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

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.

Comparison between the effect of human Wharton’s jelly–derived mesenchymal stem cells and levetiracetam on brain infarcts in rats

“…23 Our results showed that MCAO caused an increase in the infarct size as compared with the sham group, the histopathological examination revealed edema, increase in the cellular permeability as well as infiltration of inflammatory cells. Global ischemia is produced by transient bilateral carotid artery stenosis, while focal ischemia is produced by transient MCAO.…”

Prognostic value of thyroid hormones in acute ischemic stroke – a meta analysis

“…Several fundamental studies previously explored the possible mechanisms underlying the prognostic role of thyroid hormones in AIS. Some experiments found that exogenous T3 and T4 elevated the concentrations of certain important neuroprotective agents, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in a rat model of brain ischemia/reperfusion 32 – 35 . Two studies reported evident reductions of tissue infarction and edema in a transient middle cerebral artery occlusion (t-MCAO) model of male mice injected with T3, and attributed this anti-edema effect to suppression of the expression of aquaporin-4 (AQP4) water channels by T3 36 , 37 .…”

Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment

“…- Sabbaghziarani et al 2017: similar to previous study from Mokhtari et al (2017), here cerebral ischemia was induced by MCAo in male Wistar rats; a group of rats was also injected with T3 (25 μg/kg, IV injection) at 24 hours after ischemia. BDNF gene and protein levels (along with nestin and Sox2) were increased upon T3 treatment vs ischemic group.…”

“…- Mokhtari et al 2017: in this in vivo study rats underwent transient middle cerebral artery occlusion (tMCAo) to induce ischemic brain stroke. Rats were randomly divided in four groups: Co (control), Sh (sham), tMCAo and tMCAo + T3 (intracerebroventricular injection of T3 at 25 ug/kg body administered 24 after reperfusion).…”