The role of substance p in ischaemic brain injury

Abstract

Stroke is a leading cause of death, disability and dementia worldwide. Despite extensive pre-clinical investigation, few therapeutic treatment options are available to patients, meaning that death, severe disability and the requirement for long-term rehabilitation are common outcomes. Cell loss and tissue injury following stroke occurs through a number of diverse secondary injury pathways, whose delayed nature provides an opportunity for pharmacological intervention. Amongst these secondary injury factors, increased blood-brain barrier permeability and cerebral oedema are well-documented complications of cerebral ischaemia, whose severity has been shown to be associated with final outcome. Whilst the mechanisms of increased blood-brain barrier permeability and cerebral oedema are largely unknown, recent evidence suggests that the neuropeptide substance P (SP) plays a central role. The aim of this review is to examine the role of SP in ischaemic stroke and report on the potential utility of NK1 tachykinin receptor antagonists as therapeutic agents.

Figure 1

Secondary injury pathways that occur following ischaemic stroke.

Figure 2

Increased SP immunreactivity was observed at 24h following acute ischaemic stroke (A), as compared to shams (B). This was particularly prominent in the perivascular tissue.

Figure 3

Marked BBB permeability, as measured by Evan’s Blue (EB) extravasation (A) and cerebral oedema, as measured by the wet weight-dry weight method (B) were observed at 24h following stroke. This was ameliorated by treatment with an NK1 tachykinin receptor antagonist. *** p < 0.001 compared to vehicle; ⁺ p < 0.05 compared to sham.