Brother, Can you Spare a Dime?

Memories of early life with brain injury conjure the feelings of unwanted, orphan children making the best of their childhood; swinging awkwardly, unwatched, unguided, yet nonetheless playing on a rusted swing set among the overgrowth of a condemned playground.  But time is money, and we all know that cash is king!  The memories of old become polished, understandable, and okay as we move through the stages of recovery.  I will share one quick memory that made me smile today.  At the time, no appreciation or lifting of my anguish occurred.  Now, with the payments afforded through months and months or growth and reflection, I know this thirty seconds of memory reaffirmed whatever it is that makes people everything they can be along the spectrum – from cruel, psychopathic, and all the way through the gradient to the act I experienced that seems almost saintly.

Perhaps four-six months post moderate TBI, I was on my own, as usual, tasked with at least making it on my own to routine appointments.  I even had a notebook with a decision tree.  What decision came next was in writing for my review.  I took the Bay Area Rapid Transit BART train system from Richmond, CA, to downtown San Francisco for my twice weekly psychotherapy appointments with my longtime psychiatrist.  Being out of work and living in the SF Bay Area on SSDI made money a constant threat to my wellbeing.  One impulsive decision and I could not afford groceries – you know the story.  Back to the story at hand, I left for my trip into San Francisco and deposited my last 20 dollars, saw it had loaded on my train ticket, and knew it would get me there and back without a hiccup.  Except with brain injury there is always a hiccup.  Mine came on my return ride home.  BART charges the fare according to the length of your trip, and if you do not have adequate funds on your ticket, an agent will prevent you from leaving the station until the issue is resolved.  I passed my ticket through the gate and the red alert of “insufficient funds” flashed.  Twice.  Then a third time as I moved down the gates, assuming the card reader was the problem.  When a shoulder of mine was pulled with the force enough to turn my body 180 degrees, I looked into the eyes of a weary station agent at the Richmond, CA BART station; Richmond, and I assume it’s BART station, have seen and heard it all.  So, seemed, from the look of this agent that no “story” or promise I had paid earlier when departing would be met with unquestioned trust.  I plead my case; I was certain my 20 dollars had been added, and confirmed to be loaded on my ticket that very morning.  I do not ride BART alone often, and this is my habit – the machine must be stealing my money.  “You have one dollar and forty cents.  I need you to load the balance onto your fare before you can leave the station.”  My emotional lability teetered between shock, anger, fear, and finally settling on the threat that I was being taken advantage of – again.  That was my twenty dollars, please fix this ticket.  I have never been more certain before.  Please, I grunted, people try to take advantage of others all the time, and I am not having it.  “Yes, but I am running your ticket’s history and you never loaded anything on it this morning.  It was last used weeks ago, and the balance is just over a dollar.  You did not put twenty dollars on this ticket.” My body language and speech must have begun to deteriorate noticeably, as they do when I am cognitively taxed.  I knew I was right, and said so again.  After the same explanation, I again stated my memory was correct; that twenty dollars had been taken from me.  “Do you have any problems?” The agent asked, stepping back and relaxing his tone.  “I have a brain injury. Why?”  I said loudly and defensively.  The agent sighed, knowing this was going to be a difficult time to have to involve the BART police.  I wasn’t asking for money, I was asking for my money back.  No measurable amount of seconds passed before a lean, late-thirties aged man simply stuck twenty dollars in my hand and walked through the gate without a word.  Even more, he did this without even a look back towards us; his action was automatic, thoughtless, part of his being and not a calculation between altruism and a chance to preen his pride.  I couldn’t appreciate what a kind gesture this was at the time.  I felt my stolen money had been returned by a passenger who decided to end the public bickering at the gates I was blocking.  Or perhaps he had the money to give, and not the time to spare intervening and simply paying my six or seven dollars fare.

Today I thought about how this was the first time I was asked if I had a brain “problem” by a stranger.  I thought my deficits, if they even amounted to much, were not perceptible.  They were clear as the day, but concealed most of all to myself.  Second, this stranger who passed through without a break in his stride, understanding I felt owed twenty dollars, not simply the fare, knew without more than seeing and hearing the way I carried myself, interacted, repeated questions and answers, and bore a look of confusion that I poorly powdered with a layer of independence and pride.  He knew what a human being is; it is a life exposed to the elements of hate, joy, ecstasy, awe, inspiration, loneliness, wonder, indifference, humor, anger, compassion, and pain of the greatest heights.  I wish him the greatest of heights in his journey walking this earth.

-Sean Dudas

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Explaining Your Brain Injury May Make You Feel Speechless, Yet the Lack of Language to Truly Impart the Experience of Living With Brain Injury is the Root to This Thorn. Until Public Discourse Deepens Definitions, Words Remain Reinforced Windows to Shame and Shut Our Mouths’ Speechless. But We are Not Speechless, We Are Wordless.

Source: Explaining Your Brain Injury May Make You Feel Speechless, Yet the Lack of Language to Truly Impart the Experience of Living With Brain Injury is the Root to This Thorn. Until Public Discourse Deepens Definitions, Words Remain Reinforced Windows to Shame and Shut Our Mouths’ Speechless. But We are Not Speechless, We Are Wordless.

Explaining Your Brain Injury May Make You Feel Speechless, Yet the Lack of Language to Truly Impart the Experience of Living With Brain Injury is the Root to This Thorn. Until Public Discourse Deepens Definitions, Words Remain Reinforced Windows to Shame and Shut Our Mouths’ Speechless. But We are Not Speechless, We Are Wordless.

We are Not Speechless, We Are Wordless.

Each brain injury shares a common nucleus of similar injury symptoms.  Some say the stages of healing and psychologically coming to terms with grief and change are so alike that rehabilitation professionals tend to match up these “newly injured,” or “high functioning adults.”  Stop and remind yourself this:

“If you’ve seen one brain injury, then you’ve seen one brain injury.”

This truth is evidence that each of our stories must be told, heard, and felt – whether publicly or privately, and through any medium that you, your loved ones, caregivers, and any other soul touched by this topic choose to utilize so that our honest expressions can be actually  understood and heard by the often indifferent majority of people.  I will share some of my memories, reflections, some resources, repost others’ blogs, and do my best to tell no lie – even if it is only a lie because I could not find the right words to make it deeply honest.  As Bruce Lee said, “It is easy for me to put on a show and be cocky…to show you some really fancy movement.  But, to express myself honestly. To express yourself honestly, not lying to yourself.  Now that, my friends, is very hard to do.”

Common to every brain injured patient, and often any caregivers, is the misunderstanding and fear surrounding traumatic brain injuries and concussions.  Injured persons are desperate to feel understood, believed in, and treated as if they were the same old person inside.  Yet even after the behavioral, emotional, cognitive, and physical changes present soon after the brain injury, people do not expect that what happens next will be so unexpected.  People like a clear, linear path of recovery to a place the brain was, and will never will be again.  Further, initial brain injuries can seem to be difficult for the patient in certain ways those around them come to recognize.  Yet after initial injury, the brain sets in motion a cascade of neurophysiological responses to scramble metabolism, inflammation, blood and oxygen rates, and hormonal system alterations.  Some patients do not go through much, but many change dramatically, seem to be progressing in ways that later decline, and new organic and trauma related emotional and erratic behavioral changes now accompany the injuries own organic, neuropsychological stages of brain in its survival mode, reprogramming and adapting as best as it can to mimic the previous levels of function a patient may have included as a character trait, or a skill known proudly by others.

Education, experiences with medical providers, insurance, disability, psychosocial effects, and the expansive secondary impact upon caregivers, friends, occupational engagements, and more hold devastating consequence to survivors and their communities, too, for each person lost in our system is lost to us in our society.

It is a scientific puzzle, the brain, and the answer is simply that we do not know enough about what occurs when the brain is injured.  To make this worse, each brain is different, each is injured differently, and each responds to the post-injury event differently.  Plus, we all have lives that vary in socioeconomic group, geographic location, individual health status, and we vary as to the responsibilities and expectations within even community wide social commonalities.  Yet, to make diagnosis neatly wrapped in separate packaging, medical trends consider similar categories of brain injury together, while even the severity of the injury is usually given a point system rating scale.  Strokes, closed head injuries, open head injuries, Mild Traumatic Brain Injury, Moderate TBI, Severe TBI, diffuse axonal injuries, focal injuries, concussion, post concussion syndrome, mild neurocognitive disorder…these may appear categorically similar, but directing similarly looking injuries may not always guide appropriate treatment decisions.  Should I suffer from a gun shot wound to the chest, legs, and stomach, will any hospital funnel you into a “catastrophic bodily injury” treatment center?  Of course not!  The patient with breast cancer, the student athlete with a torn ACL, the man with pancreatitis, and me and my bullet riddled torso in no way are eased by the efficiency of segregating patients in this way.  The brain is everything else.  It is too foreign to the brightest of us, and brain injury, the recovery, and the experience living after any type of brain injury is not generally “alike” enough to pursue efficiency through head versus body injury.  Then there is one other problem.  Even we who suffer a type of brain injury ourselves find it is not easy to explain or describe to others; it almost seems to be a topic deemed unspeakable to everyone around us who will just never empathically feel our innermost turmoil and sensations of the body, mood, and mind.  How can we fix this?

Explaining to someone naive to the experiences survivors of brain injury have encountered is difficult; the social editor inside ourselves leaves us to often hold back from revealing honestly and thoroughly the truly raw and deeply held emotional and experiential intensities.  Recovering and adjusting to life after brain injury is far too isolating enough as it is without feeling speechless when describing our innermost feelings and experiences.  We are not so speechless to describe the experience of brain injury so much as we are wordless – it cannot ever be truly impressed in full spectrum in any typical fashion.  For this reason, we must choose to speak from the honest feelings within us as if no audience is present to interpret and misunderstand; by any medium necessary we must transmit both the facts and the feelings related to traumas; we must engage in self-observation, speak through our somatic awareness, our body’s stress and tensions.  By first willingly perceiving our own visceral sensations, we begin to develop the ways to describe our innermost recesses and trauma.  Whether privately or publicly, by medium of speech, poem, story, art or other expression, we find honesty, break the walls of isolation, and come to regard ourselves and others with compassion.  Gradually, as we rehabilitate and adapt to the changes of brain injury origin, working hard to repair the brain will naturally accompany the cultivation of our heart and the happiness, kindness, and joy of living that escapes too many of us after brain injury.

Survivors of any form of acquired and traumatic brain injury, their caregivers, their loved ones, and others affected or touched by the topic should post stories, share art, share jokes, use any coping skill or strategy to get the truth out.  This will help remind us that we thought we lost our minds, but the impacts of the injury meant our minds also found a place to hide.  It’s not time to hide now.  It is time to just be.

-Sean Dudas

Early intervention and education on diet, rest, activity, and hospital discharge guidelines are crucial for the “injury that attempts to heal with more injury.” Most leave the ED after a head injury event with no warning the brain often continues escalating the cascading, secondary bio physiological injuries; blood flow, ILs, cytokines, inflammatory insults; gate voltage modulation and the toxic increase of glutamate levels, and on and on… brain change usually is unidirectional. Let’s educate and empower ourselves; let’s properly live through recocery; with discipline some factors may mitigate the secondary brain injury state of hell with just enough wellness to keep fighting!

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Brain Neurotrauma: Molecular, Neuropsychological, and Rehabilitation Aspects.

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Chapter 4Pathophysiology of Mild TBI
Implications for Altered Signaling Pathways
Robert A Laskowski, Jennifer A Creed, and Ramesh Raghupathi.

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4.1. INTRODUCTION

Concussions and mild traumatic brain injury (TBI) represent a substantial portion of the annual incidence of TBI aided by the increased reporting of concussions in youth sports, and the increased exposure of soldiers to blast injuries in the war theater. The pathophysiology of concussions and mild TBI consist predominantly of axonal injury at the cellular level and working memory deficits at the behavioral level. Importantly, studies in humans and in animals are making it clear that concussions and mild TBI are not merely a milder form of moderate-severe TBI but represent a separate disease/injury state. Therefore, acute and chronic treatment strategies, both behavioral and pharmacological, need to be implemented based on thorough pre-clinical assessment. The review in this chapter focuses on two under-studied components of the pathophysiology of mild TBI—the role of the c-Jun N-terminal kinase pathway in axonal injury, and the role of the dopaminergic system in working memory deficits.

The growing awareness of the incidence of concussion in contact sports, coupled with the emergence of blast-related injuries in combat fighting, has heightened the urgency to understand the underlying mechanisms of mild brain trauma and devise potential therapeutic interventions. TBI in general, and mild TBI in particular, is considered a “silent epidemic” because many of the acute and enduring alterations in cognitive, motor, and somatosensory functions may not be readily apparent to external observers. Moderate to severe TBI is a major cause of injury-induced death and disability with an annual incidence of approximately 500 in 100,000 people affected in the United States (Sosin et al., 1989; Kraus and McArthur, 1996; Rutland-Brown et al., 2006). However, approximately 80% of all TBI cases are categorized as mild head injuries (Bazarian et al., 2005; Langlois et al., 2006). It is important to note that these approximations are underestimates because they do not account for incidents of TBI in which the person does not seek medical care (Faul et al., 2010). Recent estimates to correct for this underreporting have placed the annual incidence at approximately 3.8 million (Bazarian et al., 2005; Ropper and Gorson, 2007; Halstead and Walter, 2010). The Glasgow Coma Scale (GCS) score, which measures level of consciousness, has been the primary clinical tool for assessing initial brain injury severity in mild (GCS 13–15), moderate (GCS 9–12), or severe (GCS < 8) cases (Teasdale and Jennett, 1974). Although this scoring system serves as a reliable predictor of patient survival (Steyerberg et al., 2008), particularly in the acute phase of trauma and for those patients with more severe head injury (Saatman et al., 2008), it does not necessarily reflect the underlying cerebral pathology because different structural abnormalities can produce a similar clinical picture.

Concussions are a frequent occurrence in contact sports such as football, hockey, lacrosse, and soccer, and increasing evidence suggests that athletes may sustain multiple concussions throughout their career (Bakhos et al., 2010; Bazarian et al., 2005; Grady, 2010; McCrory et al., 2009). Another significant population is soldiers suffering from blast-related injuries, with one in six soldiers returning from combat deployment in Iraq meeting the criteria for concussion (Wilk et al., 2010). Gender factors may also play a role in the epidemiology of concussion. Comparisons of similar sports have yielded the observation that females have nearly twice the rate of concussion compared with males (Dick, 2009; Lincoln et al., 2011). It is important to note that concussed high school males and females self-report different symptoms, with females more often complaining of drowsiness and noise sensitivity, whereas males complain of cognitive deficits and amnesia (Frommer et al., 2011). Furthermore, females also have a higher postconcussion symptom score 3 months postinjury (Bazarian et al., 2010). Two primary complications of concussion are the postconcussion syndrome and second impact syndrome. The postconcussion syndrome is the persistence of concussion-induced symptomatology for greater than 3 months postinjury, presumably because of both neurophysiological and neuropathological processes secondary to the initial concussion (Silverberg and Iverson, 2011).

Second impact syndrome is a condition in which a second head impact is sustained during a “vulnerable period” before the complete symptomatic resolution of the initial impact leading to profound engorgement, massive edema, and increased intracranial pressure within minutes of the impact and resulting in brain herniation, followed by coma and death (Cantu, 1998; Field et al., 2003). It is believed that this vulnerable period is the duration of an injury-induced failure of cerebral blood flow autoregulation (Lam et al., 1997), which can leave the patient highly vulnerable to drastic fluxes and extremes of blood pressure. Second impact syndrome has a morbidity rate of 100% and a mortality rate of 50%, and it is important to note that as of 2001, all reported cases of second impact syndrome had occurred in athletes younger than 20 years of age (McCrory, 2001).

Neurobehavioral symptoms, which often correlate with severity of the TBI, vary in type and duration and are manifested as somatic and/or neuropsychiatric symptoms (reviewed in Riggio and Wong, 2009). Somatic symptoms refer to the physical changes associated with TBI and include headache, dizziness/nausea, fatigue or lethargy, and changes in sleep pattern. Headache is the most commonly reported somatic symptom after mild TBI and is considered acute if resolved within 2 months or chronic if headaches persist for longer than 2 months. Dizziness is another commonly reported symptom of TBI and generally resolves within 2 months but may continue in patients with moderate or severe TBI. Another particularly debilitating symptom is fatigue, likely due to difficulty in initiating or maintaining sleep. Neuropsychiatric sequelae after TBI comprise cognitive deficits and behavioral disorders and are identified in almost all TBI patients for up to 3 months, with a small percentage exhibiting persistent (months—years) symptoms. Cognitive deficits are characterized by impaired attention, memory, and/or executive function and may cause the patient to become irritable, anxious, or depressed. Cognitive deficits in cases of mild TBI generally resolve within days and do not have to be associated with loss of consciousness and posttraumatic amnesia. Behavioral manifestations after TBI include personality changes, depression, and anxiety. Personality changes describe aggression, impulsivity, irritability, emotional lability, and apathy. Major depression is one of the most frequently reported behavioral sequelae of TBI, accounting for approximately 25% to 40% of cases of moderate-to-severe TBI (Riggio and Wong, 2009).

Collectively, these observations underscore the need to develop age-, sex-, and injury severity—appropriate animal models of mild TBI and concussions. The following review describes the current state of knowledge of the pathophysiology of mild TBI/concussions, with particular attention to axonal injury and cognitive deficits.

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4.2. EXPERIMENTAL APPROACHES TO STUDYING CONCUSSIONS

The symptomatology associated with concussion appears to be primarily functional in nature because standard neuroimaging studies reveal no structural abnormalities; however, postmortem analyses of brains from patients who had sustained a recent mild TBI, but had died from nontraumatic causes, showed evidence of axonal injury (Blumbergs et al., 1994, 1995). Specialized functional magnetic resonance imaging has revealed decreases in cortical blood flow to the mid-dorsolateral prefrontal cortex during the acute postconcussive period in athletes challenged in a working memory task as well as activation patterns that correlate with symptom severity and recovery (Chen et al., 2004), whereas diffusion tensor imaging has also detected evidence of microstructural white matter and axonal injuries in some cases of prolonged deficits (Arfanakis et al., 2002; Niogi et al., 2008; Smits et al., 2010; Wilde et al., 2008). Furthermore, electroencephalography and transcranial magnetic stimulation studies have determined that acute and long-term electrophysiological changes in brain activity can occur in the absence of overt neuropsychological impairment (De Beaumont et al., 2007a, 2007b; Gosselin et al., 2006).

A concussion may be caused by either a direct blow to the head (contact forces, Figure 4.1a) or by a blow to elsewhere on the body with the forces being subsequently transmitted to the brain (inertial forces, Figure 4.1b) (McLean, 1996; Teasdale and Matthew, 1996). Rotational forces around a defined axis are thought to be responsible for damage to deep white matter tracts, resulting in a diffuse axonal injury as well as causing damage to deep gray matter nuclei (McLean, 1996; Thibault and Gennarelli, 1990). A third possible force, the presumable basis of blast trauma, is based on the stereotactile theory, which posits that as a result of the interplay between the spherical shape of the skull and the fact that brain tissue has the same density on concentric planes, the pressure waves created by skull—brain interactions or skull vibrations may propagate through brain tissue as a spherical wave front, resulting in a more focused and direct energy reaching deeper brain structures (Willinger et al., 1996).

FIGURE 4.1. Representation of contact (a) and rotational forces (b) associated with traumatic brain injury.
FIGURE 4.1

Representation of contact (a) and rotational forces (b) associated with traumatic brain injury.
Animal models of TBI have been developed in the ferret, cat, pig, and monkey but the most common and developed model is the rodent (Gennarelli, 1994). Two models predominate to elucidate mechanisms of diffuse or concussive brain injury—the midline fluid-percussion model (Dixon et al., 1987) and the impact-acceleration model (Marmarou et al., 1994). Both models were originally characterized in the rat and demonstrate characteristics of human TBI such as cognitive dysfunction (Beaumont et al., 1999; Lyeth et al., 1990) and axonal injury (reviewed in Buki and Povlishock, 2006). More recently, concussive brain injury has been modeled in mice (Laurer et al., 2001; Longhi et al., 2005; Spain et al., 2010; Tang et al., 1997a, 1997b; Zohar et al., 2003). Injury induced by a weight drop, fluid percussion, or a modified cortical impact device resulted in diffuse neurodegeneration in the cortex and hippocampus and βAPP(+) intraaxonal swellings in the thalamus, corpus callosum, and external capsule (Longhi et al., 2005; Spain et al., 2010; Tang et al., 1997b; Tashlykov et al., 2007). Closed-head injury in mice resulted in long-term behavioral dysfunction characterized by learning deficits, depressive behavior, and increased passive avoidance (Milman et al., 2005; Tang et al., 1997a; Spain et al., 2010; Zohar et al., 2003). In contrast, impact to the intact skull using a silicone-tipped indenter only resulted in a transient deficit in motor function with no effect on spatial learning ability (Laurer et al., 2001, 2005). Although these animal models reflect the acute neurochemical, microscopic, and anatomical pathophysiology of concussive brain trauma, they do not appear to model the hallmark of concussion—transient neurologic (cognitive) dysfunction. Impact to the intact skull of mice over the midline suture resulted in spatial learning and working memory deficits only in the first 3 days after trauma (Creed et al., 2011). Traumatic axonal injury was observed up to 3 days postinjury and degenerating axons at 14 days postinjury. These structural alterations in injured axons were accompanied by functional deficits that manifested as reductions in compound action potential and decreased retrograde transport, which were present up to 2 weeks postinjury. Further evidence of diffuse brain injury arose from the observation of cortical edema over the first 24 hours postinjury and neuronal degeneration in the cortex and hippocampus up to 3 days postinjury.

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4.3. AXONAL INJURY AFTER MILD TBI

Traumatic axonal injury is triggered by the inertial forces of trauma to the brain, resulting in subsequent structural and subcellular changes within the axon cylinder (Buki and Povlishock, 2006). One of the initial changes is altered axolemmal permeability because of focal microscopic mechanoporation of the axolemma and was first observed as influx of the normally excluded protein, horseradish peroxidase, after head injury (Pettus et al., 1994; Pettus and Povlishock, 1996). These microscopic holes may provide a route for intraaxonal calcium influx, leading to calpain activation (Buki et al., 1999; Saatman et al., 1996). Calpain activation may effect structural alterations to the axonal cytoskeleton leading to disruption of both anterograde and retrograde transport and eventual swellings in contiguous axons and finally secondary axotomy (Buki and Povlishock, 2006; Creed et al., 2011; Shojo and Kibayashi, 2006). Direct evidence of retrograde transport impairment using Fluoro-Gold transport in the brain after a traumatic injury was recently demonstrated (Creed et al., 2011). In part, disruption of axonal transport may be mediated by neurofilament compaction, which occurs as a result of dephosphorylation and has been recognized as another prominent characteristic of axonal injury after TBI (Chen et al., 1999; Christman et al., 1994; Creed et al., 2011; Povlishock et al., 1997).

The c-Jun N-terminal kinases (JNKs) are a subfamily of mitogen-activated protein kinases that play important roles in the central nervous system, in both physiological (neurite outgrowth and extension, brain development and neuronal repair) and pathological conditions (apoptosis, axonal injury) (Herdegen and Waetzig, 2001; Kuan et al., 2003; Waetzig and Herdegen, 2003; Yang et al., 1997). JNK activation has been observed in experimental models of TBI in both neurons (Raghupathi et al., 2003; Ortolano et al., 2009; Otani et al., 2002) and axons (Raghupathi et al., 2003) and in humans (Ortolano et al., 2009).

Their ability to participate in and also be activated by cytoskeletal changes allows JNK to play an important role in dynamic neurite outgrowth and elongation during brain development (Waetzig and Herdegen, 2005). Importantly, JNK activation has been implicated in axonal injury after trauma in vivo (Broude et al., 1997; Raghupathi et al., 2003; Raivich et al., 2004) and in vitro (Cavalli et al., 2005; Verhey et al., 2001). Direct phosphorylation of the kinesin-1 heavy chain subunit by activated JNK in the squid axoplasm led to the inhibition of binding between kinesin-1 and axonal microtubules and subsequent fast axonal transport (Morfini et al., 2006). Interestingly, this disruption in axonal transport appeared to be mediated by the neuron-specific JNK3 isoform (Morfini et al., 2009), which may explain the observed protective effect of genetic deletion of the JNK3 isoform after axotomy of dopaminergic neurons (Brecht et al., 2005).

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4.4. WORKING MEMORY DEFICITS AND DOPAMINERGIC SIGNALING IN MILD TBI

Working memory deficits are a major complaint of patients suffering from TBI with transient deficits after mild TBI/concussions and permanent morbidity from severe TBI (Mayers et al., 2011; Gorman et al., 2012; McAllister et al., 2001; Slovarp et al., 2012; Theriault et al., 2011). In rats and mice, working memory deficits have been documented and appear not to be dependent on the location of the impact or the type of model used. Thus, contusive trauma or fluid-percussion injury either over the frontal cortices or the parietal cortex (Hamm et al., 1996; Hoane et al., 2006; Hoskison et al., 2009; Vonder Haar et al., 2011) all resulted in significant long-term working memory deficits in the adult rat. Conversely, closed-head midline cortical contusion injury that impacts the skull midway between Bregma and Lambda is capable of producing a working memory deficit in adult male mice tested on days 1–3 postinjury, but that has resolved by days 7–9 postinjury (Creed et al., 2011).

Working memory is an organism’s ability to transiently maintain information in an active and available form over a time delay. It is the mental chalkboard that allows for successful interactions within an ever-changing environment by permitting one to manipulate and actively use the stored information to apply it to a current situation for goal-directed or problem-solving purposes. Working memory relies on the appropriate interactions of a distributed network of brain regions, though the primary region of integration appears to be the prefrontal cortex (PFC). The cellular activity underlying working memory is based on the activity of neurons after the withdrawal of a prior stimulus or event. Neurons within the prefrontal cortex have “memory fields” or the representation of a target stimulus to which a neuron fires maximally (Funahashi et al., 1989). Working memory requires a finely tuned balance of excitatory and inhibitory inputs into and within the PFC. In animals, mild TBI induces a hypoexcitable brain state in which the evoked population excitatory postsynaptic potential is significantly decreased compared with uninjured animals followed by a period of hyperexcitability (Ding et al., 2011). Sanders and colleagues (2001) noted that an fluid-percussion-induced mild TBI over the right parietal cortex of male rats caused reductions of the slope and increases in the latency of vibrissa-evoked potentials 3 days postinjury, whereas alterations in presynaptic neuronal function have also been observed as early as 1 hour postinjury in adult male rats (Reeves et al., 2000).

Pyramidal, excitatory neurons act in concert with inhibitory interneurons; this system is modulated by dopaminergic afferents to the prefrontal cortex from the ventral tegmental area (Durstewitz and Seamans, 2002). These dopamine afferents form symmetric synapses on the dendritic spines of pyramidal neurons, which in turn contain the D1 dopamine receptor subtype (Charuchinda et al., 1987; Lidow et al., 1991; Smiley et al., 1994). Expression of the D1 receptor increased in the PFC as early as 3 hours and remained elevated up to 3 days after contusive brain trauma (Kobori and Dash, 2006). In contrast, in the striatum, the binding properties of the D1 receptor decreased in the acute posttraumatic period but increased in the subacute period, with no concomitant change in the level of expression (Henry et al., 1997; Wagner et al., 2009). Nonspecific dopamine agonists such as methylphenidate (Newsome et al., 2009; Wagner et al., 2007) and amantadine (Dixon et al., 1999; Meythaler et al., 2002) have ameliorated TBI-induced cognitive deficits. In a model of moderate brain trauma, the D1 receptor antagonist SCH23390 attenuated working memory deficits (Kobori and Dash, 2009), whereas after concussive TBI, the efficacy of SCH23390 was augmented by a coadministration of the D2 receptor antagonist sulpiride (Tang et al., 1997a, 1997b). In contrast, in a model of concussion in adolescent rats, we observed that a partial agonist of the D1 receptor (SKF38393) almost completely restored working memory function in brain-injured rats (unpublished observations). These data, while implicating the dopamine system in posttraumatic working memory deficits, underscore the complicated nature of the response of the brain to differing severities of injury.

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4.5. CONCLUSION

Concussions and mild TBI represent a significant component of the spectrum of TBI-associated syndromes. Accumulating evidence suggests that the pathophysiology of mild TBI may pose questions not addressed over the years in models of moderate-to-severe TBI. Although the cellular manifestation of axonal injury may be transient in mild TBI, deficits in axonal function may be present over a longer period postinjury. Similarly, alterations in dopaminergic signaling may follow a different trajectory than what has been reported in more severe cases and treatment with dopaminergic agents may have to take into account the severity of the injury. These observations underscore the importance of continued studies in mild TBI.

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ACKNOWLEDGMENT

This work is supported, in part, by grants from the National Institutes of Health NS06517 and the Veteran’s Administration.

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INTRODUCTION
EXPERIMENTAL APPROACHES TO STUDYING CONCUSSIONS
AXONAL INJURY AFTER MILD TBI
WORKING MEMORY DEFICITS AND DOPAMINERGIC SIGNALING IN MILD TBI
CONCLUSION
ACKNOWLEDGMENT
REFERENCES
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Symptoms associated with mild traumatic brain injury and concussion: the role of bother.

Symptoms associated with mild traumatic brain injury/concussion: the role of bother.
Bergman K, et al. J Neurosci Nurs. 2013. PMID 23558978 [PubMed – indexed…

Abstract
Traumatic brain injury (TBI) affects 1.4 million Americans annually, and mild TBI (MTBI) accounts for approximately 75% of those injured. For those with mild injury who seek treatment in an emergency department, there is inconsistency in the management and follow-up recommendations. Approximately, 38% of patients treated in the emergency department for MTBI are discharged with no recommendations for follow-up. In addition, there are an unknown number of persons with MTBI who do not seek healthcare after their injury. Persons with MTBI are, for the most part, managing their concussion symptoms on their own. The purpose of this study was to describe the symptom experience for persons with mild TBI and identify whether there was an association between being bothered by symptoms and self-management of symptoms. The sample for this study included 30 persons with MTBI and a 30-person comparison group. Results indicate that persons within 3 months of their MTBI report an average of 19 symptoms, whereas the comparison group reported six symptoms, and that the most frequently reported symptoms are not always the symptoms rated as most severe or most bothersome. Persons with MTBI reported their most common symptoms to be headache (n = 25, 83%), feeling tired (n = 24, 80%), difficulty thinking and being irritable (each n = 22, 73%), dizziness, trouble remembering, and being forgetful (each n = 21, 70%). There is a significant relationship between overall reports of being bothered by symptoms and the use of symptom management strategies (F = 8.322, p = .008). Persons are more likely to use symptom management strategies when they are bothered by the symptoms. Nurses can assist with symptom self-management by providing simple symptom management strategies to assist with the symptom management process. Early symptom management for the MTBI population may improve the outcomes such as return to work and role functions, for this population.

Microenvironment changes in mild traumatic brain injury.

Review article
Kan EM, et al. Brain Res Bull. 2012.
Show full citation
Abstract
Traumatic brain injury (TBI) is a major public-health problem for which mild TBI (MTBI) makes up majority of the cases. MTBI is a poorly-understood health problem and can persist for years manifesting into neurological and non-neurological problems that can affect functional outcome. Presently, diagnosis of MTBI is based on symptoms reporting with poor understanding of ongoing pathophysiology, hence precluding prognosis and intervention. Other than rehabilitation, there is still no pharmacological treatment for the treatment of secondary injury and prevention of the development of cognitive and behavioural problems. The lack of external injuries and absence of detectable brain abnormalities lend support to MTBI developing at the cellular and biochemical level. However, the paucity of suitable and validated non-invasive methods for accurate diagnosis of MTBI poses as a substantial challenge. Hence, it is crucial that a clinically useful evaluation and management procedure be instituted for MTBI that encompasses both molecular pathophysiology and functional outcome. The acute microenvironment changes post-MTBI presents an attractive target for modulation of MTBI symptoms and the development of cognitive changes later in life.

Copyright © 2012 Elsevier Inc. All rights reserved.
PMID 22289840 [PubMed – indexed for MEDLINE

Research Reports – The role of cognitive reserve in recovery from traumatic brain injury

J Head Trauma Rehabil. 2017 May 17. doi: 10.1097/HTR.0000000000000325. [Epub
ahead of print]

Steward KA(1), Kennedy R, Novack TA, Crowe M, Marson DC, Triebel KL.

OBJECTIVE: To examine whether cognitive reserve (CR) attenuates the initial
impact of traumatic brain injury (TBI) on cognitive performance (neural reserve)
and results in faster cognitive recovery rates in the first year postinjury
(neural compensation), and whether the advantage of CR differs on the basis of
the severity of TBI.
SETTING: Inpatient/outpatient clinics at an academic medical center.
PARTICIPANTS: Adults with mild TBI (mTBI; n = 28), complicated mild TBI (cmTBI; n
= 24), and moderate to severe TBI (msevTBI; n = 57), and demographically matched
controls (n = 66).
DESIGN: Retrospective, longitudinal cohort assessed at 1, 6, and 12 months
postinjury.
MAIN MEASURES: Outcomes were 3 cognitive domains: processing speed/executive
function, verbal fluency, and memory. Premorbid IQ, estimated with the Wechsler
Test of Adult Reading, served as CR proxy.
RESULTS: Higher premorbid IQ was associated with better performance on cognitive
domains at 1 month postinjury, and the effect of IQ was similarly beneficial for
all groups. Cognitive recovery rate was moderated only by TBI severity; those
with more severe TBI had faster recovery in the first year.
CONCLUSION: Results support only the neural reserve theory of CR within a TBI
population and indicate that CR is neuroprotective, regardless of the degree of
TBI. Higher premorbid CR does not allow for more rapid adaptation and recovery
from injury.