferation in response to SCI through the TNFα-MAPK-Sox2 signaling pathway; M2 conditioned medium favors EpCs differentiating toward neurons.
-
Journal of neurotrauma · Aug 2019
Differential expression profiles and functional predication of circRNA in traumatic spinal cord injury of rats.
Recent studies indicate that circular ribonucleic acids (circRNAs) are involved in a variety of human diseases. The roles of circRNAs in traumatic spinal cord injury (SCI) remain unknown, however. We performed RNA-seq to analyze the circRNA expression profile in rat spinal cord after SCI and to investigate the relevant mechanisms. ⋯ In addition, the expression levels of six selected circRNAs were verified successfully by quantitative real-time polymerase chain reaction. Further study identified circRNA_07079 and circRNA_01282 as being associated with SCI, and they may participate in the pathophysiology of SCI through circRNA-targeted miRNA-messenger RNA axis. In summary, the results of our study revealed the expression profiles and potential functions of differentially expressed circRNAs in traumatic SCI in rats; this may provide new clues for studying the mechanisms underlying SCI and also present novel molecular targets for clinical therapy of SCI.
-
Journal of neurotrauma · Aug 2019
Sexual Dimorphism of Pain Control: Analgesic Effects of Pioglitazone and Azithromycin in Chronic Spinal Cord Injury.
Central neuropathic pain develops in greater than 75% of individuals suffering a spinal cord injury (SCI). Increasingly, sex is recognized as an important biological variable in the development and treatment of peripheral neuropathic pain, but much less is known about the role of sex in central neuropathic pain and its pharmacological inhibition. To test the hypothesis that efficacy of analgesic therapies differs between males and females in SCI, we used a mouse model of SCI pain to determine the analgesic efficacy of pioglitazone (PIO), U. ⋯ We observed a sex-specific effect of PIO with significant antihyperalgesic effects in females, but not males. In contrast, AZM was effective in both sexes. Our data support the use of PIO and AZM as novel therapies for SCI pain and highlight the importance of considering sex as a biological variable in clinical and experimental SCI pain research.