Recombinant human thioredoxin-1 promotes neurogenesis and facilitates cognitive recovery following cerebral ischemia in mice

What research is your doctor going to do based on this? Nothing is a fireable offense.
http://www.sciencedirect.com/science/article/pii/S0028390813005030

• Li Tian^{a, 1},
• Huang Nie^{a, 1},
• Yang Zhang^{b, 1},
• Yu Chen^a,
• Zhengwu Peng^c,
• Min Cai^a,
• Haidong Wei^a,
• Pei Qin^a,
• Hailong Dong^{a, ,} ,
• Lize Xiong^{a, , ,}

• ^a Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, 127th Changle West Road, Xi'an 710032, China
• ^b Department of Orthopedic Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China
• ^c Department of Psychosomatic Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China

  Open Access

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Highlights

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rhTrx-1 ameliorated spatial learning and memory deficits induced by ischemia.

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rhTrx-1 promoted ischemia-induced neurogenesis in DG.

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rhTrx-1 enhanced proliferation and neuronal differentiation of cultured NSCs.

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Neurogenesis enhanced by rhTrx-1 was inhibited by U0126 – inhibitor of ERK signaling pathway.

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Abstract

Cerebral ischemia (CI) can induce loss of hippocampal neurons, causing cognitive dysfunction such as learning and memory deficits. In adult mammals, the hippocampal dentate gyrus contains neural stem cells (NSCs) that continuously generate newborn neurons and integrate into the pre-existing networks throughout life, which may ameliorate cognitive dysfunction following CI. Recent studies have demonstrated that recombinant human thioredoxin-1 (rhTrx-1) could promote proliferation of human adipose tissue-derived mesenchymal stem cells and angiogenesis. To investigate whether rhTrx-1 also regulates hippocampal neurogenesis following CI and its underlying mechanisms, adult mice were subjected to bilateral common carotid arteries occlusion (BCCAO) to induce CI and treated with rhTrx-1 before reperfusion. Mice treated with rhTrx-1 showed shortened escape latencies in Morris water maze by 30 days and improvements in spatial memory demonstrated by probe trial test. Enhanced NSCs proliferation was observed at day 14, indicated by BrdU and Ki67 immunostaining. Doublecortin (DCX)⁺ cells were also significantly increased following rhTrx-1 treatment. Despite increases in BrdU⁺/NeuN⁺ cells by day 30, the double-labeling to total BrdU⁺ ratio was not affected by rhTrx-1 treatment. The promotive effects of rhTrx-1 on NSCs proliferation and differentiation were further confirmed in in vitro assays. Western blot revealed increased ERK1/2 phosphorylation after rhTrx-1 treatment, and the ERK inhibitor U0126 abrogated the effects of rhTrx-1 on NSCs proliferation. These results provide initial evidence that rhTrx-1 effects neurogenesis through the ERK signaling pathway and are beneficial for improving spatial learning and memory in adult mice following global CI.

The Expression of FOXJ1 in Neurogenesis after Transient Focal Cerebral Ischemia

Your researcher should be able to match this up with all the other neurogenesis factors and translate that into a stroke protocol.

The Expression of FOXJ1 in Neurogenesis after Transient Focal Cerebral Ischemia

Authors

Yabo Huang¹, Zheng Xu¹, Jie Cao¹, Haibo Cao¹, Shiming Zhang¹

¹Department of Neurosurgery, First Affiliated Hospital of Soochow University, Suzhou, China

Abstract

Objective and Background: FOXJ1 is a member of the Forkhead/winged-helix (Fox) family of transcription factors, which is required for the differentiation of the cells acting as adult neural stem cells which participate in neurogenesis and give rise to neurons, astrocytes, oligodendrocytes. The expression pattern of FOXJ1 in the brain after cerebral ischemia has so far not been described. In the current study, we investigated the expression pattern of FOXJ1 in the rat brain after cerebral ischemia by animal model. Methods: We performed a middle cerebral artery occlusion (MCAO) model in adult rats and investigated the expression of FOXJ1 in the brain by Western blotting and immunochemistry; double immunofluorescence staining was used to analyze FOXJ1's co-expression with Ki67. Results: Western blot analysis showed that the expression of FOXJ1 was lower than normal and sham-operated brain after cerebral ischemia, but the level of FOXJ1 gradually increased from Day 1 to Day 14. Immuohistochemical staining suggested that the immunostaining of FOXJ1 deposited strongly in the ipsilateral and contralateral hemisphere in the cortical penumbra (CP). There was no FOXJ1 expression in the ischemic core (IC). The positive cells in the cortical penumbra might migrat to the ischemic core. In addition, double immunofluorescence staining revealed that FOXJ1 was co-expressed with mAP-2 and gFAP, and Ki67 had the colocalization with NeuN, GFAP, and FOXJ1. Conclusions: All our findings suggest that FOXJ1 plays an important role on neuronal production and neurogenesis in the adult brain after cerebral ischemia.

Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4

With a lot of help from your doctor a stroke protocol can be created from this, or at least clinical trials.
http://www.fasebj.org/content/early/2012/11/26/fj.12-204800.abstract

Abstract

Mast cells (MCs) are found abundantly in the brain and the meninges and play a complex role in neuroinflammatory diseases, such as stroke and multiple sclerosis. Here, we show that MC-deficient Kit^W/Kit^W-v mice display increased neurodegeneration in the lesion area after brain trauma. Furthermore, MC-deficient mice display significantly more brain inflammation, namely an increased presence of macrophages/microglia, as well as dramatically increased T-cell infiltration at days 4 and 14 after injury, combined with increased astrogliosis at day 14 following injury. The number of proliferating Ki67⁺ macrophages/microglia and astrocytes around the lesion area is more than doubled in these MC-deficient mice. In parallel, MC-deficient Kit^W-sh/W-sh mice display increased presence of macrophages/microglia at day 4, and persistent astrogliosis at day 4 and 14 after brain trauma. Further analysis of mice deficient in one of the most relevant MC proteases, i.e., mouse mast cell protease 4 (mMCP-4), revealed that astrogliosis and T-cell infiltration are significantly increased in mMCP-4-knockout mice. Finally, treatment with an inhibitor of mMCP-4 significantly increased macrophage/microglia numbers and astrogliosis. These data suggest that MCs exert protective functions after trauma, at least in part via mMCP-4, by suppressing exacerbated inflammation via their proteases.—Hendrix, S., Kramer, P., Pehl, D., Warnke, K., Boato, F., Nelissen, S., Lemmens, E., Pejler, G., Metz, M., Siebenhaar, F., Maurer, M. Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4.