title: Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.
abstract: The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India.
authors.forename: Puja
authors.initials: P
authors.lastname: Gulati
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Muthuraman
authors.forename: Amteshwar S
authors.initials: AS
authors.lastname: Jaggi
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015220:Calcium Channels / Q000378:metabolism*; D004195:Disease Models, Animal; D005682:Gadolinium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D053580:Muscle Strength / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D045442:Rotarod Performance Test; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D005682:Gadolinium; D000110:Acetylcholinesterase; D005978:Glutathione; C038958:gadolinium chloride; D002118:Calcium