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. 2017 Feb 15;25(1):4.
doi: 10.1186/s40199-017-0169-x.

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  1 , Mohammad Akbari  1 , Fatemeh Malek  1 , Iraj Ragerdi Kashani  1 , Tayebeh Rastegar  1 , Farshid Noorbakhsh  2 , Mahmoud Ghazi-Khansari  3 , Fatemeh Attari  4 , Gholamreza Hassanzadeh  5
Affiliations

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 et al. Daru. .

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. The effects of intracerebroventricular microinjection of T3on memory and learning in rat model of ischemic brain stroke.

Keywords: BDNF; CA1; GDNF; Stroke; Triiodothyronine.

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Figures

Fig. 1
Fig. 1
Effects of ICV injection of T3 on percentage of Body weight change following brain ischemia in rat on day 1, 7 and 21. *p < 0.05 compared to Co and Sh groups; # p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
Fig. 2
Fig. 2
Effects of ICV injection of T3 on spatial memory and learning following brain ischemia in rat. a Mean latency to platform, b Mean Distance traveled to platform (c) time spent in the platform and (d) distance spent in the platform. * p < 0.05 compared to Co and Sh groups; #p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
Fig. 3
Fig. 3
Effects of ICV injection of T3 on STL in the passive avoidance test following brain ischemia in rat. a LT1: Latency time at 24 h before to ischemia; LT2: Latency time at 1h before to ischemia; b STL1: Step-through latency 24 h after solvent and T3 administration; STL3: Step-through latency 3 days after solvent and T3 administration, STL7: Step-through latency 7 days after solvent and T3 administration, STL21: Step-through latency 21 days after solvent and T3 administration, *p < 0.05 compared to Co and Sh groups; #p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
Fig. 4
Fig. 4
Effects of ICV injection of T3 on neurotrophic factor gene expression of hippocampal CA1 region following brain ischemia in rat. a BDNF gene expression, b GDNF gene expression. *p < 0.05 compared to Co and Sh groups; # p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
Fig. 5
Fig. 5
Effects of ICV injection of T3 on neurotrophic factor protein concentration of hippocampal CA1 rejoin following brain ischemia in rat. a BDNF and b GDNF proteins. *p < 0.05 compared to Co and Sh groups; # p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
Fig. 6
Fig. 6
Effects of ICV injection of T3 on pyramidal neurons of CA1 region of hippocampus following brain ischemia in rat. a Nissl staining (arrows: dark neurons, ×400), b H&E staining (arrows: dark neurons, ×400), c Comparing the dark neuron number in different groups. *p < 0.05 compared to Co and Sh groups; # p < 0.05 compared to tMCAo group. Co: normal group with ICV injection of solvent, Sh: sham operated group with ICV injection of solvent; tMCAo: Ischemia induction group with ICV injection of solvent, tMCAo + T3: Ischemia induction group with ICV injection of T3
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References

    1. Xiong D, Deng Y, Huang B, Yin C, Liu B, Shi J, et al. Icariin attenuates cerebral ischemia–reperfusion injury through inhibition of inflammatory response mediated by NF-κB, PPARα and PPARγ in rats. Int Immunopharmacol. 2016;30:157–162. doi: 10.1016/j.intimp.2015.11.035. - DOI - PubMed
    1. Céspedes‐Rubio A, Jurado FW, Cardona‐Gómez GP. p120 catenin/αN‐catenin are molecular targets in the neuroprotection and neuronal plasticity mediated by atorvastatin after focal cerebral ischemia. J Neurosci Res. 2010;88(16):3621–3634. doi: 10.1002/jnr.22511. - DOI - PubMed
    1. Chan A, Yan J, Csurhes P, Greer J, McCombe P. Circulating brain derived neurotrophic factor (BDNF) and frequency of BDNF positive T cells in peripheral blood in human ischemic stroke: effect on outcome. J Neuroimmunol. 2015;286:42–47. doi: 10.1016/j.jneuroim.2015.06.013. - DOI - PubMed
    1. Murray V, Norrving B, Sandercock P, Terént A, Wardlaw J, Wester P. The molecular basis of thrombolysis and its clinical application in stroke. J Intern Med. 2010;267(2):191–208. doi: 10.1111/j.1365-2796.2009.02205.x. - DOI - PubMed
    1. Black JM, Hawks JH, Keene AM. Medical-surgical nursing: Clinical management for positive outcomes. 2005.

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