Critical roles of decompression in functional recovery of ex vivo spinal cord white matter

Human spinal cord injury (SCI) is usually accompanied by persistent cord compression. Experimental data demonstrate that compression of the traumatized cord results in rapid neurological decline over hours. Undertaking decompression in humans within this time frame has proved impractical, with the time to surgery in studies of urgent decompression averaging between 10 and 24 h. There is, therefore, an important need for a therapy to prevent the neurological deterioration of patients prior to decompressive surgery. The aim of this study was to determine if hypothermia prevents compressive SCI, thereby limiting neurological decline. Rats were subjected to a moderate mid-thoracic SCI and spacers were inserted to compress the spinal cord by 45%. Decompression, by removal of the spacer, was performed immediately, and at 2 or 8 h post-injury. Hypothermia (33 degrees C) was commenced in half the animals at 30 mins post-injury and maintained for 7.5 h, with the other half remaining normothermic (37.3 degrees C). Motor recovery was assessed weekly, and the volume and area of tissue damage determined at the end of the 8-week study period. The results demonstrate that hypothermia significantly improves the behavioral and histological outcome of animals undergoing 8 h of compressive injury (the primary outcome measure). The hypothermia-treated group regained weight-supported locomotion (Basso-Beattie-Bresnahan [BBB] locomotor assessment score 9.5 +/- 0.9), while the normothermic group remained severely paraparetic (BBB score 5.3 +/- 0.6; p

Section: Comparison With Previous Studies Of Hypothermia In Scimentioning

confidence: 55%

Hypothermia Prior to Decompression: Buying Time for Treatment of Acute Spinal Cord Injury

Batchelor

Kerr

Gatt

et al. 2010

“…We hypothesize that a similar effect might be occurring at the compressed lesion, whereby ion channel derangement may play a factor in conduction block. Additionally, we have shown that membrane damage is only a small contributor in quasi-static compressive trauma (Ouyang et al, 2009). These clues direct us towards other mechanisms of damage, possibly related to ion channel disruptions.…”

Section: Introductionmentioning

confidence: 61%

“…Compressive deformation was performed with the multimodal soft tissue tester developed in previous studies (Ouyang et al, 2008(Ouyang et al, , 2009. A standard double sucrose gap chamber was implemented in the testing system to record the electrophysiological response of ventral white matter during mechanical loading (Shi and Borgens, 1999;Shi and Whitebone, 2006;Fig.…”

Section: Sustained Compression and Decompression Of Ventral White Matmentioning

confidence: 99%

Compression Induces Acute Demyelination and Potassium Channel Exposure in Spinal Cord

Ouyang

Sun

et al. 2010

Self Cite

Crush to the mammalian spinal cord leads to primary mechanical damage followed by a series of secondary biomolecular events. The chronic outcomes of spinal cord injuries have been well detailed in multiple previous studies. However, the initial mechanism by which constant displacement injury induces conduction block is still unclear. We therefore investigated the anatomical factors that may directly contribute to electrophysiological deficiencies in crushed cord. Ventral white matter strips from adult guinea pig spinal cord were compressed 80%, either briefly or continuously for 30 min. Immunofluorescence imaging and coherent anti-Stokes Raman spectroscopy (CARS) were used to visualize key pathological changes to ion channels and myelin. Compression caused electrophysiological deficits, including compound action potential (CAP) decline that was injury-duration-dependent. Compression further induced myelin retraction at the nodes of Ranvier. This demyelination phenomenon exposed a subclass of voltage-gated potassium channels (K(v)1.2). Application of a potassium channel blocker, 4-aminopyridine (4-AP), restored the CAP to near pre-injury levels. To further investigate the myelin detachment phenomenon, we constructed a three-dimensional finite element model (FEM) of the axon and surrounding myelin. We found that the von Mises stress was highly concentrated at the paranodal junction. Thus, the mechanism of myelin retraction may be associated with stress concentrations that cause debonding at the axoglial interface. In conclusion, our findings implicate myelin disruption and potassium channel pathophysiology as the culprits causing compression-mediated conduction block. This result highlights a potential therapeutic target for compressive spinal cord injuries.

“…For instance, studies conducted on ex vivo spinal cord samples demonstrated that 60% compression at a measured rate of 0.05 mm/sec yields only a 2% reduction in CAP amplitude (Ouyang et al, 2009). In the present study, severe blast loading produced a 60% compression at a rate of 60 m/sec with a resulting 60% reduction in conduction.…”

Section: Discussionmentioning

confidence: 97%

Novel Model to Investigate Blast Injury in the Central Nervous System

Connell

Gao

Shi

2011

Self Cite

Blast-induced neurotrauma (BINT) is a common injury modality associated with the current war efforts and increasing levels of terrorist activity. Exposure to the primary blast wave generated by explosive devices causes significant neurological deficits and is responsible for many of the war-related pathologies. Despite research efforts, the mechanism of injury is still poorly understood. To this end, we have established a novel ex vivo model for the direct observation and quantification of BINT at the tissue level. The model provides a quantifiable and reproducible method to illustrate the mechanism of BINT. Isolated sections of guinea pig spinal cord white matter were exposed to a supersonic shockwave using a blast generator with small-scaled explosives. The blast wave impact with isolated tissue was observed using focused shadowgraphy with a high-speed camera recording at 90,000 fps. Concurrently, functional deficits were measured by monitoring the production of compound action potentials using a double sucrose gap-recording chamber. Additionally, anatomical deficits were measured after blast exposure with a dye exclusion assay to visualize axonal membrane permeability. Our findings demonstrate that direct exposure to the blast wave compressed nervous tissue at a rate of 60 m/sec and led to significant functional deficits. Damage to the isolated spinal cord was marked by increased axonal permeability, suggesting rapid compression from the shockwave-generated high strain rates that resulted in membrane disruption. The model provides new insight into the mechanism of BINT and permits direct observation that may contribute to the development of appropriate treatment regimens.