Effect of L-pGlu-(1-benzyl)-l-His-l-Pro-NH against in-vitro and in-vivo models of cerebral ischemia and associated neurological disorders.

Central nervous system plays a vital role in regulation of most of biological functions which are abnormally affected in various disorders including cerebral ischemia, Alzheimer's and Parkinson's (AD and PD) worldwide. Cerebral stroke is an extremely fatal and one of the least comprehensible neurological disorders due to limited availability of prospective clinical approaches and therapeutics. Since, some endogenous peptides like thyrotropin-releasing hormone have shown substantial neuroprotective potential, hence present study evaluates the newer thyrotropin-releasing hormone (TRH) analogue L-pGlu-(1-benzyl)-l-His-l-Pro-NH for its neuroprotective effects against oxygen glucose deprivation (OGD), glutamate and HO induced injury in pheochromocytoma cell lines (PC-12 cells) and in-vivo ischemic injury in mice. Additionally, the treatment was further analyzed with respect to models of AD and PD in mice. Cerebral ischemia was induced by clamping both bilateral common carotid arteries for ten minutes. Treatment was administered to the mice five minute after restoration of blood supply to brain. Consequential changes in neurobehavioural, biochemical and histological parameters were assessed after a week. L-pGlu-(1-benzyl)-l-His-l-Pro-NH showed significant reduction in glutamate, HO and OGD -induced cell death in concentration and time dependent manner. Moreover, L-pGlu-(1-benzyl)-l-His-l-Pro-NH resulted in a substantial reduction in CA1 (Cornus Ammonis 1) hippocampal neuronal cell death, inflammatory cytokines, TNF-α, IL-6 and oxidative stress in hippocampus. In addition, L-pGlu-(1-benzyl)-l-His-l-Pro-NH was found to be protective in two acute models of AD and PD as well these findings demonstrate the neuroprotective potential of L-pGlu-(1-benzyl)-l-His-l-Pro-NH in cerebral ischemia and other diseases, which may be mediated through reduction of excitotoxicity, oxidative stress and inflammation.