Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats

Qu, Huiling; Zhao, Mei; Zhao, Shanshan; Xiao, Ting; Song, Chengguang; Cao, Yunpeng; Jolkkonen, Jukka; Zhao, Chuansheng

doi:10.1016/j.neuroscience.2014.11.040

Cited by 38 publications

(23 citation statements)

References 53 publications

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“…Immunofluorescence staining. As described previously (24), DNA was denatured and the incorporated BrdU was detected immunologically using a sheep anti-BrdU antibody (1:500; catalog no. ab1893; Abcam, Cambridge, MA, USA).…”

Section: -Bromo-2-deoxyuridine (Brdu) Labelingmentioning

confidence: 99%

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

Zhang

Wang

et al. 2016

Molecular Medicine Reports

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Brain plasticity is very sensitive to the environment. Certain neurotrophic factors and neurotransmitter receptors, including brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate response element‑binding protein (CREB), stromal cell‑derived factor‑1 (SDF‑1) and its specific receptor, C-X-C motif chemokine receptor 4 (CXCR4), are important in neurogenesis in adult animals. In the present study, the effects of environmental enrichment (EE) on neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ), and the protein expression levels of BDNF, CREB, SDF‑1 and CXCR4 were investigated. Adult rats were randomly assigned as controls or underwent EE for 30 days. Subsequently, immunofluorescence staining was used to analyze cell proliferation in the DG and SVZ, and the differentiation and survival of newly‑formed cells in the hippocampus. The protein expression levels of BDNF, phosphorylated CREB (pCREB), protein kinase A catalytic subunit α, SDF‑1 and CXCR4 in the hippocampus were assayed by western blotting. Cognitive function was assessed in a Morris water maze. EE improved cognitive function, and increased the proliferation, differentiation and survival of newly‑formed neurons in the DG of adult rats; however, EE did not activate neurogenesis in the SVZ. Furthermore, EE enhanced the protein expression levels of BDNF, pCREB, SDF-1 and CXCR4 in the hippocampus. These results provide a theoretical basis to explain the beneficial effects of EE on healthy, adult rats.

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Section: -Bromo-2-deoxyuridine (Brdu) Labelingmentioning

confidence: 99%

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

Zhang

Wang

et al. 2016

Molecular Medicine Reports

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“…The discovery of continuous adult neurogenesis in human brains provides a second therapeutic time window and gives hope to neural repair after ischemic stroke. Encouragingly, it was found that compared to quiescent state, the production of neuroblasts was significantly increased in the adult brain after ischemic stroke [21][22][23][24][25][26] . It was found that stroke gave rise to a 31-fold increase of the number of new-born neurons in the ipsilateral striatum [15] .…”

Section: Ischemic Stroke Promotes Neurogenesismentioning

confidence: 99%

Pharmacological approaches promoting stem cell-based therapy following ischemic stroke insults

Zhu

Szeto²,

Bao

et al. 2018

Acta Pharmacol Sin

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Stroke can lead to long-term neurological deficits. Adult neurogenesis, the continuous generation of newborn neurons in distinct regions of the brain throughout life, has been considered as one of the appoaches to restore the neurological function following ischemic stroke. However, ischemia-induced spontaneous neurogenesis is not suffcient, thus cell-based therapy, including infusing exogenous stem cells or stimulating endogenous stem cells to help repair of injured brain, has been studied in numerous animal experiments and some pilot clinical trials. While the effects of cell-based therapy on neurological function during recovery remains unproven in randomized controlled trials, pharmacological agents have been administrated to assist the cell-based therapy. In this review, we summarized the limitations of ischemia-induced neurogenesis and stem-cell transplantation, as well as the potential proneuroregenerative effects of drugs that may enhance efficacy of cell-based therapies. Specifically, we discussed drugs that enhance proliferation, migration, differentiation, survival and function connectivity of newborn neurons, which may restore neurobehavioral function and improve outcomes in stroke patients.

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“…[127,128] However, even though age and vascular risk factors may compromise the treatment effect, neurorestorative therapies have still improved the functional recovery after stroke in aged and diseased subjects. [97,129,130] Currently, constraint-induced movement therapy (CIMT), physical fitness training and selective serotonin reuptake inhibitors (SSRI) are the most effective, recovery-promoting treatments for stroke patients. The efficacy of CIMT has been demonstrated in several clinical trials, among others the EXCITE randomized clinical trial, which included 222 stroke patients.…”

Section: Expert Commentarymentioning

confidence: 99%

Promoting recovery from ischemic stroke

Schmidt

Minnerup

2016

Expert Review of Neurotherapeutics

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Over recent decades, experimental and clinical stroke studies have identified a number of neurorestorative treatments that stimulate neural plasticity and promote functional recovery. In contrast to the acute stroke treatments thrombolysis and endovascular thrombectomy, neurorestorative treatments are still effective when initiated days after stroke onset, which makes them applicable to virtually all stroke patients. In this article, selected physical, pharmacological and cell-based neurorestorative therapies are discussed, with special emphasis on interventions that have already been transferred from the laboratory to the clinical setting. We explain molecular and structural processes that promote neural plasticity, discuss potential limitations of neurorestorative treatments, and offer a speculative viewpoint on how neurorestorative treatments will evolve.

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Forced limb-use enhanced neurogenesis and behavioral recovery after stroke in the aged rats

Cited by 38 publications

References 53 publications

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

Pharmacological approaches promoting stem cell-based therapy following ischemic stroke insults

Promoting recovery from ischemic stroke

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