Lipopolysaccharide preconditioning attenuates apoptotic processes and improves neuropathologic changes after spinal cord injury in rats

Abstract

We have shown earlier that administration of low-dose lipopolysaccharide (LPS) significantly contributed to recovery of motor function after traumatic spinal cord injury in the adult female rat. Using the same standardized animal model, we have now designed a set of experiments to test the hypothesis that LPS preconditioning attenuates stress-related apoptotic processes early after spinal cord trauma. The lower thoracic spinal cord injury in adult female Sprague-Dawley rats was caused by a 10 g weight rod drop from 25 mm on the dural surface of the exposed spinal cord at T10. The rats were randomly assigned to three groups: Sham injury, control (received normal saline alone), and LPS preconditioning (0.2 mg/kg, ip; 72 h prior to the injury). The animals were euthanized at 72 h postinjury. Neuropathologic changes were assessed using hematoxylin and eosin staining. SCI-induced apoptosis were observed by transmission electron microscopy. Caspase-3, cleaved caspase-3, Bax, and Bcl-2 were examined with immunohistochemistry or Western blotting. Compared with the control group, LPS preconditioning group showed significant improvement in the SCI-induced morphology changes. Furthermore, LPS preconditioning reduced the expressions of apoptotic markers caspase-3, cleaved caspase-3, and Bax, upregulated the expression of antiapoptotic marker Bcl-2 in the samples of spinal cord. Low-dose LPS attenuated the recruitment of inflammatory cells and the proliferation of glial cells in the site of injury. LPS preconditioning has neuroprotective effects against TSCI in rats due to its antiapoptosis properties as shown by the inhibition of caspase pathway and the upregulation of antiapoptotic protein.

Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

“…The concept of inflammatory preconditioning is new. It has been previously evaluated only recently in ischemic stroke [41] or spinal cord injury [26], but not in SAH. Here, we show marked effects on inflammation itself and the consecutive downstream pathways.…”

“…Here, TLR4-signaling and its possible alteration via preconditioning might play an important role [22,23]. Inflammatory preconditioning has also been investigated in contexts of inflammation after stroke or spinal cord injury where neuroprotective effects have been shown [24][25][26].…”

Serial Systemic Injections of Endotoxin (LPS) Elicit Neuroprotective Spinal Cord Microglia through IL-1-Dependent Cross Talk with Endothelial Cells

“…In spinal cord, the benefits of LPS preconditioning have been described only in the context of traumatic SCI (Hayakawa et al, 2014;Li et al, 2014Li et al, , 2016. Because traumatic SCI cannot be predicted, preconditioning is of little clinical value in this context.…”

Mitigating effect of tanshinone IIA on ventricular remodeling in rats with pressure overload-induced heart failure

“…The myocardial tissue was homogenized, and the protein was extracted. The expressions levels of cardiomyocyte apoptosis-related proteins including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X (Bax) and cleaved cysteinyl aspartate specific proteinase-3 (cleaved caspase-3) were determined using western blotting assays 15 . The procedures were in accordance to the instructions of kits (Shanghai Yanjie Biotechnology Co., Ltd., Shanghai, China).…”