Improvement of memory and learning by intracerebroventricular microinjection of T3 in rat model of ischemic brain stroke mediated by upregulation of BDNF and GDNF in CA1 hippocampal region

Tahmineh Mokhtari,Farshid Noorbakhsh,Iraj Ragerdi Kashani,Gholamreza Hassanzadeh,Fatemeh Malek,Mohammad Akbari,Mahmoud Ghazi-Khansari,Fatemeh Attari,Tayebeh Rastegar

doi:10.1186/s40199-017-0169-x

Abstract

BackgroundIschemic stroke is a common leading cause of death and disability with lack of effective therapies. In this study, T3 was intra-ventricularly injected to evaluate gene expression and protein concentration of and brain-derived neurotrophic factor (BDNF) and Glial cell-derived neurotrophic factor (GDNF) in hippocampal CA1 region in rat model of brain ischemia/reperfusion (I/R).MethodsIn this study, transient middle cerebral artery occlusion (tMCAo) was used as model of ischemic brain stroke. Rats were randomly divided in four groups of Co, Sh, tMCAo and tMCAo + T3. Then, a single dose of intra-ventricular T3 was administered via a Hamilton syringe. Passive avoidance test was used as behavioral investigations. After 21 days, the animals were sacrificed and their brains were used for molecular and histopathological studies.ResultsT3 significantly improved the learning and memory compared with tMCAo group according to Morris water maze findings (P < 0.05). Step-through latency (STL) significantly decreased in tMCAo group (P < 0.05). There were significant increase in the STL of T3 group compared with tMCAo group (P < 0.05).A significant reduction in BDNF mRNAs and protein levels were observed in the tMCAo compared with Co and Sh group (P < 0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in tMCAo + T3 group compared with Co, Sh and tMCAO groups (P < 0.05).ConclusionsThe results of current study demonstrated that T3 had therapeutic effects on cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF) in CA1 region of hippocampus.Graphical abstractThe effects of intracerebroventricular microinjection of T3on memory and learning in rat model of ischemic brain stroke.

Highlights

Ischemic stroke is a common leading cause of death and disability with lack of effective therapies
Transient middle cerebral artery occlusion Focal cerebral ischemia was induced using in the left hemisphere transient middle cerebral artery occlusion (tMCAo) method
An intraluminal 4–0 nylon monofilament (Doccol Control group (Co)., USA) was used to occlude the medial carotid artery (MCA). This filament was inserted into the common carotid artery (CCA) and conducted into internal carotid artery (ICA) to block the origin of the MCA

Summary

Introduction

Ischemic stroke is a common leading cause of death and disability with lack of effective therapies. A complex series of biochemical and molecular mechanisms including excitotoxic glutamatergic signaling, outburst of reactive oxygen species (ROSs), over-production of inflammatory mediators induce the pathogenesis of cerebral ischemia by sudden death of a portion of neurons which leading wide range of neurological defects [3,4,5]. It was shown that among brain neurons, pyramidal neurons of hippocampal CA1 region are sensitive to ischemia condition [6]. These neurons play critical roles in learning and memory functions. Passive avoidance memory impairment following brain ischemia is associated with degeneration of pyramidal neurons [7]

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