I love smelling the fragrant aroma of rosemary, freshly picked from my little Montreal garden, a joy of summer spice, but what does it tell us about concussions?
Is it possible that breathing in a specific scent can actually boost brain performance?
Amazingly yes, according to Dr Mark Moss, from a recent article published in Therapeutic Advances in Psychopharmacology on February 24, 2012. Dr Moss has been studying aromas for over ten years. He studies specifically how aromas can get into the blood then, once bound find their way into the brain across the blood-brain barrier. Working with co-investigator, Lorraine Olivier they made their observations with 20 healthy volunteers who participated in their study by performing mental tasks, serial subtractions plus visual information processing. The testing cubicles were infused with the aroma scent of the 1,8-cineole, which is from the cooking herb, rosemary. Translated from Latin ros marinus, as, dew of the sea the evergreen like leaves of rosemary are used to flavor roast turkey, chicken, pork and lamb. The mint family spice originated and thrives from the dry climate typical of the Mediterranean region to flavor a wide range of different cultures favorite foods, even our own family’s favorite Christmas stuffing.
The researchers set out to correlate the serum (blood) levels of 1,8-cineole with the thinking performance tabulating the number of correct responses with corresponding reaction time for each task. Different absorption levels of the rosemary aroma were assigned for varying exposure times, in effect changing concentration exposure to the herb. According to the researchers, the tested serial subtraction tests, ‘assess continuous working memory, arithmetic processing, and central composition.’ Blood serum levels of the 1,8-cineole, samples taken after the test, correlated with the performance outcome of their subtraction test but not with the rapid visual information processing task, which is an assessment of sustained attention and central executive functioning. The researchers also evaluated the mood of the volunteers before and after their testing, remarking speculatively in their conclusion, that positive mood can influence outcome by improving the cognitive performance tested but simply arousing mood cannot, with no effect on alertness attempted with forced attention Their speculation says a lot about being passionate about what you do certainly helps, doesn’t it?
So taking their summary that, ‘compounds absorbed from rosemary aroma affect cognition and subjective state independently through different neurochemical pathways,’ their rosemary aroma research poses some intriguing questions. Specifically like comments concerning the ravages of aging or more particularly, premature aging-like decline in the brain, which involves the defined progression of Alzheimer’s disease. Comments from Dr Ilkay Orhan working at Gazi University, Ankara, Turkey points to the ability of rosemary using one of its essential oils, 1,8-Cineole to inhibit a key enzyme involved in the pathogenesis of Alzheimer’s disease. Rosemary aroma appears to temporarily mimic the preferred prescribed drugs used for the treatment of Alzheimer’s disease, with its ability to inhibit acetylcholinesterase, the targeted enzyme. Now things gets interesting, let’s follow the scent.
Illustration from Kohler’s Medicinal Plants
What other systems does rosemary aroma involve itself with? Lets first look as the scent enters the lungs, what about asthma? Another paper, Therapeutic Effects of Inhaled 1,8-Cineole on Allergic Airway Inflammation outlines how rosemary extract contains what are termed,’volatile constituents’, which suppress lung interleukin-13 (IL-13). IL-13 plays an essential role in the pathogenesis of airway hyper-responsivness in asthma. The author of these observations, Ken-ichiro Inoue from the School of Pharmacy at Kitasato University of Tokyo, Japan suggests in his speculation that inhaled 1,8-cineole, ‘can be a candidate for the treatment of allergic airway diseases including bronchial asthma.’
More rosemary aroma observations from 2003 involving both the University of Pakistan in Karachi, Pakistan and the National Academy of Sciences of the Republic of Kazakhstan in Karaganda, Kazakhstan by authors: ZK ASanova, EM Sulimenov, GA Atazhanova, AD Dembitskii, RN Pak, A Dar and SM Adekenov who studied the essential oils from levant wormwood. In 1884 it was established that the main component is 1,8-cineole. The authors tested a variety of effects of 1, 8-cineole on mice including comparable reductions to acetic acid induced convulsions with similar analgesic induced effects compared to aspirin at the same dosage for both at 100mg/kg. Mice melanoma cells and carcinoma cells from mice were inhibited by 1,8-cineole at a concentration of 1 x 10-2 (minus2) inhibited their growth by 95%.
If rosemary gets bound into blood, does it affect blood pressure? I cite from Cardiovascular Effects of 1,8-cineole in Normotensive Rats published in the Canadian Journal of Physiological Pharmacology in 2002 by S Lahlou, AF Figuereido, PJ Magalhaes and JH Leal-Cardoso, Universidade Federal de Pernambucco, Recife, PE, Brazil. These authors reported 1,8-cineole vasodilatory effects directly onto vascular smooth muscle when giving bolus intravenous injections by eliciting a dose-dependent decreases in mean aortic pressure, dropping blood pressure, creating hypotension in their rats.
But can the essential oil 1, 8-cineole, a herb extract enter the blood and cross the blood-brain barrier to reach the brain following inhalation to have central nervous system effects? Here’s the conclusion from a pilot tolerability study for dementia as reported in Pharmacology, Biochemistry and Behavior from 2003 authored by N SL Perry, C Bollen, EK Perry and C Ballard involving their universities at University of Otago, Dunedin, New Zealand, Newcastle General Hospital, Newcastle Upon Tyne, England. The authors reflecting on the majority of FDA approved drugs for treating Alzheimer’s disease, …’act by countering the cholinergic deficit associated with the cognitive dysfunction and are based on the inhibition of the enzyme acetylcholinesterase (AChE). Other targets include anti-inflammatory, antioxidative and estrogenic mechanisms, nicotinic receptors, nerve growth factors with the formation of neurofibrillary tangles and AB plaques, which are the hallmarks of the diseased brain. It is increasingly evident that preventative and symptomatic treatment of Alzheimer’s disease will become a multitarget drug strategy.’
Are you still with me? Remember I stated this gets interesting at the beginning? Here’s why, I think so. It’s no good waiting for Alzheimer’s to take its full dementia effect and then start trying to stall the sweep of the dementia disease. What about early detection for Alzheimer’s, what’s out there? In a study of patients with very mild Alzheimer’s disease as reported March 8, 2012 at http://www.medscape.com/viewarticle/759975 concerning recently completed work by lead author Dr Rawan Tarawneh along with Dr David Holzman published by Megan Brooks for research performed at Washington University School of Medicine in St-Louis, Missouri, published in Neurology March 6, 2012 entitled A New Biomarker of Cognitive Decline in Alzheimer’s. ‘ Baseline levels of visinline like protein 1 (VLIP-1) measured in cerebrospinal fluid (CSF) strongly predicted the rate of cognitive decline over roughly 3 years. Memory and other cognitive abilities declined faster in patients with the highest level of VILIP-1 . a neuro calcium-sensor protein that is a sign of neuronal injury.’ Notice the critical term cited is neuronal injury with free VILIP-1 being measurable in the blood, as the new blood biomarker. What is VILIP-1, where is it, what does it do really? But before reacting with some responses to VILIP-1….
What is a good indicator of early symptoms for tracking Alzheimer’s disease? Let’s follow the scent, again. The scent of smell is also an early indication of the impending downgrade that leads to Alzheimer’s dementia. It’s now the scent of the neurobiology of disease, how Alzheimer’s disease has a unique vulnerability within the olfactory system, which provides, ‘a quintessential translational tool for understanding the synaptic dysfunction and pathological progression of the (dementia) disease.’ Quotation is from The Journal of Neuroscience 2 November 2011, 31(44): 15962-71, Sensory Network Dysfunction, Behavioral Impairments, and Their Reversibility in an Alzheimer’s Beta-Amyloidosis Model authored by DW Wesson, AH Borkowski, GE Landreth, RA Nixon, E Levy and DA Wilson. Here is their entire abstract, I think it’s brilliant work, bravo guys and girls!
“Using the Tg2576 mouse model of B-amyldosis, we show the aberrant, hyperactive olfactory network activity begins early in life, before detectable behavioral impairments or comparable hippocampal dysfunction and at a time when amyloid-B (AB) deposition is restricted to the olfactory bulb (OB). Hyperactive odor-evoked activity in the piriform cortex (PCX) and increased OB-PCX functional connectivity emerged at a time coinciding with the olfactory behavior impairments. This hyperactivity persisted until later in life when the network converted to a hyporesponsive state. This conversion was AB-dependent, because liver-X receptor agonist treatment to promote AB degradation rescued the hyporesponsive state and olfactory behavior. These data lend evidence to a novel working model of olfactory dysfunction in AD and, complimentary to other recent works, suggest that disease-relevant network dysfunction is highly dynamic and region specific, yet with lasting effects on cognition and behavior.” WOW SO COOL!
Let’s get back now to VILIP-1. I am quoting from the on-line descriptions from SANTA CRUZ BIOTECHNOLOGY INC. The company sells diagnostic kits for research purposes only using a RNA gene detection method called Western Blotting. ‘VILIP-1 is member of the neuronal calcium-binding protein superfamily. VILIP-1 is expressed in the membrane, cytoplasm and cytoskeleton of the sympathetic and parasympathetic neurons throughout the brain, except for the caudate-putamen region.The rate of VILIP-1 decreases significantly with age. VILIP-1 associates with actin in the cytoskeleton, which may translocate VILIP-1 to the membrane. VILIP-1 binds the 3′-untranslated region of trkB double-stranded mRNA in a calcium dependent manner. VILIP-1 associates with G protein-receptor kinase 1 and inhibits its binding to the membrane. VILIP-1 is involved in membrane calcium signalling and may play a role in the sensitivity of G-protein cascades to cytostolic . Decreased amounts of VILIP-1 were found in Alzheimer’s diseased brains, suggesting it may play a role in the disease.’
So let’s see here, VILIP-1 is expressed in the cytoskeleton, associates with actin. Hmmm, this sounds like my old friend tensegrity, how cells attach into a mechanistic sensing network, what I have termed the shape sensing network in previous posts. Now a part of this interactive component from cellular scaffolding, which seems to move around reattaching itself as calcium ions charge into a neuronal cell through their channel. Then somehow this whole VILIP-1 attachment thing, detaches acting like a loose scaffold connector hook, to get picked up as a sensitive predictor by Dr Rawan Tarawneh as a biomarker. It’s appropriate to recall a reminder from my Feb 19, 2012 blog post on Fractional Anistrophy of white matter lesions in mTBI:
When ions rush in, they tend to destroy the scaffolding of the cell. “it’s as if someone is in there with a saw, cutting through all the struts and supports, ” Giza says. Calcium inside the cell, moreover, can activate enzymes that can trigger the cell to destroy itself.’
Where do you look for this to happen as the sense of smell downgrades in early Alzheimer’s disease? You look where the rosemary scent gets interpreted within the olfactory network, with its unique vulnerability, within olfactory neurons. If this unique vulnerability happens with the development of Alzheimer’s disease, do long time football multiple concussion injured players exhibiting early dysfunctional Alzheimer’s dementia also suffer olfactory damage as an early indicator?
The winner of the Provost Research Scholarship, Jamie King from the University of Tennessee at Chattanooga, Department of Psychology has broken first ice inferring from the multiple concussion query by determining there is olfactory damage associated with mild traumatic brain injury even after just one concussion. The participants of his study under the supervision of Dr Nicky Ozbek were tested with a scratch and sniff standardized smell test called the University of Pennsylvania Smell Identification Test (UPSIT). ‘ Significant differences were found between groups, namely those in the concussion group did significantly worse than the other volunteer participants. It was found that most people did not perceive any smell loss, even when it was present. Also nearly one quarter of the participants who had experienced a concussion were not aware that they had received a concussion. ‘ What appears to be happening? As the scent sensing starts to fail degrading in the communication inside of its local network other connected networks link down too, is that the early disease pattern? “The brain center for awareness of sense of smell loss has not been well localized but may be in the medial temporal lobe structures that are known to be affected by Alzheimer’s disease,” according to Practical Neurology July/August 2009 author Dr Ronald Devere from Olfactory Testing in the Diagnosis of Alzheimer’s Disease and other Neuro-Degenerative Disorders
I started with smelling the rich summer scent of rosemary to reveal detection of early Alzheimer susceptibility then veering toward the beginning of a screening test for concussions. The sense of smell is the least funded of all the sensory based research, behind vision, behind hearing, behind taste, behind pain. Surprisingly the scent signals are telling us about the unique vulnerability of specific brain zones especially for early detection of Alzheimer’s disease. Instead of smelling salts to arose somebody after a concussion we should be offering a UPSIT sniff and scratch test to compare with their pre-injury smell function UPSIT test, potentially confirming the diagnosis of a concussion. The validity of the olfactory concussion comparison test is a project waiting to happen.
I came across a word yesterday, ubuntu.Which is roughly translated as: to start the sharing of knowledge to everybody’s gain. That is the best I can say about what I am trying to do with writing about concussions. They can happen anywhere to anyone. I believe we can start a better awareness of their biology. I believe one day in the middle of my heart we can grasp the essence of the damage trail with concussions about what happens in the brain, where it happens. I believe we can jam it -influencing, coaxing to slow it down to reestablish a balance within the brain. There is a treatment for concussion -I can feel it in my gut. I just hope I see the day that intervention comes to pass.