Research Projects

Stroke is one of the leading causes of death and long-term disability worldwide. The major type of stroke i.e. ischemic stroke is caused by cerebral thrombosis or embolism within a blood vessel. Currently, FDA approved tissue plasminogen activator (t-PA) mediated thrombolytic treatment is the only available treatment for stroke patients. Neuroprotection by the drug treatment to control the stroke induced secondary damage remains a major challenging issue and not a single compound is approved by FDA to do so. One of the early major events of stroke pathophysiology is oxidative stress. While ROS play crucial roles in human physiological processes, its overproduction is an important mediator of ischemic stroke induced brain damage. Brain is especially vulnerable to ROS due to low levels of endogenous antioxidant enzymes such as glutathione peroxidase and catalase. Main sources of ROS in cerebral ischemia are mitochondria, NADPH oxidase, phospholipase A2, and cyclooxygenase. ROS can directly promote inflammation by increasing blood brain barrier (BBB) permeability through upregulation of vascular endothelial growth factor (VEGF), and by inducing the expression of cytokines, matrix remodeling enzymes, including metalloproteases, and proinflammatory genes through NF-kβ activation. Hence, controlling the oxidative stress by antioxidant is remained a major focus of the neuroprotection following stroke onset. A very upcoming strategy as therapeutics for cerebral ischemic stroke is cell penetrating peptides (CPP). Several preclinical studies on number of peptides with different sizes such as NA-1, TAT-STEP etc showed very promising result. However, not a single one is clinically approved for stroke patients. In this context the target of the current proposal is to screen a number of short peptides mainly tri-peptides for their neuroprotective property in OGD (oxygen glucose deprivation), an in vitro model of stroke. Originally, these peptides were designed on the basis of a hypothesis that presence of an aromatic ring in their structures will provide an antioxidant property to them since there are several naturally occurring antioxidants which contain aromatic moiety in their structure (e.g. resveratrol, pieced, curcumin, tocopherol and many others).