Abstract
In this randomized blinded study, we investigated caffeine 5 mg/kg treatment given directly after neonatal brain hypoxia ischemia. Brain morphology, behavior and key brain infiltrating immune populations were examined. Caffeine treatment significantly improves outcome when compared to phosphate buffered saline. Flow cytometric analysis of immune responses revealed no persistent immunological alterations. Given its safety caffeine emerges as a candidate for neuroprotective intervention after neonatal brain injury.
Highlights
Neuroprotective strategies are needed for neonatal hypoxia ischemia brain injury (HI)
A single dose caffeine 5 mg/kg administered directly after neonatal HI significantly decreased atrophy by 44% (p
Local and systemic immune populations investigated 24h, 72h and two weeks after HI, revealed surprisingly few alterations considering the decrease in atrophy and improved outcome (Fig 2)
Summary
Neuroprotective strategies are needed for neonatal hypoxia ischemia brain injury (HI). Mild hypothermia is currently the only available treatment in widespread clinical use [1], though difficult to achieve in low income countries. When caffeine was given to treat apneas cerebral palsy significantly diminished [2], suggesting that caffeine might be a candidate for the treatment of brain HI. Much is published concerning the risk of adverse effects of caffeine use. Dosage is of major importance since caffeine is a competitive inhibitor of adenosine A1, A2A and A2B receptors at lower doses whereas higher concentrations inhibit phosphodiesterase, responsible for many of the adverse effects reported [3]. Available prospective randomized studies of perinatal use have been unable to show adverse effects of clinically relevant doses of caffeine [3]
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