Administration of low intensity vibration and a RANKL inhibitor, alone or in combination, reduces bone loss after spinal cord injury-induced immobilization in rats.

We previously reported an ability of low-intensity vibration (LIV) to improve selected biomarkers of bone turnover and gene expression and reduce osteoclastogenesis but lacking of evident bone accrual. In this study, we demonstrate that a prolonged course of LIV that initiated at 2 weeks post-injury and continued for 8 weeks can protect against bone loss after SCI in rats. LIV stimulates bone formation and improves osteoblast differentiation potential of bone marrow stromal stem cells while inhibiting osteoclast differentiation potential of marrow hematopoietic progenitors to reduce bone resorption.

Astrogliosis involves activation of retinoic acid-inducible gene-like signaling in the innate immune response after spinal cord injury.

Spinal cord injury (SCI) induces a glial response in which astrocytes become activated and produce inflammatory mediators. The molecular basis for regulation of glial-innate immune responses remains poorly understood. Here, we examined the activation of retinoic acid-inducible gene (RIG)-like receptors (RLRs) and their involvement in regulating inflammation after SCI.

Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury.

The activation of oxidative damage, neuroinflammation, and mitochondrial dysfunction has been implicated in secondary pathomechanisms following spinal cord injury (SCI). These pathophysiological processes lead to cell death and are tightly regulated by nuclear factor E2-related factor 2/antioxidant response element (Nrf2/ARE) signaling. Here, we investigated whether activation of Nrf2/ARE is neuroprotective following SCI.

Neuroprotective effects of bone morphogenetic protein 7 (BMP7) treatment after spinal cord injury.

Bone morphogenetic protein 7 (BMP7) has been shown to ameliorate reduced dendritic growth induced by glutamate excitotoxicity in neuronal tissue cultures and/or provide an enhancement of functional recovery in central nervous system (CNS) injury. BMP7 expression is modulated by spinal cord injury (SCI), but the molecular mechanisms involved in neuroprotection have not been clearly defined. Here, we show that BMP7 treatment of rats subjected to mild cervical SCI significantly increased the pro-survival mitogen-activated protein kinase-38 (MAPK-38) pathway and levels of N-methyl-D-aspartate receptor 1 (NMDAR-1) resulting in a significant increase in neuronal sparing in the ventral horn of the spinal cord.

A molecular platform in neurons regulates inflammation after spinal cord injury.

Vigorous immune responses are induced in the immune privileged CNS by injury and disease, but the molecular mechanisms regulating innate immunity in the CNS are poorly defined. The inflammatory response initiated by spinal cord injury (SCI) involves activation of interleukin-1beta (IL-1beta) that contributes to secondary cell death. In the peripheral immune response, the inflammasome activates caspase-1 to process proinflammatory cytokines, but the regulation of trauma-induced inflammation in the CNS is not clearly understood.

FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury.

The Fas/CD95 receptor-ligand system plays an essential role in apoptosis that contributes to secondary damage after spinal cord injury (SCI), but the mechanism regulating the efficiency of FasL/Fas signaling in the central nervous system (CNS) is unknown. Here, FasL/Fas signaling complexes in membrane rafts were investigated in the spinal cord of adult female Fischer rats subjected to moderate cervical SCI and sham operation controls. In sham-operated animals, a portion of FasL, but not Fas was present in membrane rafts.

The pathology of human spinal cord injury: defining the problems.

This article reviews the pathology of human spinal cord injury (SCI), focusing on potential differences between humans and experimental animals, as well as on aspects that may have mechanistic or therapeutic relevance. Importance is placed on astrocyte and microglial reactions. These cells carry out a myriad of functions and we review the evidence that supports their beneficial or detrimental effects.