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Intranasal C3a treatment ameliorates cognitive impairment in a mouse model of neonatal hypoxic–ischemic brain injury

Research output: Contribution to journalArticle

Javier Morán, Anna Stokowska, Frederik R. Walker, Carina Mallard, Henrik Hagberg, Marcela Pekna

Original languageEnglish
JournalExperimental Neurology
Early online date4 Jan 2017
DOIs
Publication statusE-pub ahead of print - 4 Jan 2017

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Abstract

Perinatal asphyxia-induced brain injury is often associated with irreversible neurological complications such as intellectual disability and cerebral palsy but available therapies are limited. Novel neuroprotective therapies as well as approaches stimulating neural plasticity mechanism that can compensate for cell death after hypoxia–ischemia (HI) are urgently needed. We previously reported that single i.c.v. injection of complement-derived peptide C3a 1 h after HI induction prevented HI-induced cognitive impairment when mice were tested as adults. Here, we tested the effects of intranasal treatment with C3a on HI-induced cognitive deficit. Using the object recognition test, we found that intranasal C3a treated mice were protected from HI-induced impairment of memory function assessed 6 weeks after HI induction. C3a treatment ameliorated HI-induced reactive gliosis in the hippocampus, while it did not affect the extent of hippocampal tissue loss, neuronal cell density, expression of the pan-synaptic marker synapsin I or the expression of growth associated protein 43. In conclusion, our results reveal that brief pharmacological treatment with C3a using a clinically feasible non-invasive mode of administration ameliorates HI-induced cognitive impairment. Intranasal administration is a plausible route to deliver C3a into the brain of asphyxiated infants at high risk of developing hypoxic–ischemic encephalopathy.

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