13 May 2008
Animal models in spinal cord injury
Disappointing clinical trials spell out a need for change in spinal cord injury models. Clinical trials for numerous neuroprotective agents developed to treat acute spinal cord injury (SCI) have been disappointing, despite therapies showing previous success in animal models. Animal models are used to study the pathology of SCI and test the therapeutic success of neuroprotective agents. However, translation of findings to humans has proven unsatisfactory. A recent paper by Akhtar and colleagues has highlighted the main basis for such disappointing clinical results and the need to reassess the current animal models [1].
SCI results from blows that fracture or dislocate vertebrae, causing a tear of spinal cord tissue or trapping nerves. This subsequently affects nerve signal transduction and may result in paralysis. The most common location of SCI in patients is cervical; however, the sites of injury normally induced in experiments are dorsal and in the thoracic spine. In the laboratory setting animal stress is also a contributing factor to physiological discrepancies in results. Similarly, the use of anaesthesia influences the pathology of recovery and contributes neuroprotective effects itself.
Current methods for interpreting functional outcomes in laboratory animals tend to concentrate on a particular neuropathic component or response and are not comprehensive. Considering the consequences of human SCI are often multifaceted, secondary treatments are frequently required which influence the pharmacological environment; an aspect presently not taken into account with animal models.
The inter- and intra-species disparities in SCI pathopysiology, such as spinal anatomy, blood flow, injury healing times and pathology, present the most inherent impediments with animal models. Therefore, the fundamental requirement in this field is to develop more reliable models of improved relevance to humans.
For example, research underway at the University of Leeds, funded by the Dr Hadwen Trust, is applying diffusion tensor magnetic resonance imaging to sections of human spinal cord tissue. The data will be used to construct a physiologically and anatomically detailed computer model of spinal cord tissue. The virtual tissue model may allow development of a non-invasive clinical index of the regeneration of pathways in the spinal cord. This would have potential to replace some animal studies for assessing the effects of novel therapies. Read more here…
Reference
1. Animal Models in Spinal Cord Injury: A Review. Aysha Z Akhtar, John Pippin, Chad Sandusky. Physicians Committee for Responsible Medicine, Washington, DC. Reviews in the Neurosciences (In Press).