CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

The aim of the present study was to investigate whether ciliary neurotrophic factor (CNTF) plays its neuroprotective role following hypoxic injury through the activation of signal transducer and activator of transcription 3 (STAT3) signaling. Firstly, to determine whether CNTF exerts its effects via STAT3 following hypoxic injury, cultured neurons from the cerebral cortex of mice were prepared and a neuronal model of hypoxia was then established. The neurons exposed to hypoxia were then pre-treated with CNTF and transfected with small interference RNA (siRNA) targeting STAT3 (STAT3 siRNA) using polybrene, or with STAT3Tyr705 mutant or STAT3Ser727 mutant using an electroporation system. The survival, proliferation and neurite outgrowth of the neurons subjected to different treatments were also determined. RT-qPCR and western blot analysis were employed to examine the expression levels of STAT3, p-STAT3Tyr705 and p-STAT3Ser727 following treatment with CNTF and other treatments. Our results revealed that treatment with CNTF: i) protected neurons from hypoxic injury by promoting survival and neurite growth; ii) induced a significant increase in the levels of STAT3, STAT3pTyr705 and the STAT3pTyr705/STAT3 ratio; it did not however, significantly affect the levels of STAT3pSer727 in the hypoxic cerebral cortex neurons. Transfection of the hypoxic neurons pre-treated with CNTF with STAT3 siRNA or STAT3Tyr705 neutralized the protective effects exerted by CNTF. The findings of our study thus demonstrate that CNTF protects neurons from hypoxic injury through the activation of STAT3pTyr705.

Cognitive improvement of mice induced by exercise prior to traumatic brain injury is associated with cytochrome c oxidase.

Though the evidence demonstrated that voluntary exercise programs could be implemented to enhance recovery of cognitive function induced by traumatic brain injury (TBI), the exact mechanisms were still not known. We proposed that the cognitive improvement induced by exercise in TBI mice is associated with cytochrome c oxidase (COX). To demonstrate this hypothesis, adult mice were housed with or without access to a running wheel (RW) for three weeks followed by TBI operation. Acquisition of spatial learning and memory retention was assessed by using the Morris Water Maze (MWM) on days 15 post TBI. The synaptic density was measured by Golji staining. Immunohistochemistry (IHC) for NeuN, GFAP and growth associated protein 43 (GAP43) were also performed. Using Western blot, the expressions of COX I, II, III, BDNF, synapsin I, synaptophysin (SYP) and GAP43 in hippocampus of TBI mice were determinated. Lastly, CcO activity and ATP amount were also detected. Results showed that voluntary exercise prior TBI: (i) counteracted the cognitive deficits and neuron and synaptic density loss associated with the injury; (ii) increased the levels of COX I, II, III, BDNF, synapsin I, SYP and GAP43; (iii) switched the mitochondrial CcO activity and ATP amounts. These studies demonstrated that the COX plays an important role in exercise's cognitive effects in TBI model and also provide evidence that RW training is a promise exercise for traumatically injured mice.

Neurotrophin expression in neural stem cells grafted acutely to transected spinal cord of adult rats linked to functional improvement.

It is well known that neural stem cells (NSC) could promote the repairment after spinal cord injury, but the underlying mechanism remains to be elucidated. This study showed that the transplantation of NSC significantly improved hindlimb locomotor functions in adult rats subjected to transection of the spinal cord. Biotin dextran amine tracing together with the stimulus experiment in motor sensory area showed that little CST regeneration existed and functional synaptic formation in the injury site. Immunocytochemistry and RT-PCR demonstrated the secretion of NGF, BDNF, and NT-3 by NSC in vitro and in vivo, respectively. However, only mRNA expression of BDNF and NT-3 but not NGF in injury segment following NSC transplantation was upregulated remarkably, while caspase-3, a crucial apoptosis gene, was downregulated simultaneously. These provided us a clue that the functional recovery was correlated with the regulation of BDNF, NT-3, and caspase-3 in spinal cord transected rats following NSC transplantation.