Nanomedicine strategies for treatment of secondary spinal cord injury

Abstract

Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly. Unfortunately, the delivery of effective therapeutics is quite limited. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Incorporating nanomedicine into the treatment of neuronal injury and disease would likely push nanomedicine into a new light. This review highlights the various pathological issues involved in secondary spinal cord injury, current treatment options, and the improvements that could be made using a nanomedical approach.

Keywords: acrolein; drug delivery; methylprednisolone; secondary injury; spinal cord injury.

Figure 1

Common reactive oxygen species and reactive nitrogen species. The formation of such species is normally highly controlled for specific signaling mechanisms (nitric oxide), respiration (superoxide), or defense (hydrogen peroxide). When cells are damaged, radicals can freely form and travel to uninjured, healthy cells. Environmental factors may also contribute to the formation of oxidative stress.

Figure 2

Progression of primary injury and secondary injury. After primary injury, the biochemical cascade that follows is secondary injury. The secondary injury can cause damage to tissue that was previously unharmed, perpetuating a cycle of oxidative stress and injury. Abbreviation: ROS, reactive oxygen species.

Figure 3

Acrolein is a reactive oxygen species implicated in secondary injury after spinal cord injury. The pi-bond reacts with proteins and lipids, altering the function of proteins or causing lipid peroxidation. The carbonyl of acrolein is still free for other reactions, such as those used for scavenging.

Figure 4

Example of the calpain-calpastatin molecular mechanisms in a damaged cell. Calcium influx causes mass activation of calpain, which cleaves protein substrates and regulators of its inhibitor, calpastatin. An efficient delivery of calpastatin or other calpain inhibitors may hinder the damage caused by the extensive activation of calpain after injury. Calpain may also serve as a protein target for nanomedical systems. Cell is not drawn to scale. For a review of explored calpain inhibitors, see Donkor.

Figure 5

Glutathione. The thiol (-SH) group contributes to its antioxidative properties. The body naturally controls the production and reduction of glutathione from its oxidized state. In cases of severe oxidative stress, the reduction occurs too slowly for cells to overcome the assault of reactive oxygen species or reactive nitrogen species.

Figure 6

Hydralazine (left) and the imine product of acrolein and hydralazine (right). After the reaction with acrolein, the Schiff base on the right is the product of hydralazine scavenging acrolein. If acrolein has already reacted with proteins, hydralazine can still react with acrolein for removal.

Figure 7

Formation of silica network with tetramethyl orthosilicate precursor. Tetramethyl orthosilicate undergoes hydrolysis in the presence of an acidic or basic catalyst followed by condensation with another silica molecule. The formation and size of silica nanoparticles is dependent on controlling the rate of both steps.