Recombinant human erythropoietin improves functional recovery in patients with severe traumatic brain injury: A randomized, double blind and controlled clinical trial

You will have to hire a researcher to complete testing in stroke survivors, otherwise it will never get done. Basically blood doping like athletes do illegally. More red blood cells sounds like something useful immediately post-stroke. Don't do this on your own.
Blood doping is a method of increasing athletic performance by artificially increasing an athlete's red blood cell (RBC) count. Because red blood cells carry oxygen to the muscles, having a higher RBC count can dramatically improve an athlete's aerobic capacity and delay fatigue.
http://www.sciencedirect.com/science/article/pii/S0303846716303328

• Zhong-min Li, MD^a,
• Yi-lei Xiao, MD^a,
• Jian-xin Zhu, MD^a,
• Feng-yang Geng, MD^a,
• Chuan-jun Guo, MD^a,
• Zong-lei Chong, MD^a,
• Le-xin Wang, MD PhD FRACGP^{b, ,}

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http://dx.doi.org/10.1016/j.clineuro.2016.09.001

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Highlights

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EPO treatment following severe traumatic brain injury improves functional recovery.

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EPO treatment decreases serum neuron specific enolase and S-100β protein.

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EPO treatment is not associated with thromboembolic events or severe infections.

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Abstract

Objective

To investigate the short-term effect of recombinant human erythropoietin (EPO) on patients with severe traumatic brain injury.

Methods

One hundred and fifty-nine patients with severe traumatic brain injury were randomly divided into EPO (n = 79) and control group (n = 80). EPO group was treated with subcutaneous injection of EPO (100 units/kg) on day 1, 3, 6, 9 and 12 following the brain injury. Glasgow outcome scores (GOS) were used to evaluate the outcomes three months after the treatment. Serum neuron specific enolase (NSE) and S-100β protein were measured within the first three months after treatment.

Results

In the end, 146 patients (75 of the EPO group and 71 of the control group) completed the trial. Three months after the treatment, Good recovery was found in 33.3% of the EPO and 12.6% of the control group patients (p < 0.05). Serum NSE and S-100β protein were decreased gradually in both groups after treatment, but their levels in the EPO group were lower than that of control group (p < 0.05). There was no statistically significant difference in blood pressure, hemoglobin levels, pneumonia, sepsis or thromboembolic events between the two groups three months after the treatment (p > 0.05).

Conclusion

Treatment with five doses of recombinant human erythropoietin is associated with an improved functional recovery in patients with severe traumatic brain injury. This treatment does not seem to increase the risk of thromboembolic events or severe infections.

Cobalt speeds us up and slows us down - blood doping

I know this sounds illegal but read what this does.
http://www.rosincerate.com/2015/06/cobalt-speeds-us-up-and-slows-us-down.html
Blood doping

Cobalt salts such as cobalt chloride can apparently be used to boost athletic performance. When dissolved into our body liquids, cobalt ions activate a molecular pathway that is otherwise turned on when our tissues aren't getting enough oxygen (i.e. hypoxia). This pathway leads to increased production of the protein erythropoietin (EPO), which in turn acts to increase the number of red blood cells available to move oxygen around our bodies (erythropoiesis). So cobalt essentially tricks our body into making more red blood cells. While cobalt salts have been explored as a means of treating anemia (not having enough red blood cells), it appears that some athletes and horse trainers are using it to try and gain an advantage. The deliberate enhancement of red blood cell numbers for purposes other than healing is known as blood doping. This can facilitate things like running really fast or far by ensuring there is more oxygen to support the involved muscles. As it hasn't been well studied, it's not clear exactly how much of an impact cobalt has on athletic performance. Nevertheless, cobalt salts are cheap, easy to acquire, and don't need to be injected, so their non-medical use is expected to continue.

Sounds a hell of a lot cheaper and easier than using HBOT. What do we need to do to get a research scientist to prove this one way or the other? Would this be enough to save the damaged neurons from going down the drain? Or will this fall thru the cracks like every other research idea of stroke in the last 50 years? Proving once again that we can't wait for that great stroke association to get going. 

Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria-Fornix–Lesioned Rats

How soon is your doctor following up with this in human clinical trials?
http://nnr.sagepub.com/content/early/2015/04/04/1545968315572389.abstract?

1. William Almaguer-Melian, PhD1
2. Daymara Mercerón-Martínez, MSc2
3. Nancy Pavón-Fuentes, PhD1
4. Esteban Alberti-Amador, PhD1
5. Rilda Leon-Martinez1
6. Nuris Ledón, PhD3
7. Susana Delgado Ocaña4
8. Jorge A. Bergado Rosado, PhD1

1. ¹Centro Internacional de Restauración Neurológica, La Habana, Cuba
2. ²Centro de Neurociencias de Cuba, La Habana, Cuba
3. ³Centro de Inmunología Molecular, La Habana, Cuba
4. ⁴Universidad de La Habana, La Habana, Cuba

1. Jorge A. Bergado Rosado, Centro Internacional de Restauración Neurológica, Ave 25, No. 15805, Playa 11300, La Habana, Cuba. Email: bergado@neuro.ciren.cu

Abstract

Background. Erythropoietin (EPO) upregulates the mitogen activated protein kinase (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and is critical for normal brain development. Objective. We hypothesized that EPO could modulate the plasticity mechanisms supporting spatial memory recovery in fimbria-fornix–transected animals. Methods. Fimbria-fornix was transected in 3 groups of rats. Seven days later, EPO was injected daily for 4 consecutive days within 10 minutes after training on a water maze task. Results. Our results show that EPO injections 10 minutes after training produced a substantial spatial memory recovery in fimbria-fornix–lesioned animals. In contrast, an EPO injection shortly after fimbria-fornix lesion surgery does not promote spatial-memory recovery. Neither does daily EPO injection 5 hours after the water maze performance. EPO, on the other hand, induced the expression of plasticity-related genes like arc and bdnf, but this effect was independent of training or lesion. Conclusions. This finding supports our working hypothesis that EPO can modulate transient neuroplastic mechanisms triggered by training in lesioned animals. Consequently, we propose that EPO administration can be a useful trophic factor to promote neural restoration when given in combination with training.

Erythropoietin: Powerful protection of ischemic and post-ischemic brain

Sounds like something that should immediately be put into clinical trials. What the hell are we waiting for? Trillions of neurons will die hourly until we start stopping the neuronal cascade of death.
http://ebm.sagepub.com/content/239/11/1461.abstract?

1. Anh Q Nguyen*
2. Brandon H Cherry*
3. Gary F Scott
4. Myoung-Gwi Ryou
5. Robert T Mallet⇑

1. Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, TX 76107-2699

1. Robert T Mallet. Email: robert.mallet@unthsc.edu

1. ↵* Anh Q Nguyen and Brandon H Cherry contributed equally to the preparation of this manuscript.

Abstract

Ischemic brain injury inflicted by stroke and cardiac arrest ranks among the leading causes of death and long-term disability in the United States. The brain consumes large amounts of metabolic substrates and oxygen to sustain its energy requirements. Consequently, the brain is exquisitely sensitive to interruptions in its blood supply, and suffers irreversible damage after 10–15 min of severe ischemia. Effective treatments to protect the brain from stroke and cardiac arrest have proven elusive, due to the complexities of the injury cascades ignited by ischemia and reperfusion. Although recombinant tissue plasminogen activator and therapeutic hypothermia have proven efficacious for stroke and cardiac arrest, respectively, these treatments are constrained by narrow therapeutic windows, potentially detrimental side-effects and the limited availability of hypothermia equipment. Mounting evidence demonstrates the cytokine hormone erythropoietin (EPO) to be a powerful neuroprotective agent and a potential adjuvant to established therapies. Classically, EPO originating primarily in the kidneys promotes erythrocyte production by suppressing apoptosis of proerythroid progenitors in bone marrow. However, the brain is capable of producing EPO, and EPO’s membrane receptors and signaling components also are expressed in neurons and astrocytes. EPO activates signaling cascades that increase the brain’s resistance to ischemia-reperfusion stress by stabilizing mitochondrial membranes, limiting formation of reactive oxygen and nitrogen intermediates, and suppressing pro-inflammatory cytokine production and neutrophil infiltration. Collectively, these mechanisms preserve functional brain tissue and, thus, improve neurocognitive recovery from brain ischemia. This article reviews the mechanisms mediating EPO-induced brain protection, critiques the clinical utility of exogenous EPO to preserve brain threatened by ischemic stroke and cardiac arrest, and discusses the prospects for induction of EPO production within the brain by the intermediary metabolite, pyruvate.

Erythropoietin: still on the neuroprotection road

I wish they would stop using neuroprotection, its too bland and gives no sense of urgency, the neuronal cascade of death has a ring to it.
http://tan.sagepub.com/content/5/3/161.abstract?etoc

Abstract

Acute stroke is one of the major causes of death and disabilities. Since the 1980s many clinical studies have been conducted to evaluate neuroprotective approaches to treat this important brain vascular event. However, to date the only drug approved (recombinant tissue plasminogen activator [rtPA]) represents a thrombolytic, nonneuroprotective approach. An important neuroprotective strategy is based on erythropoietin (EPO). Exogenously administered EPO exhibits neuroprotective effects in numerous animal models, through the activation of anti-apoptotic, anti-oxidant and anti-inflammatory pathways as well as through the stimulation of angiogenic and neurogenic events. The capability of EPO to cross the blood–brain barrier after systemic administration and its effective therapeutic window are advantages for human acute stroke therapy. However, a multicenter stroke trial where recombinant human EPO (rhEPO) was combined with rtPA had negative outcomes. The present paper reviews the EPO neuroprotective strategy and its mechanisms in ischemic stroke and in other human nervous system diseases.

Erythropoietin enhances cell proliferation and survival of human fetal neuronal progenitors in normoxia

normoxia - normal atmospheric pressure at sea level, ie. not HBOT.
But hard to read and understand.
http://www.sciencedirect.com/science/article/pii/S0006899312003496
Abstract

Extensive data reporting the neurogenerative, neuroprotective and neuroregenerative potential of erythropoietin (EPO), mainly on RNA level, can be found in the literature. However, there is still a poor knowledge on the response of neuronal progenitor cells (NPC) upon stimulation with EPO in terms of the protein species involved. Herein, the effect of EPO on the proliferation of human mesencephalic NPC (hmNPC) under normoxia is monitored using cellular assays and proteomic analysis (two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry). The administration of EPO increased the proliferation of hmNPC within 4 days after application. It positively influenced the cell-cycle progression by affecting the G2 phase of the cell cycle. A proteomic analysis of the protein expression in hmNPC cultures 4 days after EPO treatment identified 8 proteins differentially expressed in EPO-treated cultures. It is likely that one or more of the identified proteins are involved in cellular pathways that promote cell proliferation and differentiation of hmNPC under normoxia. Their further characterization could provide cellular targets for the development of new therapeutic agents to treat CNS injury. Moreover, as EPO signaling is hypoxia-inducible, our findings may also indicate the beneficial effect of EPO to mimic hypoxia, while bypassing its negative effects, to culture human fetal midbrain-derived progenitor cells.

Impact of inhibition of EPO treatment-mediated neurogenesis in the dentate gyrus of the hippocampus on restoration of spatial learning after TBI

Testing in rats, Lets start human testing and see if it helps plain strokes.
http://www.ncbi.nlm.nih.gov/pubmed/22414310

Abstract

Our previous study demonstrates that delayed (initiated 24hours post injury) erythropoietin (EPO) therapy for traumatic brain injury (TBI) significantly improves spatial learning. In this study, we investigated the impact of inhibition of EPO treatment-mediated neurogenesis on spatial learning after experimental TBI. Young male Wistar rats (318+7g) were subjected to unilateral controlled cortical impact injury. TBI rats received delayed EPO treatment (5000U/kg in saline) administered intraperitoneally once daily at 1, 2, and 3days post injury and intracerebroventricular (icv) infusion of either a mitotic inhibitor cytosine-b-D-arabinofuranoside or vehicle (saline) for 14days. Another 2 groups of TBI rats were treated intraperitoneally with saline and infused icv with either a mitotic inhibitor Ara-C or saline for 14days. Animals receiving sham operation were infused icv with either Ara-C infusion or saline. Bromodeoxyuridine (BrdU) was administered to label dividing cells. Spatial learning was assessed using a modified Morris water maze test. Animals were sacrificed at 35days after injury and brain sections stained for immunohistochemical analyses. As compared to the saline treatment, immunohistochemical analysis revealed that delayed EPO treatment significantly increased the number of BrdU-positive cells and new neurons co-stained with BrdU and NeuN (mature neuron marker) in the dentate gyrus in TBI rats. EPO treatment improved spatial learning after TBI. Ara-C infusion significantly abolished neurogenesis and spatial learning recovery after TBI and EPO treatment. Both EPO and Ara-C reduced the number of astrocytes and microglia/macrophages in the dentate gyrus after TBI. Our findings are highly suggestive for an important role of EPO-amplified dentate gyrus neurogenesis as one of the mechanisms underlying EPO therapeutic treatments after TBI, strongly indicating that strategies promoting endogenous neurogenesis may hold an important therapeutic potential for treatment of TBI.

Hypoxia sensitive genes and respiratory neuroplasticity

Not sure if I understand most of this, the complete dissertation is only 233 pages, so ask your physiatrist for it and what s/he thinks about it.
http://gradworks.umi.com/34/88/3488513.html
Abstract:
Since breathing is essential for life, the neural system controlling breathing must be robust but flexible. One strategy to maintain respiratory homeostasis is adaptive control (i.e. plasticity). One well-known form of respiratory plasticity is phrenic long-term facilitation (pLTF), a persistent enhancement of respiratory nerve output induced by acute exposure to intermittent periods of low oxygen. pLTF is BDNF synthesis-dependent and is one of several pathways that lead to phrenic motor facilitation (pMF). Over longer time periods, cellular responses to hypoxia involve transcriptional regulation of relevant proteins to aid in tissue oxygen delivery. Hypoxia inducible factor (HIF) is a transcription factor responsible for the upregulation of proteins such as vascular endothelial growth factor (VEGF) and erythropoietin (EPO). VEGF was originally known for angiogenesis and EPO was originally described as a hematopoietic factor. However, we now know that both proteins are expressed in the central nervous system where they exert neurotrophic and neuroprotective effects. Since VEGF and EPO signal via cellular cascades similar to BDNF, we wondered if spinal VEGF and EPO receptor activation are also capable of eliciting long-lasting pMF. Thus, we tested the hypotheses that VEGF, EPO, and their receptors are: 1) expressed in the phrenic motor nucleus, the ventral spinal region responsible for motor output to the major inspiratory muscle: the diaphragm, and 2) that VEGF and EPO elicit respiratory motor plasticity in a manner similar to BDNF. We demonstrate that VEGF, VEGFR-2, EPO and EPOR are all located in identified phrenic motor neurons and that acute intrathecal application of these proteins to the cervical spinal cord elicits pMF via a mechanism that requires activity of extracellular-regulated kinases (ERK1/2) and protein kinase B (Akt). Although repetitive exposure to acute intermittent hypoxia (AIH) enhances VEGF receptor expression in phrenic motor neurons, we saw no evidence that VEGF or EPO elicits an enhanced pMF following repetitive AIH. This is the first report of VEGF eliciting plasticity in any motor system, and the first report of EPO eliciting spinal respiratory plasticity. By understanding these mechanisms in detail, the potential exists to "harness" this plasticity for use in patients with chronic ventilatory insufficiency.

Biker's warning! EPO hits blood vessels to raise blood pressure in the brain

Be careful out there, although I doubt any of us are trying to become world-class athletes.
http://esciencenews.com/articles/2011/12/11/bikers.warning.epo.hits.blood.vessels.raise.blood.pressure.brain

Erythropoietin or EPO might be considered a "performance enhancing" substance for athletes, but new research published online in The FASEB Journal shows that these enhancements come at a high cost--increased risk of vascular problems in the brain. According to the study, short- or long-term use of EPO raises blood pressure by constricting arteries, which reduces the flow of blood to the brain. This finding also contradicts earlier evidence suggesting that EPO may be a viable early treatment for stroke victims. "The new findings of this study urge to scrutinize present indications for EPO, and so help to better delineate positive versus adversary health effects of EPO for each patient," said Peter Rasmussen, Ph.D., a researcher involved in the work from the Zurich Center for Integrative Human Physiology at the University of Zurich in Switzerland. "Future research should aim at developing an EPO-based agent for treatment that does not have a negative effect on the blood vessels of the brain."

To make this discovery, Rasmussen and colleagues evaluated the effects of acute high doses of EPO for three days and chronic low doses of EPO for 13 weeks in two groups of healthy males. Responsiveness of brain vessels during rest and during bike-riding exercise, with and without hypoxia, was examined. Blood vessels were also analyzed using ultrasound measurements and by measuring how much oxygen reached the brain. They found that prolonged EPO administration increased hematocrit, while acute administration did not. They also found that both groups had increases in blood vessel constriction and higher blood pressure.

"EPO is used by doctors to increase red blood cells in sick people who can't make enough of them: it's called honest medicine. When EPO is used by healthy bikers and runners to boost their performance, it's called cheating. Now we know that folks who use EPO covertly are cheating not only the time-clock, but themselves," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Not only is EPO likely unsafe in healthy athletes, but there are many other ways to build up stamina without drugs."