Protection Against Brain Aging

Your brain is under assault from environmental toxins, oxidant stress, inflammation, blood flow fluctuations, and excess glucose.^1,2 Collectively, these factors contribute to a state of neurotoxicity that accelerates brain aging resulting in neurodegenerative decline, Parkinson’s, and Alzheimer’s.^1-4

Currently there are no medical options to halt this steady march toward mental darkness. Pharmaceutical intervention is largely palliative and cannot cure or restore lost brain function.

For thousands of years, Chinese doctors have used gastrodin, extracted from the root of the exotic orchid, Gastrodia elata, to treat a range of cognitive problems ranging from vertigo and headaches to paralysis and seizures.^5-8

What scientists today are discovering is that gastrodin acts as a broad-spectrum “brain shield” that protects against various factors that cause age-related degradation of our mental processes.

The wide ranging brain benefits of gastrodin were long ago identified.

What has researchers excited are new findings showing that gastrodin has regenerative properties that include rebalancing neurotransmitters, improving blood flow, decreasing memory loss, protecting brain functions during a stroke, and potentially reducing risk of Alzheimer’s and Parkinsons.^9-13 In short, gastrodin provides unparalleled, multi-factorial brain protection in both extreme and everyday conditions.

Impressive human studies using gastrodin in hospital settings confirm its benefit in shielding the brain against neurological insults, including protecting the brain against memory loss that can occur when one undergoes open heart surgery!¹⁴ In the discussion that follows, we highlight leading research showing how gastrodin protects against factors that conspire to deteriorate our brain.

Neuroregeneration – Once Thought to be Impossible

Not so long ago, most scientists thought that adult brain tissue had no hope of regenerating itself. The loss of brain cells and brain function was considered irreversible. According to neurologists, once your brain had finished growing, the ongoing loss of brain cells was just a natural part of aging.¹⁵

But molecular science is revealing startling discoveries about the brain’s ability to heal itself. What scientists have now found is that the brain can regenerate the neurons involved in brain remodeling (plasticity). Plasticity is the process by which brain cells reorganize and restructure their connections to form new memories and facilitate learning.¹⁶

Scientists in China and Singapore have made remarkable findings about how a natural orchid extract called gastrodin stimulates these neuro-regenerative processes. Extracts from the Gastrodia orchid have been shown to have a beneficial influence on up to nearly 20% of the genes that control the brain’s plasticity and regrowth. In the studies, gastrodin was shown to mobilize and activate specific aspects of the brain’s regenerative activities.^9,10

Instead of succumbing to progressive brain shrinkage with constriction of one’s thoughts, feelings, and memories, brain cells have built-in natural, self-healing systems. Gastrodin can turn on and activate these regenerative mechanisms. This may turn out to be one of the most powerful methods ever discovered for preventing loss of brain function at any age.

Brain Blood Flow

 

A major cause of brain aging and many of the problems that go along with it is a reduction in blood flow to the brain. The result is that the brain becomes starved for oxygen and fuel, producing a low-grade “suffocation.”¹⁷ This reduction in brain blood flow is progressive over the course of an individual’s lifespan.¹⁸ Reduced blood flow has been proven to be a direct cause of poor cognition and memory.¹⁷ Gastrodin has repeatedly shown that it beneficially increases brain blood flow both in laboratory animals and human patients.^12,19,20

In rats with experimentally-induced massive strokes, a gastrodin-based traditional preparation greatly improved blood flow when given 30 minutes after the stroke. Even at a relatively low dose, brain blood flow was restored to normal with the gastrodin-based formula.¹⁹

Human studies are just as dramatic. In a study involving 202 patients, a gastrodin-based formula improved brain blood flow in 96% of the patients following stroke and other brain injuries.¹² In another study of patients with impaired circulation to the rear portions of their brains (where balance, vision, and coordination are processed), 95% of patients given gastrodin plus betahistine (a prescription medication) showed improved blood flow, while only 70% of betahistine control patients showing improvement.²⁰

Brain blood flow is also reduced by elevated blood sugar.²¹ The result is often memory impairment and an increased risk for Alzheimer’s disease. Gastrodin, in a recent lab study, improved insulin sensitivity, ridding the blood of excess glucose and reducing body fat.²²

What You Need to Know

The Neuroregenerative and Neuroprotective Power of Gastrodin

• Gastrodin can unlock your brain’s own self-healing, regenerative powers.
• Gastrodin fights the main mechanisms of brain aging that are common to simple age-related memory loss, to gradual-onset disorders like Alzheimer’s disease, and even to rapid-onset conditions like strokes, head trauma, and open-heart surgery “pumphead syndrome.”
• Laboratory studies reveal how gastrodin re-balances disordered brain chemicals that produce too much cellular excitation and too little of the opposing calming, inhibitory effects you need to keep your brain functioning normally.
• The combination of gastrodin’s neuro-regenerative and neuro-protective properties are opening new vistas in prevention of everything from “where-did-I-put-my-keys” memory deficits, to major neurodegenerative disorders, to destructive strokes.
• Even such apparently unrelated conditions like seizures, tics, migraines, and diabetic neuropathy are yielding to gastrodin’s healing powers.

Improved GABA Levels

While “burnout” is a popular phrase to illustrate extreme fatigue, it is a very real condition that occurs in your brain from too much stimulation . Given the multi-tasking pace of our lives, combined with the incessant information overload, most of us are suffering from an imbalance of our neurotransmitters.

Your brain is constantly working to maintain a balance between the cells that create electrical activity, and those that reduce or calm brain activity.

Brain cells modulate different neurotransmitters to excite or calm the brain. When the brain is resting or calm, it uses a neurotransmitter called GABA.²³

Heightened brain stimulation, with its increased cellular activity, puts an enormous strain on brain tissue, whereas inhibition tends to promote rest, regeneration, and healing.

This delicate balance of neurotransmitters is of tremendous importance to healthy brain function. Too much excitatory input, or too little inhibitory input, disturbs the balance, overstresses the brain, and leads to a “burn out” of brain cells.

Scientists commonly find an extreme neurotransmitter imbalance in people with Alzheimer’s and Parkinson’s diseases, in seizures, in stroke and head trauma victims, in diabetics (especially those with painful diabetic neuropathy), in people undergoing surgical anesthesia, and even in “normal” aging.^24-28

Gastrodin helps restore the vital balance of neurotransmitters. Studies show that gastrodin increases levels of the inhibitory neurotransmitter GABA by as much as 34%, which exerts a calming effect on the brain and counteracts the overactive brain activity.^11,29,30

Pharmaceutical companies are spending huge sums on research and development of drugs to control neurotransmitter imbalance. However, their approach has been not to create balance but to simply suppress excitation. Their only drug offering, Namenda^® (memantine), has had little impact on neurodegenerative diseases, and no effect on the heightened brain activity seen following low blood-flow conditions such as surgery and anesthesia.^31-33

Memory Loss

One of the greatest fears of getting older is the threat of memory loss. Not recognizing your loved ones or even remembering your name is a devastating condition. Studies show that gastrodin can help counteract many of the key processes that lead to memory loss.

When rats are subjected to toxic drugs that impair memory, they become confused and take longer to find their way through familiar mazes, or to rescue themselves from danger. The stress of dangerous situations also freezes up memory, just as it does in humans.

Gastrodin reverses those impairments, helping the bewildered animals consolidate and retrieve memories they’d already stored away.³⁴ In rats exposed to aluminum, which is thought to be a risk factor for Alzheimer’s disease, similar improvements in memory preservation were obtained even without a reduction in brain aluminum levels.³⁵

Reducing the Cognitive Risks of Open Heart Surgery

Perhaps the most dramatic demonstration of gastrodin’s ability to prevent brain aging caused by circulatory deficit comes from a recent human study done under the extreme stress of open heart surgery. During this operation, the patients’ hearts are stopped while they are kept alive only by use of the heart-lung machine. In this procedure, blood flow to the brain is reduced as fat globules introduced by the surgical trauma causes cerebral capillary beds to occlude. Up to 55% of patients may suffer memory loss and cognitive impairments after bypass surgery that can last for weeks, months, or forever following surgery.^36,37 Surgeons refer to these cognitive deficits resulting from open heart surgery as “pumphead syndrome.”³⁷

The symptoms involved in pumphead syndrome resemble accelerated brain aging, complete with circulatory deficit, inflammatory changes, and increases in abnormal proteins such as those seen in neurodegenerative diseases.³⁸ The only difference is that, instead of slowly occurring over many years, these cognitive changes occur within the single hour of open heart surgery.^38,39

In a human clinical trial, intensive care specialists in China injected gastrodin or a saline control solution in 200 patients undergoing open-heart surgery.

Prior to surgery, all of the patients tested normal on memory and cognition. After the operation they found that 42% of patients had cognitive decline, which included substantial memory loss.¹⁴

The outcome in the gastrodin treated group of patients was very different. Only 9% had any change at all from baseline. Even three months after surgery, 31% of the patients who did not receive gastrodin continued to have memory difficulties. Yet only 6% of the gastrodin group had residual memory problems.¹⁴

This study showed that even under the extreme conditions of open heart surgery gastrodin prevented rapid brain aging produced by intensive brain stress, including catastrophic loss of memory. This is the most compelling evidence yet of the clinical impact of gastrodin’s multiple brain-protecting and brain-healing effects.

Neurodegenerative Diseases

The World Health Organization estimates that neurological disease affects over a billion people worldwide and the trend is expected to continue. The WHO report states that, “The neurological burden is expected to become an even more serious and unmanageable threat to public health.”⁴⁰

Yet despite this global escalating increase in neuro-degenerative diseases, mainstream medicine is not providing much help in treating or solving this condition. Even the drugs that are currently on the market treat only symptoms rather than curing the cause of these disorders.⁴¹ Unlike prescription medication, gastrodin has strong evidence for its effectiveness in shielding the brain from destruction during the long slide into cognitive decline and dementia.

In laboratory experiments that simulate Alzheimer’s and Parkinson’s disease, gastrodin protects the cells in the brain centers that are most vital for learning and memory.^6,42-44 These are the areas that quickly degenerate under the threat of Alzheimer’s disease. With gastrodin, the result is a beneficial increase in cell survival and a decrease in cell death.

Also helpful in fighting the onset of Alzheimer’s, gastrodin switches on the enzymes that break down and clear away toxic Abeta proteins, which kill brain cells and steal memories in Alzheimer’s disease. Gastrodin’s housecleaning ability to eliminate toxic Abeta proteins may be one of the great prevention advances regarding Alzheimer’s disease.⁸

Gastrodin has been shown to reduce general brain inflammation, a major contributor to neurodegeneration.⁴⁵ Animals supplemented with gastrodin have improved learning and memory compared with their peers receiving no therapy.⁸ In the laboratory, gastrodin was proven to shift brain biochemistry away from producing the toxic Abeta proteins associated with Alzheimers, and towards a healthier, normal protein.⁸

Brain Regeneration

One of the most important genes influenced by gastrodin is the gene that produces neuronal cell adhesion molecules.⁹ These molecules are essential to the process by which brain cells find their way to link up with others as synapses. One result of this activity is that new memories can form rather than be erased or forgotten.⁶³ Gastrodin also increases the activator protein-1, a regulator of new protein formation which results in new neuron growth and improved memory.⁶⁴

In addition, gastrodin switches on the “misfolded protein response,” a self-healing mechanism that recognizes and destroys the abnormal proteins involved in brain cell death in Alzheimer’s, Parkinson’s, and Huntington’s diseases.^65,66

Stroke

Just as in patients being hooked up to the heart-lung machine during surgery, strokes involve rapid and catastrophic disruption of brain blood flow, an excess of excitatory brain activity, activation of destructive enzymes, and accumulation of inflammatory cytokines.⁴⁶ Stroke-inflicted brain damage happens in an extremely short period of time and can provide important insights into brain aging.

Gastrodin’s unique ability to balance excitatory-to-inhibitory neurotransmitter levels makes it therapeutically valuable in strokes. Rats treated with gastrodin after an experimentally-induced stroke had an increase of the inhibitory neurotransmitter GABA by up to 34% as well as increases in the protective amino acid taurine by up to 14%.^11,47

As a result, the animals given gastrodin had significantly smaller areas of brain damage and swelling; they also performed better on tests of memory and behavioral performance, compared with animals that had strokes but were not supplemented.^48-50

Similarly, when brain cells in culture were exposed to low oxygen levels (similar to a stroke), they exhibited sharp rises in excitatory neurotransmitters. Pre-treatment with gastrodin prevented that rise, and the subsequent microscopic evidence of neurotoxicity.⁵¹

Gastrodin’s ability to promote neuroregeneration is especially important when a stroke happens. Once metabolized in the body, gastrodin boosts production of an enzyme that restores normal structure to brain proteins damaged during stroke.¹³ Experimental-induced strokes in animals given gastrodin were up to 55% smaller than in untreated animals.¹³ And pretreatment with gastrodin reduced the rate of cell death by apoptosis following stroke.⁵²

Human studies have been performed in China using gastrodin in treatment of strokes, with great success. Given as an intravenous drug, gastrodin was effective in treating 97% of subjects with ischemic stroke (insufficient blood flow), compared with 74% who received conventional injections.⁵³ And, in hemorrhagic stroke (bleeding into the brain), gastrodin improved absorption of blood and swelling in 89% of treated subjects, compared with 72% who received conventional medications.⁵⁴

Seizures

Gastrodin has long been used in traditional Chinese medicine to prevent and treat seizures with impressive results. As a result, Western medicine is now seeking to exploit it as a source of antiepileptic drugs.^55,56 Following brain injury or stroke, seizures are unfortunately a common and distressing occurrence. They are the clearest example of what happens when the brain’s excitatory neurotransmitters outweigh the inhibitory ones. Rapid and uncontrolled electrical activity are hallmarks of seizure activity typically spreading to both sides of the brain in the absence of adequate inhibitory action.

In a rat model of epilepsy, treatment with gastrodin significantly reduced the frequency and time to onset of seizures; at the same time it reduced brain markers of lipid peroxidation, a side effect of prolonged seizure activity that indicates destruction of brain cell membranes.⁵⁶

Mainstream medicine treats acute seizures with GABA-like drugs that increase inhibitory brain activity (drugs such as lorazepam (Ativan^®), for example). Gastrodin naturally raises calming GABA levels in brain cells by decreasing levels of GABA-breakdown enzymes. Gastrodin supplementation also lowered seizure-prone animals’ seizure severity scores.³⁰

Anxiety

 

According to the National Institutes of Health, over 40 million adults in America suffer from anxiety disorder.⁵⁷ Like seizures, anxiety is a direct result of an imbalance between excitatory and inhibitory brain cell activity, with excitatory stimuli being predominate. Drugs used to treat anxiety, therefore, are usually ones that mimic the calming, inhibitory effects of GABA, such as the benzodiazepines (Valium, oxazepam, and others.)

Gastrodin’s two major breakdown compounds, found in brain cells after ingestion of gastrodin, have been shown to have powerful anti-anxiety effects in mice.⁵⁸ Unlike their drug counterparts, however, these gastrodin metabolites did not produce unwanted side effects such as sedation or muscle relaxant effects.

In a study involving 100 patients with neurotic anxiety, 100% of the patients showed improvement with gastrodin therapy.⁵⁹ However, in the patient group treated with conventional medicine, 78% of the patients showed improvement. Beyond just improvement, 88% of those treated with gastrodin were clinically cured of anxiety while those taking conventional medicine showed a 32% cure rate.⁵⁹

Migraine Headaches

The Gastrodia orchid from which we get gastrodin has been used for thousands of years in preventing and treating headaches in traditional Chinese medicine.⁶⁰ Now, in a laboratory model of the biochemical effects of migraine headaches, gastrodin has been compared to two approved anti-migraine drugs, sumatriptan and flunarizine.⁶⁰ Gastrodin, in a fashion similar to that of the prescription drugs, significantly reduced the expression and actions of proteins known to be involved in the pain response that occurs in migraine and other “vascular” headaches.⁶⁰

Diabetic Neuropathy

Even outside of the brain, gastrodin shows strong evidence of its “nerve shielding” effects. This is evident in studies of gastrodin and painful diabetic neuropathy, a condition in which peripheral nerves become damaged by chronic exposure to high blood glucose levels. We’ve seen that gastrodin reduces insulin resistance and speeds clearance of glucose from blood, which can help prevent neuropathy.²²

But gastrodin also seems to heal nerve fibers even after diabetic neuropathy develops. Diabetic rats exhibiting pain resulting from normally non-painful stimuli, such as light touch (allodynia) and excessive sensitivity to minor painful stimuli (hyperalgesia) showed improvement in their symptoms following gastrodin administration.⁶¹ In-depth studies revealed a decrease in the nerve cells’ excitability, precisely what we’d expect from the gastrodin compound capable of balancing out the excitatory-to-inhibitory signaling ratio in nerve cells.⁶¹ Human studies show an improvement in nerve conduction velocity and total curative rate in diabetics receiving gastrodin by injection as a drug, compared with a control group.⁶²

Summary

Every second, your brain is targeted by an onslaught of destructive events that cause it to age. Even so-called normal aging results in multiple damaging cascades of events that lead to memory loss, slowed learning reflexes, and can set one up for Alzheimer’s and Parkinson’s diseases.

Those who suffer a stroke, head injury, or undergo heart surgery can accumulate years’ worth of brain aging in a few short minutes.

In recent years, scientists have made significant advances in the understanding of the mechanisms of neuro-degeneration. They’ve even discovered silent brain-healing systems that lie latent, awaiting activation.

Gastrodin, derived from a traditional Chinese medicinal orchid, can activate dormant self-healing programs hidden in the depths of your brain.

Studies show that gastrodin fights brain aging at multiple levels, re-balancing neurotransmitters towards a calmer less overly active state, restoring brain blood flow to more youthful levels, and preventing memory loss and other cognitive changes.

The combination of these protective and self-healing effects may help slow “natural” brain aging while reducing risk for slow-onset disorders like Alzheimer’s disease. And, by similar mechanisms, gastrodin seems to slow or reverse damage done by acute events like strokes.

Gastrodin’s re-balancing act also offers promise to those suffering from seizures, migraine headaches, and even painful diabetic neuropathy.

Guarding one’s brain against daily wear and against potential catastrophes may now be possible with daily use of gastrodin.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

References

1. Available at: http://www.ninds.nih.gov/disorders/neurotoxicity/neurotoxicity.htm. Accessed July 22, 2013.
2. Adeghate E, Donáth T, Adem A. Alzheimer disease and diabetes mellitus: Do they have anything in common? Curr Alzheimer Res. 2013 Apr 29. [Epub ahead of print]
3. Sherer TB, Betarbet R, Greenamyre JT. Environment, mitochondria, and Parkinson’s disease. Neuroscientist. 2002 Jun;8(3):192-7.
4. Andersen JK. Oxidative stress in neurodegeneration: cause or consequence? Nat Med. 2004 Jul;10 Suppl:S18-25.
5. Kim BW, Koppula S, Kim JW, et al. Modulation of LPS-stimulated neuroinflammation in BV-2 microglia by Gastrodia elata: 4-hydroxybenzyl alcohol is the bioactive candidate. J Ethnopharmacol. 2012 Jan 31;139(2):549-57.
6. Kim IS, Choi DK, Jung HJ. Neuroprotective effects of vanillyl alcohol in Gastrodia elata Blume through suppression of oxidative stress and anti-apoptotic activity in toxin-induced dopaminergic MN9D cells. Molecules. 2011;16(7):5349-61.
7. Kumar H, Kim IS, More SV, Kim BW, Bahk YY, Choi DK. Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson’s disease model. Evid Based Complement Alternat Med. 2013;2013:514095.
8. Mishra M, Huang J, Lee YY, et al. Gastrodia elata modulates amyloid precursor protein cleavage and cognitive functions in mice. Biosci Trends. 2011;5(3):129-38.
9. Ramachandran U, Manavalan A, Sundaramurthi H, et al. Tianma modulates proteins with various neuro-regenerative modalities in differentiated human neuronal SH-SY5Y cells. Neurochem Int. 2012 Jun;60(8):827-36.
10. Manavalan A, Ramachandran U, Sundaramurthi H, et al. Gastrodia elata Blume (tianma) mobilizes neuro-protective capacities. Int J Biochem Mol Biol. 2012;3(2):219-41.
11. Zhang CY, Du GY, Wang W, et al. Effects of tianma gouteng fang on transmitter amino acids in the hippocampus extracellular liquids in freely moving rats subjected to brain ischemia. Zhongguo Zhong Yao Za Zhi. 2004 Nov;29(11):1061-5.
12. Lu SL, Liu X, Wang JL, et al. The development of nao li shen and its clinical application. J Pharm Pharmacol. 1997 Nov;49(11):1162-4.
13. Descamps E, Petrault-Laprais M, Maurois P, et al. Experimental stroke protection induced by 4-hydroxybenzyl alcohol is cancelled by bacitracin. Neurosci Res. 2009 Jun;64(2):137-42.
14. Zhang Z, Ma P, Xu Y, et al. Preventive effect of gastrodin on cognitive decline after cardiac surgery with cardiopulmonary bypass: a double-blind, randomized controlled study. J Huazhong Univ Sci Technolog Med Sci. 2011 Feb;31(1):120-7.
15. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science. 1997 Oct 17;278(5337):412-9.
16. Available at: http://kc.vanderbilt.edu/site/topics/98/brain-development-and-plasticity.aspx. Accessed July 23, 2013.
17. Zhang X, Li G, Guo L, et al. Age-related alteration in cerebral blood flow and energy failure is correlated with cognitive impairment in the senescence-accelerated prone mouse strain 8 (SAMP8). Neurol Sci. 2013 Apr 7.
18. Melamed E, Lavy S, Bentin S, Cooper G, Rinot Y. Reduction in regional cerebral blood flow during normal aging in man. Stroke. 1980 Jan-Feb;11(1):31-5.
19. Jingyi W, Yasuhiro M, Naoya H, et al. Observation on the effects of Chinese medicine zhenxuanyin for improving cerebral blood flow in rats with cerebral ischemia. J Tradit Chin Med. 1997 Dec;17(4):299-303.
20. Wei J-j, Zhou Y-l. Treatment of posterior circulation ischemia with gastrodin and betahistine. Practical Clinical Medicine. 2012;13(4).
21. Thambisetty M, Beason-Held LL, An Y, et al. Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging. Neurobiol Aging. 2013 Apr 19.
22. Park S, Kim da S, Kang S. Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur J Nutr. 2011 Mar;50(2):107-18.
23. Lehmann K, Steinecke A, Bolz J. GABA through the ages: regulation of cortical function and plasticity by inhibitory interneurons. Neural Plast. 2012;2012:892784.
24. Baumgartner WA, Walinsky PL, Salazar JD, et al. Assessing the impact of cerebral injury after cardiac surgery: will determining the mechanism reduce this injury? Ann Thorac Surg. 1999 Jun;67(6):1871-3; discussion 1891-4.
25. Rissman RA, Mobley WC. Implications for treatment: GABAA receptors in aging, Down syndrome and Alzheimer’s disease. J Neurochem. 2011 May;117(4):613-22.
26. Palomero-Gallagher N, Schleicher A, Bidmon HJ, et al. Multireceptor analysis in human neocortex reveals complex alterations of receptor ligand binding in focal epilepsies. Epilepsia. 2012 Nov;53(11):1987-97.
27. Petrou M, Pop-Busui R, Foerster BR, et al. Altered excitation-inhibition balance in the brain of patients with diabetic neuropathy. Acad Radiol. 2012 May;19(5):607-12.
28. Bories C, Husson Z, Guitton MJ, De Koninck Y. Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging. J Neurosci. 2013 Jan 23;33(4): 1344-56.
29. Kim HJ, Hwang IK, Won MH. Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia. Brain Res. 2007 Nov 21;1181:130-41.
30. An SJ, Park SK, Hwang IK, et al. Gastrodin decreases immunoreactivities of gamma-aminobutyric acid shunt enzymes in the hippocampus of seizure-sensitive gerbils. J Neurosci Res. 2003 Feb 15;71(4):534-43.
31. Lipton SA. Pathologically-activated therapeutics for neuroprotection: mechanism of NMDA receptor block by memantine and S-nitrosylation. Curr Drug Targets. 2007 May;8(5):621-32.
32. Schneider LS, Dagerman KS, Higgins JP, McShane R. Lack of evidence for the efficacy of memantine in mild Alzheimer disease. Arch Neurol. 2011 Aug;68(8):991-8.
33. Rimpilainen J, Pokela M, Kiviluoma K, et al. The N-methyl-D-aspartate antagonist memantine has no neuroprotective effect during hypothermic circulatory arrest: a study in the chronic porcine model. J Thorac Cardiovasc Surg. 2001 May;121(5):957-68; discussion 68-70.
34. Hsieh MT, Wu CR, Chen CF. Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats. J Ethnopharmacol. 1997 Mar;56(1):45-54.
35. Shuchang H, Qiao N, Piye N, et al. Protective effects of gastrodia elata on aluminium-chloride-induced learning impairments and alterations of amino acid neurotransmitter release in adult rats. Restor Neurol Neurosci. 2008;26(6):467-73.
36. Liu YH, Wang DX, Li LH, et al. The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery. Anesth Analg. 2009 Oct;109(4):1013-22.
37. Available at: http://www.nytimes.com/2000/09/19/science/saving-the-heart-can-sometimes-mean-losing-the-memory.html?pagewanted=all&src=pm. Accessed July 26, 2013.
38. Reinsfelt B, Westerlind A, Blennow K, Zetterberg H, Ricksten SE. Open-heart surgery increases cerebrospinal fluid levels of Alzheimer-associated amyloid beta. Acta Anaesthesiol Scand. 2013 Jan;57(1):82-8.
39. Selnes OA, McKhann GM. Neurocognitive complications after coronary artery bypass surgery. Ann Neurol. 2005 May;57(5):615-21.
40. Available at: http://www.who.int/mental_health/neurology/chapter_4_neuro_disorders_public_h_challenges.pdf. Accessed July 22, 2013.
41. Available at: http://www.alz.org/research/science/alzheimers_disease_treatments.asp. Accessed July 26, 2013.
42. Zhao X, Zou Y, Xu H, et al. Gastrodin protect primary cultured rat hippocampal neurons against amyloid-beta peptide-induced neurotoxicity via ERK1/2-Nrf2 pathway. Brain Res. 2012 Oct 30;1482:13-21.
43. Liu ZH, Hu HT, Feng GF, Zhao ZY, Mao NY. Protective effects of gastrodin on the cellular model of Alzheimer’s disease induced by Abeta25-35. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul;36(4):537-40.
44. An H, Kim IS, Koppula S, et al. Protective effects of Gastrodia elata Blume on MPP+-induced cytotoxicity in human dopaminergic SH-SY5Y cells. J Ethnopharmacol. 2010 Jul 20;130(2):290-8.
45. Dai JN, Zong Y, Zhong LM, et al. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS One. 2011;6(7):e21891.
46. Available at: http://www.uic.edu/com/ferne/pdf/pathophys0501.pdf. Accessed July 26, 2013.
47. Zeng X, Zhang Y, Zhang S, Zheng X. A microdialysis study of effects of gastrodin on neurochemical changes in the ischemic/reperfused rat cerebral hippocampus. Biol Pharm Bull. 2007 Apr;30(4):801-4.
48. Zeng X, Zhang S, Zhang L, Zhang K, Zheng X. A study of the neuroprotective effect of the phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med. 2006 Dec;72(15):1359-65.
49. Bie X, Chen Y, Han J, Dai H, Wan H, Zhao T. Effects of gastrodin on amino acids after cerebral ischemia-reperfusion injury in rat striatum. Asia Pac J Clin Nutr. 2007;16 Suppl 1:305-8.
50. Kam KY, Yu SJ, Jeong N, et al. p-Hydroxybenzyl alcohol prevents brain injury and behavioral impairment by activating Nrf2, PDI, and neurotrophic factor genes in a rat model of brain ischemia. Mol Cells. 2011 Mar;31(3):209-15.
51. Xu X, Lu Y, Bie X. Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med. 2007 Jun;73(7):650-4.
52. Yu SS, Zhao J, Zheng WP, Zhao Y. Neuroprotective effect of 4-hydroxybenzyl alcohol against transient focal cerebral ischemia via anti-apoptosis in rats. Brain Res. 2010 Jan 13;1308:167-75.
53. Li H, Fan P, Li K, Jiang J, PeI R. Effect of Naloxone combined with Gastrodin in treatment of acute cerebral infarction. China Modern Doctor. 2012:122-25.
54. He F, Xiao H, Zhang F. Clinical observation of gastrodin in the treatment of cerebral hemorrhage. Chin J Clinical Rational Drug Use. 2012;5(7B):12-13.
55. Ojemann LM, Nelson WL, Shin DS, Rowe AO, Buchanan RA. Tian ma, an ancient Chinese herb, offers new options for the treatment of epilepsy and other conditions. Epilepsy Behav. 2006 Mar;8(2):376-83.
56. Hsieh CL, Chiang SY, Cheng KS, et al. Anticonvulsive and free radical scavenging activities of Gastrodia elata Bl. in kainic acid-treated rats. Am J Chin Med. 2001;29(2):331-41.
57. Available at: http://www.nimh.nih.gov/health/publications/the-numbers-count-mental-disorders-in-america/index.shtml. Accessed July 22, 2013.
58. Jung JW, Yoon BH, Oh HR, et al. Anxiolytic-like effects of Gastrodia elata and its phenolic constituents in mice. Biol Pharm Bull. 2006 Feb;29(2):261-5.
59. Zhang YM, Zhong XM. Clinical effect of gastrodin as adjuvant treatment on anxiety neurosis. China Prac Med. 2010 Aug;5(23):160-1.
60. Luo GG, Fan WJ, Yuan XY, et al. The pharmacological mechanism of gastrodin on calcitonin gene-related peptide of cultured rat trigeminal ganglion. Yao Xue Xue Bao. 2011 Dec;46(12):1451-6.
61. Sun W, Miao B, Wang XC, et al. Gastrodin inhibits allodynia and hyperalgesia in painful diabetic neuropathy rats by decreasing excitability of nociceptive primary sensory neurons. PLoS One. 2012;7(6):e39647.
62. Yuan J, Xufeng E. Clinical observation on patients with diabetic neuropathy treated with combination of kudiazi injection and tianmasu injection. 2012.
63. Skaper SD. Neuronal growth-promoting and inhibitory cues in neuroprotection and neuroregeneration. Methods Mol Biol. 2012;846:13-22.
64. Hsieh CL, Lin JJ, Chiang SY, et al. Gastrodia elata modulated activator protein 1 via c-Jun N-terminal kinase signaling pathway in kainic acid-induced epilepsy in rats. J Ethnopharmacol. 2007 Jan 19;109(2):241-7.
65. Manavalan A, Feng L, Sze SK, Hu JM, Heese K. New insights into the brain protein metabolism of Gastrodia elata-treated rats by quantitative proteomics. J Proteomics. 2012 Apr 18;75(8):2468-79.
66. Du X, Mao R, Liu Y, Li Y, Shan Y. Gastrodine represses expression of IL-1 beta, IL-6 induced by hyperglycemia in gitter cells. Zhongguo Zhong Yao Za Zhi. 2009 Jun;34(12):1535-9.
67. Linkis P, Jørgensen LG, Dynamic exercise enhances regional cerebral artery mean flow velocity. J Appl Physiol. 1995 Jan;78(1):12-6.
68. Querido JS, Sheel AW. Regulation of cerebral blood flow during exercise. Sports Med. 2007;37(9):765-82.
69. Lista I, Sorrentino G. Biological mechanisms of physical activity in preventing cognitive decline. Cell Mol Neurobiol. 2010 May;30(4):493-503.
70. Van der Borght K, Kóbor-Nyakas DE, Klauke K, et al. Physical exercise leads to rapid adaptations in hippocampal vasculature: temporal dynamics and relationship to cell proliferation and neurogenesis. Hippocampus. 2009 Oct;19(10):928-36.
71. Pereira AC, Huddleston DE, Brickman AM, et al. An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA. 2007 Mar 27;104(13):5638-43.
72. Ploughman M. Exercise is brain food: the effects of physical activity on cognitive function. Dev Neurorehabil. 2008 Jul;11(3):236-40.
73. Floel A, Ruscheweyh R, Kruger K, et al. Physical activity and memory functions: Are neurotrophins and cerebral gray matter volume the missing link? Neuroimage. 2010 Feb 1;49(3):2756-63.
74. Ainslie PN, Cotter JD, George KP, et al. Elevation in cerebral blood flow velocity with aerobic fitness throughout healthy human ageing. J Physiol . 2008 Aug 15;586(16):4005-10.
75. Deslandes A, Moraes H, Ferreira C, et al. Exercise and mental health: many reasons to move. Neuropsychobiology. 2009;59(4):191-8.
76. Crawford JG. Alzheimer’s disease risk factors as related to cerebral blood flow. Med Hypotheses. 1996 Apr;46(4):367-77.
77. Baker LD, Frank LL, Foster-Schubert K, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010 Jan;67(1):71-9.
78. Geda YE, Roberts RO, Knopman DS, et al. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol. 2010 Jan;67(1):80-6.
79. de la Fuente-Fernandez R. Impact of neuroprotection on incidence of Alzheimer’s disease. PLoS ONE. 2006;20(1):e52.
80. Spector A, Thorgrimsen L, Woods B, et al. Efficacy of an evidence-based cognitive stimulation therapy programme for people with dementia: randomised controlled trial. Br J Psych. 2003;183(3):248-54.
81. Belleville S, Gilbert B, Fontaine F, Gagnon L, Menard E, Gauthier S. Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: evidence from a cognitive intervention program. Dement Geriatr Cogn Disord. 2006;22(5-6):486-99.
82. Available at:http://www.psychologytoday.com/blog/fulfillment-any-age/201004/building-better-brain-strengthening-your-mental-muscle. Accessed October 17, 2013.
83. Cassavaugh N, Kramer AF. Transfer of computer-based cognitive training to simulated driving in older adults. Appl Ergonomics. 2009;40(5):943-52.
84. Smith GE, Housen P, Yaffe K, et al. A cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study. J Am Geriatr Soc. 2009 Apr;57(4):594-603.
85. Mahncke HW, Connor BB, Appelman J, et al. Memory enhancement in healthy older adults using a brain plasticity-based training program: A randomized, controlled study. PNAS USA. 2006 August 15;103(33):12523-8.
86. Ball K, Berch DB, Helmers KF, et al. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002;288(18):2271-81.
87. Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of dementia in the elderly. New Engl J Med. 2003;348(25): 2508-16.