Thymulin related peptide attenuates inflammation in the brain induced by intracerebroventricular endotoxin injection

Based on significant amount of evidence, it is now generally believed, that one underlying cause for neurodegenerative diseases, could be dysregulation in inflammatory processes. The actual mechanisms involved are not yet well understood. Several studies have demonstrated the potent analgesic and anti-inflammatory actions of thymulin related peptide (PAT), in different animal pain models. In this study, we investigated the efficacy of PAT in a recently developed model of neuroinflammation, in conscious rats, caused by intracerbroventricular (ICV) injection of endotoxin (ET). Our results indicate that ICV injection of PAT alone did not elicit significant alteration of nociceptive thresholds, while ET injections produced significant thermal hyperalgesia and cold allodynia. Pretreatment with PAT resulted in significant alleviation of ET-induced hyperalgesia and increased body temperature. In other sets of experiments, ICV injection of ET resulted in a significant elevation in the concentration of pro-inflammatory mediators measured in different areas of the brain; this elevation was significantly following pretreatment with PAT. Taken together these results provide evidence in support of our hypothesis that as a potent anti-inflammatory and analgesic peptide, PAT might have potential therapeutic use for the treatment of neurodegenerative conditions induced by silent or overt inflammation.

Research highlights►Neurodegenerative diseases, could be due to discrete inflammatory processes, but the actual mechanisms involved are not yet well understood. ►Thymulin related peptide (PAT) has established analgesic and anti-inflammatory properties. We aimed to test the effects of PAT Using an animal model for neuroinflammation. ►Pretreatment with PAT resulted in significant alleviation of Endotoxin-induced hyperalgesia and increased body temperature. ►Intracerebroventricular injection of endotoxin resulted in a significant elevation in the concentration of pro-inflammatory mediators in different areas of the brain, which was significantly attenuated following pretreatment with PAT. ►PAT might have potential therapeutic use for the treatment of neurodegenerative conditions induced by silent or overt inflammation.