Response phases of traumatic CNS injury Acute cellular response

Dorn Spinal Therapy

Spine Healing Therapy

Get Instant Access

The initial damage that is a direct result of loading to the brain is defined as the primary phase of injury. Biomechanicians study this phase in order to determine tissue tolerances to mechanical loading because the effects of the mechanical insult can be more easily isolated from biochemical events occurring in the secondary or more chronic phase. Our understanding of tolerances at the cellular level is vital to developing better safety equipment and understanding mechanotransduction in the pathological range. At the time of the insult there may be a varying amount of primary damage that results from the physical force itself. This includes compromised skin, bony fractures, tissue tearing, cellular rupture, and reorientation of the tissue components. If a deformation threshold is surpassed, these structural failures result and can severely compromise brain function.

Due to the heterogeneity of CNS tissue, it is likely that loads and deformations experienced by cells in various anatomical regions are not consistent and cannot be accurately estimated by simplistic models assuming homogeneity. Certain anatomical regions may be subjected to more severe loading during impact because of differences in the material properties in that particular location (due to variations in cellular orientation, mye-lination, etc.). Anatomical regions experiencing larger strains would therefore be expected to be more susceptible to primary damage caused by the mechanical insult itself. Although identification of these regions would allow more accurate correlations between the mechanical input and patho-physiological responses, very little is currently known about local cellular strains in animal models of CNS trauma, mainly due to limitations in detection techniques.

One approach for addressing these technical limitations is the development of more sensitive methods for the detection of mechanically induced damage. Although detection of structural failures can be relatively obvious in some instances (such as the presence of large focal lesions), more subtle damage may also be present and can provide a unique opportunity for assessment of local cellular strains after trauma. Visualization of the anatomical localization of this mechanical damage can provide a more sensitive measure of the load distribution throughout the tissue. We and others have investigated nonspecific plasma membrane damage as an indicator of mechanical damage in various models of TBI and SCI (Pettus et al., 1994; LaPlaca et al., 1997; Shi and Borgens, 2000; Geddes et al., 2003; Farkas et al., 2006). This type of cellular damage occurs as a direct result of mechanical loading, creating rips or tears in the plasma membrane at regions of high local strain.

We have utilized Lucifer yellow as an indicator of acute biophysical membrane failure after TBI and SCI. Lucifer yellow is normally membraneimpermeable; therefore, cellular presence of this molecule can be used to detect plasma membrane compromise. In these experiments, Lucifer yellow was injected intrathecally 3 h prior to brain or spinal cord contusion, and animals were sacrificed 10min after injury (a schematic of the injury devices are illustrated in Fig. 3). Histological evidence demonstrated heterogeneous uptake of the permeability marker in various anatomical locations (as shown in Fig. 4), indicating that the distribution of mechanical loading in CNS tissue is complex and not well understood. Although we have focused on acute membrane damage as an indicator of the load distribution throughout the brain and spinal cord, others have explored membrane compromise as an initiator of downstream pathological events. Cell membrane damage can

A. Infinite Horizons spinal cord contusion device

B. Cortical contusion impact device

Spinal clamps

A. Infinite Horizons spinal cord contusion device

Spinal clamps

Infinite Horizon Impactor

Impactor tip

Stereotactic frame

Fig. 3. In vivo contusion injury devices. Injury devices are used to experimentally deliver prescribed injury parameters to the exposed brain or spinal cord. For example, the Infinite Horizons spinal cord contusion device (A) allows the user to select an impact force for injury, while the controlled cortical impact device (B) utilizes a pneumatic system to injure the brain at a defined tissue displacement.

Was this article helpful?

0 0

Post a comment