Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury

Abstract

Spinal cord injury (SCI) results in devastating neurological and pathological consequences, causing major dysfunction to the motor, sensory and autonomic systems. The primary traumatic injury to the spinal cord triggers a cascade of acute and chronic degenerative events, leading to further secondary injury. Many therapeutic strategies have been developed to potentially intervene in these progressive neurodegenerative events and minimize secondary damage to the spinal cord. Additionally, significant efforts have been directed towards regenerative therapies that may facilitate neuronal repair and establish connectivity across the injury site. Despite the promise that these approaches have shown in preclinical animal models of SCI, challenges with respect to successful clinical translation still remain. The factors that could have contributed to failure include important biologic and physiologic differences between the preclinical models and the human condition, study designs that do not mirror clinical reality, discrepancies in dosing and the timing of therapeutic interventions, and dose-limiting toxicity. With a better understanding of the pathobiology of events following acute SCI, developing integrated approaches aimed at preventing secondary damage and also facilitating neurodegenerative recovery is possible, and hopefully will lead to effective treatments for this devastating injury. The focus of this review is to highlight the progress that has been made in drug therapies and delivery systems, and also cell-based and tissue engineering approaches for SCI.

Inosine – a Multifunctional Treatment for Complications of Neurologic Injury

“…Current guidelines recommend that methylprednisolone is offered to patients within 8 h of acute SCI but that its use is at the discretion of the treating physician [5]. In preclinical studies, a variety of agents have shown beneficial effects in the context of traumatic SCI, many of which are anti-inflammatory and/or neuroprotective (reviewed in [9]). More recent strategies for treatment have taken advantage of advances in tissue engineering and stem cell technologies, as well as increased understanding of SCI pathobiology to encourage axonal regeneration through the native environment of the spinal cord.…”

Superoxide Dismutase‐Loaded Porous Polymersomes as Highly Efficient Antioxidants for Treating Neuropathic Pain

“…[19] Under normal healthy conditions, there are sufficient levels of SOD and other antioxidants in the spinal cord to maintain low levels of ROS. [20] However, after neural trauma, the levels of antioxidants are not sufficient to remove the excess ROS that are produced, resulting in a loss of cellular redox balance, and subsequent development of oxidative stress in the neurons and glia of the central nervous system. [21] SOD activity has also been found to decrease over time in injured neural tissue both centrally and peripherally.…”

Diagnostic Challenges inInfections related to Spinal Cord Injury

“…In patients with chronic indwelling bladder catheters (transurethral or suprapubic)., bacteremia is almost universal(culture of a randomly obtained urine sample is positive in almost 98% of cases) [7].…”

“…Much has changed since ancient Egyptian physician viewed spinal injury "an ailment not be treated" [1,].More than 250,000 Americans currently suffer from the consequence of spinal cord injury(SCI) and,with an annual incidence of 40 cases per million population, over 11,000 new cases of SCI occur in the United States each year [2,].About one third of SCI patients develop infection during hospitalization, with an overall incidence of 35 episodes of hospital acquired infection/1000 hospital days [3].SCI are most often caused by physical trauma [4].In the US, Motor Vehicle accidents are most common cause of SCIs; second are falls, then violence such as gunshot wounds, then sports injuries [5].Other causes of SCIs include, attempted suicide, military conflicts, and iatrogenic injury, caused by an improperly done medical procedures such as an injection into spinal column [6][7][8].In Malaysia motor vehicle accidents(66%) and falls(28%) are the main cause of SCIs [9].Most infections that occur in SCI patients also affect able-bodied patient, but the frequency and clinical characteristics of infections vary between those populations. Whereas urinary tract infections are the most common [10],pneumonia has the highest infection-associated mortality [11],and infections of pressure sores and underlying bone are probably most difficult to manage [12].Contributory factors to SCIinfection include, frequent insertion of urologic, vascular, orthopedic, respiratory ,gastrointestinal, and neurosurgical devices predispose to various prosthesis-related infections [3].Infection frequently manifests differently in the SCI population than in able-bodied individuals.…”