Abstract:
Spinal cord injury has been shown to induce an ongoing chronic inflammatory state, beginning as soon as a few weeks post injury and sometimes persisting for years. This state of ongoing inflammation creates an inhibitory milieu around the injury site resulting in the inhibition of axonal repair/regeneration and the onset of neuropathic pain in patients.
Connexin 43 hemichannels have been shown to be a major component in perpetuating this inflammatory state. Tonabersat is a validated hemichannel modulating drug which we have used to block these
Connexin 43 hemichannels in an effort to reduce the chronic inflammatory environment.
To date there are no therapies available which successfully limit this state of chronic inflammation. In order to investigate whether Tonabersat reduces chronic inflammation, we utilised a chronic contusion spinal cord injury rat model. Following initial contusion, the animals were given a 6 week period for the chronic inflammation to manifest, after which
Tonabersat was administered orally for a 4 week period.
The effect of Tonabersat on astrogliosis and microgliosis was examined. The treated animals showed a reduction in the level of astrocyte staining compared to nontreated animals. Additionally we saw a reduced presence of microglia around the lesion between treated and non-treated animals. These data indicate that connexin hemichannel modulation may be able to alleviate chronic spinal cord inflammation and potentially improve long-term outcomes.
