Context Metformin induced AMP-activated protein kinase (AMPK) and protected neurons in cerebral ischaemia. Objective This study examined pretreatment with metformin and activation of AMPK in molecular and behavioral levels associated with memory. Materials and methods Rats were pretreated with metformin (200 mg/kg) for 2 weeks and 4-vessels occlusion global cerebral ischaemia was induced. Three days after ischaemia, memory improvement was done by passive avoidance task and neurological scores were evaluated. The amount of Brain-Derived Neurotropic Factor (BDNF) and phosphorylated and total P70S6 kinase (P70S6K) were measured. Results Pretreatment with metformin (met) in the met + ischaemia/reperfusion (I/R) group reduced latency time for enter to dark chamber compared with the sham group (p50.001) and increased latency time compared with the I/R group (p50.001). Injection of Compound C (CC) (as an AMPK inhibitor) concomitant with metformin reduced latency time in I/R rats compared with the I/R + met group (p50.05). Neurological scores were reduced in met treated rats compared with the sham group. Pretreatment with metformin in I/R animals reduced levels of pro-BDNF compared with the I/R group (p50.001) but increased that compared with the sham group (p50.001). The level of pro-BDNF decreased in the met + CC + I/R group compared with the met + I/R group (p50.01). Pretreatment with metformin in I/R animals significantly increased P70S6K compared with the I/R group (p50.001). Conclusion Short-term memory in ischaemic rats treated with metformin increased step-through latency; sensory-motor evaluation was applied and a group of ischaemia rats that were pretreated with metformin showed high levels of BDNF, P70S6K that seemed to be due to increasing AMPK. ARTICLE HISTORY

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For stem cell therapy of degenerative diseases, it is necessary to differentiate stem cells into the specific lineage. There are several growth factors which have been used for differentiation of stem cells. Some growth factors can dose-dependently induce differentiation of stem cells so that the increase of growth factor concentration results in production of the higher level of differentiated cells. However, due to the toxicity of some differentiation factors (e.g. retinoic acid), the lower dose of growth factors for the specific lineage differentiation of stem cells is desirable. This paper suggests a new approach in the field of controlled growth factor delivery system using semiconductor nanocrystals; known as quantum dots (QDs). This system contains polymeric microencapsulated growth factor which is conjugated to near infrared (NIR) absorbing QDs. The control release of growth factors from microcapsules in the culture plates can be achieved by irradiation. To modulate growth factor release in response to stem cells needs for differentiation, the intensity and period of irradiation will be controlled. Our hypothesis is based on the fact that QDs can absorb NIR energy and by excitation of electrons and then vibrational relaxation of them become heated when they were irradiated and then release growth factors. We believe that controlled growth factors delivery through the suggested system is an effective method to reduce the amount of growth factors required for differentiation of stem cells.