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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 Publisher Pubmed



Mokhtari T1 ; Akbari M1 ; Malek F1 ; Kashani IR1 ; Rastegar T1 ; Noorbakhsh F2 ; Ghazikhansari M3 ; Attari F4 ; Hassanzadeh G1
Authors
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Authors Affiliations
  1. 1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: DARU# Journal of Pharmaceutical Sciences Published:2017


Abstract

Background: Ischemic 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). Methods: In 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. Results: T3 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). Conclusions: The 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 abstract: The effects of intracerebroventricular microinjection of T3on memory and learning in rat model of ischemic brain stroke. © 2017 The Author(s).
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