Immunization with a Neural-Derived Peptide Protects the Spinal Cord from Apoptosis after Traumatic Injury

Abstract

Apoptosis is one of the most destructive mechanisms that develop after spinal cord (SC) injury. Immunization with neural-derived peptides (INDPs) such as A91 has shown to reduce the deleterious proinflammatory response and the amount of harmful compounds produced after SC injury. With the notion that the aforementioned elements are apoptotic inducers, we hypothesized that INDPs would reduce apoptosis after SC injury. In order to test this assumption, adult rats were subjected to SC contusion and immunized either with A91 or phosphate buffered saline (PBS; control group). Seven days after injury, animals were euthanized to evaluate the number of apoptotic cells at the injury site. Apoptosis was evaluated using DAPI and TUNEL techniques; caspase-3 activity was also evaluated. To further elucidate the mechanisms through which A91 exerts this antiapoptotic effects we quantified tumor necrosis factor-alpha (TNF-α). To also demonstrate that the decrease in apoptotic cells correlated with a functional improvement, locomotor recovery was evaluated. Immunization with A91 significantly reduced the number of apoptotic cells and decreased caspase-3 activity and TNF-α concentration. Immunization with A91 also improved the functional recovery of injured rats. The present study shows the beneficial effect of INDPs on preventing apoptosis and provides more evidence on the neuroprotective mechanisms exerted by this strategy.

Protective effect of geraniol inhibits inflammatory response, oxidative stress and apoptosis in traumatic injury of the spinal cord through modulation of NF-κB and p38 MAPK

“…Apoptosis is a complex pathophysiological process, mainly completed by the protease cascade mediated by caspase family members, in which caspase-3 serves a key role. Caspase-3 belongs to the cysteine-aspartic protease family that is important in the implementation segment of the apoptosis (31). The present study showed that treatment with geraniol significantly weakened the caspase-3 and caspase-9 activities in SCI rats.…”

“…Traumatic SCI is a serious and relatively common injury for which there is no clear and effective approach for treatment (31). Following SCI, necrosis and apoptosis occur in nerve cells and tissues.…”

Effects of active immunisation with myelin basic protein and myelin-derived altered peptide ligand on pain hypersensitivity and neuroinflammation

“…Myelin-derived APLs have been shown to confer beneficial effects in various animal models of autoimmune diseases including EAE (Karin et al, 1994, Tian et al, 2013a, experimental models of spinal cord injury (Rodriguez- Barrera et al, 2013 and peripheral nerve injury (Perera et al, 2015). (Tian et al, 2013a, Gaur et al, 1997, Nicholson et al, 1995, Fischer et al, 2000, Santambrogio et al, 1998, Ruiz et al, 1999, Karin et al, 1994, Brocke et al, 1996.…”

Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands

“…Numerous studies have shown that many neurons die as a consequence of apoptosis. Therefore, regulating apoptotic cell death might play an important role in the neurological recovery following SCI [99,116]. Recent investigations on the field found that immunizing with A91 decreases caspase-3 activity and TNFα concentrations, reducing the number of apoptotic cells, which is directly correlated with functional improvement after injury [100].…”