Spinal Cord Injury

The workgroup covers the research topics like risk factors and damage Spinal Cord Injury Research.

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Spinal Cord Injury Research

Spinal cord injury (SCI) is a tremendous incident in everyone's life. The patients suffer from neurologic deficits such as sensory and/or motor paralysis but also disorders of the vegetative nervous system (Schwab et al., 2006). Even though some of the predominantly young patients recover and return to a mostly independent life, in most cases a lifelong handicap remains. Despite fundamental progress in basic, cellular and molecular research in the last years only little is known about pathophysiological processes following spinal cord injury in humans (Schwab et al., 2006). Given the translational character the Spinal Cord Injury group is an associated member of the "European Multicenter Study about Spinal Cord Injury (EMSCI)".


Clinical trials

  • Design and conduction of diagnostic and interventional mono-/and multicentric randomized trials in patients following spinal cord injury.

Experimental models

  • SCI-models (contusion, transection)
  • Pneumonia model (Streptococcus pneumoniae)
  • Peritonitis model

Cell and molecular biology

  • Gene expression analysis (qPCR, Western Blot)
  • FACS analysis
  • Immunohistochemistry (single and double labeling)

Topics and ongoing projects

Spinal Cord Injury (SCI): Regeneration

Impermissive mileu for axonal outgrowth is composed by stop signs located in the scar and in the CNS myelin. Schwab et al., 2006. Prog Neurobiol
Substrate for regeneration: dystrophic axons following SCI (axonal tracing, BDA).
Substrate for regeneration: dystrophic axons (dark bulbs) at the lesion site following SCI (axonal tracing, BDA). Schwab et al., 2006. Prog Neurobiol

The main cause of the severity of SCI is the failure of axonal regeneration and restricted plasticity. It is well known, that the inhibitory environment repulses the axonal outgrowth following SCI.
Identification and blockade of these inhibitors may lead to axonal regeneration and gain of neurological function (Schwab et al., 2006). In addition, we investigate pathophysiological degenerative processes in in vivo models of SCI. Given distinct post-injury tissue responses putatively leading to differing therapeutic time frames.

These findings will be compared to humans. One aspect is the secondary subacute inflammatory process. Another aim is to protect the intrinsic recovery potential of injured nerve fibers following SCI, which is jeopardized by extrinsic factors such as infections (see below). In addition, visualizing the translational character, a prospective multicenter diagnostic trial but also a randomized placebo-controlled interventional trial is conducted.

Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS)

Neurogenic immune deficiency following SCI (i) occurs early within 24h, (ii) affects cells of the adaptive and innate immune system, and (iii) is most pronounced during the first week after SCI.
Schwab et al., 2006. Prog Neurobiol, 78, 91-116

Infections, i.e. pneumonia and urinary tract infections, are a leading cause of morbidity and mortality but also may dampen the intrinsic recovery potential in patients with acute spinal cord injury. It has recently become clear that SCI might increase susceptibility to infections by central nervous system (CNS)-specific mechanisms: CNS-injury induces a disturbance of the normally well-balanced interplay between the immune system and the CNS (Meisel et al., 2005).
As a result, also SCI may lead to a secondary immunodeficiency, referred to as SCI injury-induced immunodepression syndrome (Riegger et al., 2007, 2009). Our research team investigates the qualitative and quantitative aspects of immune depression triggered by SCI, referring to functional impairment of innate and specific immune functions. Here different experimental models of SCI and pneumonia are used. This enables the detection of underlying SCI-specific "neurogenic" mechanisms of the elicited immune depression and ways of pharmacological intervention. The impact of fascilitated infections on secondary damage and intrinsic recovery potential is under investigation.
Furthermore, for the identification of novel clinical strategies we are realizing a SCI-IDS clinical trial as a bedside to bench and to bedside project in order to characterize the SCI-IDS pathoimmunology and phenotype in humans in more detail. These strategies aim to provide novel targets for future pharmacological interventions in order to prevent infections limiting the intrinsic recovery potential.

Resolution of inflammation in the lesioned CNS

Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. Resolution of inflammation is defective following SCI (Schwab et al., 2001). During intact resolution, specific omega-3 polyunsaturated fatty-acid derived mediators are generated within resolving exudates (e.g., resolvin E1, protectin D1) acting as agonists for resolution (Schwab et al., 2007). Further investigations demonstrated, that these mediators promote phagocyte removal during acute inflammation by regulating leukocyte efflux, increasing macrophage ingestion of apoptotic polymorphonuclear leukocytes (PMNs) in vitro and in vivo and are therefore potent agonists for resolution of inflamed tissues (Schwab et al., 2007).
We translate the concept of resolution "behind" the blood brain barrier and its role in SCI pathophysiology and tissue remodeling. Sustained inflammation and/or impaired resolution may enhance secondary damage and degenerative processes ("tertiary damage") following SCI.

Kinetics of COX-1+ cells following CNS-injury (lesion)
Smouldering“ parenchymal monocytosis following cerebral ischaemia

"Resolution-deficit" following acute traumatic CNS-injury

Kinetics of COX-1+ cells following CNS injury illustrating a persisting accumulation of activated microglia/macrophages at the lesion site (dark bars) for up to several month following CNS injury. Schwab et al., 2002. J Neurosurgery, 96, 892-99

„Smouldering“ parenchymal monocytosis following cerebral ischaemia (CD68+, COX-1+, CD14+) at the lesion site month after human CNS injury. Schwab et al., 2001. J Neurotrauma, 18, 881-90. Beschorner et al., 2002. J Neuroimmunol, 126, 107-115

Leukocyte traffic from zymosan-inflamed tissue towards afferent lymph nodes nd spleen, qualitative.
Leukocyte traffic from zymosan-inflamed tissue towards lymph nodes and spleen, quantitative.

Can resolution of inflammation be propagated?

Leukocyte traffic from zymosan-inflamed tissue towards afferent lymph nodes nd spleen, qualitative. Proof of principle-experiments demonstrated that, complementary to orthodox anti-inflammatory treatment aiming to limit cell influx, resolution agonists foster effective cell traffic out of the inflammatory site and migration forward afferent lyphatics. Schwab, J.M., Chiang, N., Arita, M., Serhan, C.N. (2007) Nature, 447, 869-74 

Leukocyte traffic from zymosan-inflamed tissue towards lymph nodes and spleen, quantitative. Schwab, J.M., Chiang, N., Arita, M., Serhan, C.N. (2007) Nature, 447, 869-874