The dynamics of axolemmal disruption in guinea pig spinal cord following compression

Abstract

Membrane damage has been postulated as a critical factor in mediating axonal degeneration in brain and spinal cord trauma. Despite compelling evidence of membrane disruption as a result of physical insults in both in vivo and in vitro studies, the dynamics of such damage over the time post injury in in vivo studies has not been well documented. Using a well-characterized in vivo guinea pig spinal cord compression model and horseradish peroxidase exclusion assay, we have documented significant membrane disruption at 1 hr, 3 days, and 7 days following injury. Furthermore, the membrane damage was found to spread laterally 10 mm beyond the center of original compression site in both rostral and caudal directions. A second-degree polynomial fit of the measured data predicts a bilateral spread of approximately 20-21 mm of membrane disruption from the epicenter of injury over a period of about 20 days. Thus, this study shows that membrane damage exists days, and possibly weeks, after spinal cord trauma in live guinea pigs. This provides the evidence necessary to investigate the role of membrane damage in triggering axonal deterioration in the future. Furthermore, this study has also revealed a long therapeutical window for membrane repair and functional enhancement following traumatic injury in the central nervous system.

Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering approach to spinal cord injury

“…in addition to behavioral recovery, PEG treatment also resulted in significant reduction of injury size [53] . The fact that the delayed application of PEG (8 h post-injury) still leads to significant functional and anatomical recovery is consistent with an earlier study which showed that membrane damage continues to exist up to 7 days after spinal cord compression in vivo [28] . Thus, PEG-mediated axonal repair would be possible for an extended period of time post-injury.…”

“…Shi, in previous studies, found that significant membrane damage exists in the spinal cord axons at 1 h, 3 days, and 7 days after controlled compression injury in vivo [28] . More importantly, the location of axonal injury expands from the original 2 mm crush site to a distance of 20 mm in each direction at 7 days post-compression [28] .…”

“…More importantly, the location of axonal injury expands from the original 2 mm crush site to a distance of 20 mm in each direction at 7 days post-compression [28] .…”

Paranodal Myelin Damage after Acute Stretch in Guinea Pig Spinal Cord

“…One possible reason that 4-AP only partially restores conduction is that some of the axons that suffered myelin damage also suffered axonal membrane disruption, compromising the integrity of both structures which are indispensible in neuronal function. In support of such a notion, there is widespread membrane damage following spinal cord mechanical trauma (Shi, 2004;Simon et al, 2009), and compounds that are known to seal membrane disruption, such as polyethylene glycol, can also restore axonal conduction (Donaldson et al, 2002;Shi and Borgens, 2000).…”

“…The stretch rod was released immediately after inducing the stretch injury. For electrophysiological recording, a double sucrose gap chamber was used to monitor the real-time compound action potential (CAP) as an assessment of conduction function (Shi andBlight, 1996,1997;Shi and Borgens, 2000). For anatomical study, a 1-cm segment was cut from the epicenter of the injury site immediately after stretch and examined by imaging methods.…”