Protective effects of capsaicin on ibotenate-induced excitotoxic brain injury in newborn rats

Background: Excitotoxicity is important because it is common mechanism of perinatal brain injuries. Capsaicin is an exogenous agonist of TRPV1 receptors and has a wide range of pharmacological effects. We aimed to investigate effects of different doses of capsaicin on brain damage, mast cells and inflammatory markers in a rat model of ibotenate-induced neonatal excitotoxic brain injury. Material and Methods: P5 Wistar rat pups of both sexes were divided into 8 groups (n=7 for naive-control, n=13 for each of the other groups). Except for naive-control, intraperitoneally sham-control and ibotenate groups received PBS, ibo+DMSO group received 0.1 % DMSO, ibo+capsaicin groups received 0.2, 1 and 5 mg/kg capsaicin, ibo+MK-801 group received 1 mg/kg MK-801. Thirty minutes later, sham-control received vehicle and the other groups received 10 μg ibotenate by intracerebral route. Cortical/white matter thicknesses and white matter lesion size were measured in coronal brain sections stained with cresyl-violet. Toluidine-blue-stained brain mast cells were evaluated for number and degranulation. Activin-A, IL-1β, IL-6 and IL-10 concentrations in brain tissue homogenates were measured using ELISA. Data were analyzed with one-way ANOVA followed by post-hoc Tukey test. Results: While ibotenate caused white matter lesion, decreased cortical and white matter thicknesses, increased number and degranulation of brain mast cells, increased brain tissue activin-A, IL-1β and IL-6 concentrations (P<0.01), it did not affect IL-10 level (P>0.05). In a dose-dependent manner, capsaicin alleviated ibotenate-induced cortical and white matter damages and decreased increases in mast cell number and degranulation and brain tissue activin-A, IL-1β, and IL-6 concentrations (P<0.05). Positive control MK-801 prevented ibotenate-induced changes (P<0.01). Conclusion: Capsaicin alleviates neonatal brain damage caused by excitotoxicity and related neuroinflammation including mast cell activation and increased release of pro-inflammatory cytokines. The preventive effects of capsaicin on excitotoxicity which is common mechanism in brain injuries, and on the neuroinflammation suggest that capsaicin may be protective against many types of perinatal brain damage. Key words: Perinatal brain injury, neonate, excitotoxicity, neuroinflammation, brain mast cells, capsaicin.