Induction of mitochondrial biogenesis enhances neurogenesis and cognitive recovery following ischaemic stroke

 You didn't answer the question; EXACTLY HOW WILL RECOVERY BE GUARANTEED!
Bad research and your doctor and hospital will need to get human testing done.

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING?

This might help in getting it done:

Oxaloacetate Activates Brain Mitochondrial Biogenesis, Enhances the Insulin Pathway, Reduces Inflammation, and Stimulates Neurogenesis July 2014

 The latest here:

Induction of mitochondrial biogenesis enhances neurogenesis and cognitive recovery following ischaemic stroke

Fuhai Bai, 

Zonghong Long, 

Jing Yang, 

Ping Liu, 

Zhuoxi Wu, 

Hongxu Chen, 

Youliang Deng, 

Min Ying, 

Shanshan Zhang, 

Jiaxin Li, 

Yanjuan Chen, 

Huizhong Wen, 

Min Zhang, 

Ying Xiong & 

Hong Li 

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Abstract

Purpose

Stroke can cause severe cognitive impairment in patients. Recently, neurogenesis has been proposed as a potential approach to improve cognitive abilities after stroke. However, no effective treatment strategy currently exists for stimulating hippocampal neurogenesis to promote cognitive recovery. Therefore, this study investigated the mechanisms underlying the increase in hippocampal neurogenesis induced by mitochondrial biogenesis.

Methods

To achieve the objective, mice subjected to the global cerebral ischaemia (GCI) model via bilateral common carotid artery occlusion were used to investigate mitochondrial biogenesis in vivo through western blotting, transmission electron microscopy, and immunofluorescence staining. Hippocampal neurogenesis was assessed using immunofluorescence staining. Cognitive functions were evaluated using the open field test, novel object recognition, fear conditioning, and Morris water maze. In addition, an in vitro oxygen–glucose deprivation model served as a stroke analogue. Neurite outgrowth in primary neurons was quantified using immunofluorescence staining, while mitochondrial function parameters, including adenosine triphosphate, mitochondrial membrane potential, and reactive oxygen species, were measured using specific assay kits. Lentiviruses were used to manipulate mitochondrial biogenesis both in vivo and in vitro.

Results

We observed that the time course of mitochondrial biogenesis matched that of neurogenesis in the hippocampal dentate gyrus (DG) following GCI. Promoting mitochondrial biogenesis enhanced neurogenesis in the DG, lengthened neurites, and improved mitochondrial function, collectively alleviating cognitive deficits following stroke. Conversely, inhibition of mitochondrial biogenesis had the opposite effect. In addition, ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) was identified as a crucial component of mitochondrial biogenesis(How was it delivered and the amounts?). UQCRC1 knockdown impaired neurogenesis and cognitive abilities in mice.

Conclusion

This study highlights that mitochondrial biogenesis plays a pivotal role in neurogenesis within the hippocampal DG and may represent a promising strategy for treating cognitive impairment associated with ischaemic stroke.

Graphical Abstract

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Oxaloacetate Activates Brain Mitochondrial Biogenesis, Enhances the Insulin Pathway, Reduces Inflammation, and Stimulates Neurogenesis

All these good things happening to strokes in mice. Whom is going to test this out in humans? Or are survivors going to have to become their own guinea pigs because the stroke medical world is too afraid to do anything other than the failed status quo? 

Oxaloacetate Activates Brain Mitochondrial Biogenesis, Enhances the Insulin Pathway, Reduces Inflammation, and Stimulates Neurogenesis 

1. Heather M. Wilkins1,2,
2. Janna L. Harris3,
3. Steven M. Carl2,
4. E Lezi4,
5. Jianghua Lu1,
6. J. Eva Selfridge5,
7. Nairita Roy5,
8. Lewis Hutfles2,
9. Scott Koppel2,
10. Jill Morris1,2,
11. Jeffrey M. Burns1,2,5,
12. Mary L. Michaelis2,6,
13. Elias K. Michaelis2,6,
14. William M. Brooks1,2,3 and
15. Russell H. Swerdlow1,2,5,7,*

+ Author Affiliations

1. ¹Department of Neurology
2. ²University of Kansas Alzheimer's Disease Center
3. ³Hoglund Brain Imaging Center
4. ⁴Department of Rehabilitation Medicine
5. ⁵Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160 USA
6. ⁶Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045 USA
7. ⁷Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160 USA

1. ↵*Corresponding author: Russell H. Swerdlow, MD, University of Kansas School of Medicine, MS 2012, Landon Center on Aging, 3901 Rainbow Blvd, Kansas City, KS 66160, E-mail: rswerdlow@kumc.edu

• Received May 31, 2014.
• Revision received July 2, 2014.
• Accepted July 8, 2014.

Abstract

Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies, and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA), affects brain bioenergetics, insulin signaling, inflammation, and neurogenesis we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions, or post-translational modifications of mRNA and proteins (PGC1α, PRC, NRF1, TFAM, COX4I1, CREB, p38 MAPK, and AMPK) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mTOR, and P70S6K phosphorylation. OAA lowered NFκB nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal VEGF mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts, and neurite length increased in OAA-treated mice. ¹H-MRS showed OAA increased brain lactate, GABA, and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation, and activates hippocampal neurogenesis.