Characterizing the role of the neuropeptide substance P in experimental subarachnoid hemorrhage

Christine Barry, Stephen Helps, Corinna van den Heuvel, Robert Vink

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    21 Citations (Scopus)


    Background: Raised intracranial pressure (ICP) following SAH predicts poor outcome and is due to hemorrhage volume and possibly, brain edema, hydrocephalus and increased volume of circulating intracranial blood. Interventions that reduce edema may therefore reduce ICP and improve outcome. The neuropeptide substance P (SP) mediates vasogenic edema formation in animal models of ischemic stroke, intracerebral hemorrhage and brain trauma, and may contribute to development of increased ICP. SP (NK1 tachykinin receptor) blockade using n-acetyl-l-tryptophan (NAT) reduces edema and improves outcome in these models. This study therefore assessed whether SP mediates edema formation in experimental SAH. Methods: SAH was induced in rats by either injection of autologous blood into the prechiasmatic cistern (injection SAH) or by arterial puncture of the Circle of Willis (filament SAH). NAT was injected (i.v.) 30 min after SAH induction. Subgroups were assessed for brain water content, SP and albumin immunoreactivity, and functional outcome at 5, 24 and 48 h or ICP over 5 h. Results: A secondary ICP increase occurred within 2 h of SAH. Brain edema followed filament SAH (p < 0.001) and correlated with functional deficits (r = 0.8, p < 0.01). Increased albumin immunoreactivity (p < 0.001) indicated vasogenic edema. However, NAT treatment did not improve ICP, edema or outcome. Conclusions: Experimental SAH produced secondary ICP elevation, vasogenic brain edema and functional deficits, although it is unclear if edema contributed to ICP. Blockade of SP did not improve any outcome parameters, suggesting that neurogenic inflammation may be less critical than other factors in these models.

    Original languageEnglish
    Pages (from-to)143-151
    Number of pages9
    JournalBrain Research
    Publication statusPublished - 10 May 2011


    • Brain edema
    • Intracranial pressure
    • Neurological outcome
    • Subarachnoid hemorrhage
    • Substance P


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