Research Projects

Sepsis is a dysregulated inflammatory response to infection, leading to multiple organ failure. Sepsis-induced cerebral damage is the most common type, seen in 70% of sepsis patients in ICU. Neuropeptides, including bombesin-like peptides like gastrin-releasing peptide (GRP) and neuromedin B, have been implicated in the pathophysiology of sepsis and brain-related disorders. These peptides have been found to affect spatial learning and memory. This study will use the cecal ligation and puncture (CLP) method to induce sepsis-induced cerebral injury. Under anesthesia, a laparotomy will be performed, exposing the cecum, followed by ligation with a sterile 3-0 silk suture. The cecum will then be punctured and fecal material extruded. To investigate the role of bombesin-like peptides, neuromedin B, gastrin-releasing peptide, and phyllolitorin, specific drugs/vehicles will be used one day before and six days after the CLP procedure. Behavioral assessment will be conducted on the 7th day, memory evaluation from 8-12 days, and sacrifice of mice for blood and brain collection. The extent of hippocampal damage will be assessed using Nissl staining, while the extent of cerebral injury will be measured by quantifying apoptosis markers, biomarkers for sepsis-induced brain injury, oxidative stress markers, and inflammatory biomarkers. Specific pharmacological modulators targeting these peptides will be administered to mice subjected to sepsis-induced cerebral and cognitive injury.

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