The overall goal of my research was to advance our understanding of the potential for novel compliant flooring systems to reduce the risk for fall-related injuries in older adults, including fall-related traumatic brain injury (TBI). This entailed an assessment of how these floors affect the competing demands of fall-related TBI – impact severity attenuation in concert with minimal concomitant impairments to balance control and postural stability. Two studies are included as part of this thesis. The first study used a mechanical drop tower to assess the effects of four traditional flooring systems and six novel compliant flooring conditions on the impact dynamics of a surrogate headform during the impact phase of simulated ‘worst- case’ head impacts. The second study entailed an assessment of the effect of two traditional and three novel compliant floors on the initial phase of the compensatory balance reactions of older adult men and women living in a residential-care facility environment following an externally induced perturbation using a tether-release paradigm. Overall, this thesis demonstrates that novel compliant floors substantially attenuate the forces and accelerations applied to the head during simulated worst- case impacts when compared to traditional flooring surfaces such as vinyl and carpet with underpadding. These benefits are achieved without compromising indices of balance control, supported by the finding that parameters characterizing early compensatory balance reactions were unaffected by the novel compliant floors tested. This work supports the introduction of pilot installations of novel compliant flooring systems into environments with high incidences of falls to test their effectiveness at reducing fall-related injuries in clinical settings.

Traumatic brain injury (TBI) results from a physical insult to the head and often results in temporary or permanent brain dysfunction. However, the cellular pathology remains poorly understood and there are currently no clinically effective treatments. The overall goal of this work was to develop and characterize a novel three-dimensional (3-D) in vitro paradigm of neural trauma integrating a robust 3-D neural co-culture system and a well-defined biomechanical input representative of clinical TBI. Specifically, a novel 3-D neuronal-astrocytic co-culture system was characterized, establishing parameters resulting in the growth and vitality of mature 3-D networks, potentially providing enhanced physiological relevance and providing an experimental platform for the mechanistic study of neurobiological phenomena. Furthermore, an electromechanical device was developed that is capable of subjecting 3-D cell-containing matrices to a defined mechanical insult, with a predicted strain manifestation at the cellular level. Following independent development and validation, these novel 3-D neural cell and mechanical trauma paradigms were used in combination to develop a mechanically-induced model of neural degeneration and reactive astrogliosis. This in vitro surrogate model of neural degeneration and reactive astrogliosis was then exploited to assess factors influencing neural stem cell (NSC) survival and integration upon delivery to this environment, revealing that specific factors in an injured environment were detrimental to NSC survival. This work has developed enabling technologies for the in vitro study of neurobiological phenomena and responses to injury, and may aid in elucidating the complex biochemical cascades that occur after a traumatic insult. Furthermore, the novel paradigm developed here may provide a powerful experimental framework for improving treatment strategies following neural trauma, and therefore serve as a valid pre-animal test-bed.

With over 50,000 deaths and 80,000 disorders annually in the United States resulting from traumatic brain injury (TBI), there is a demand for improved therapeutic strategies. Cell transplantation offers the potential to treat TBI by targeting multiple mechanisms in a sustained fashion. However, efforts are needed to improve survival and integration of transplanted cells, and ultimately enhance functional recovery. Using tissue engineering strategies, we aimed to mimic key aspects of fetal tissue grafts by combining neural stem cells with a fibronectin or laminin based scaffold that could be delivered to the injured brain in a minimally invasive fashion. We found that the incorporation of extracellular matrix proteins into a cell transplantation paradigm led to improved donor cell survival and restored cognitive ability for treated animals. To begin to examine how fibronectin and laminin mediate these improvements, we first examined the endogenous role of these two proteins in the injured brain. Using a clinically-relevant model of TBI, we found both proteins are increased in the injured brain at acute time points. The spatial localization of fibronectin and laminin with specific support cells in the brain suggests a role for these proteins in repair, warranting further investigation. Using conditional plasma fibronectin knockout animals, we found that fibronectin is neuroprotective to the traumatically injured brain. Specifically, injured fibronectin knockout animals had more severe motor and cognitive deficits, increased cell death, and decreased retention of phagocytic cells compared to injured wild type animals. Thus, we have identified novel therapeutic treatments for TBI which utilize tissue engineered transplants and/or exploit endogenous repair mechanisms for fibronectin.

SAMMANFATTNING Bakgrund Traumatisk skallskada drabbar relativt många och leder till personligt lidande och finansiell belastning för individ och samhälle då majoriteten får en svår till medelsvår funktionsnedsättning efter vårdtiden. På 1970-talet påvisades ett signifikant samband mellan högt ICP och sekundära hjärnskador. I studier där ICP >20 mmHg har förekommit kunde signifikant sämre utfall ses. Syfte Syftet med studien var att med hjälp av omvårdnadsprocessen observera intensivvårdssjuksköterskans identifiering och vidtagande av omvårdnadsåtgärder vid ett högt ICP samt utvärdera de utförda omvårdnadsåtgärderna.  Metod Prospektiv tvärsnittsundersökning, där sju intensivvårdssjuksköterskor och fem patienter observerades med hjälp av ett observationsformulär. Resultat 51(73 %) av de höga ICP normaliserades inom en minut och intensivvårdssjuksköterskan uppskattades ha observerat högt ICP i 50(71 %) av tillfällena inom en minut. 19(27 %) tillfällen observerades inte och 11(65 %) av omvårdnadsåtgärderna skedde inom en minut. Omvårdnadsåtgärder som utfördes var administrering av bolusdos med läkemedel (35 %) eller dränera likvor (35 %). Efter utförd omvårdnadsåtgärd normaliserades högt ICP inom en till två minuter, 7(41 %), och 4(24 %) normaliserades inom två till tre minuter. Slutsats Majoriteten av tillfällena med högt ICP uppmärksammades inom en minut och vanligast förkommande omvårdnadsåtgärderna var administrering av bolusdos sederande läkemedel eller dränera likvor. Av de tillfällen med intrakraniell hypertension som inte blev observerade var enbart ett par tillfällen ihållande i längre än en minut och samtliga normaliserades spontant inom två minuter. Intensivvårdssjuksköterskorna identifierade och effektivt åtgärdade intrakraniell hypertension snabbt, vilket kan bidra till ett bättre utfall för patienterna. / ABSTRACT Background Due to traumatic brain injury a financial burden is placed on the individual as well as the society and personal suffering also occurs. A significant correlation between elevated ICP and secondary injury was found in the 1970s. Significantly worse outcome was found in a numerous of studies where ICP >20mmHg occurred. Objective The aim of this study was to observe intensive care nurses nursing interventions and its efficiency to decrease ICP by using Orem’s Self-care deficit theory. Methods A prospective observational study. Seven intensive care nurses and five patients were observed. Results 51(73%) of the observed ICP >20mmHg were normalized within the minute. The intensive care nurses were estimated to have observed an on-going intracranial hypertension in 50(71 %) within the minute. 19(27 %) went unnoticed and 11(65 %) of the nursing interventions were executed within the minute. Nursing interventions executed were administration of a sedative (35 %), drainage of cerebrospinal fluid (35 %). Elevated ICP was normalized in 7(41 %) within two minutes and 4(24 %) within three minutes due to the nursing intervention. Conclusion Intensive care nurses noticed the majority of occasions with elevated ICP within one minute. The most commonly used nursing intervention was to administrate a sedative or to drain cerebrospinal fluid. All of the elevated ICP that went unnoticed normalized spontaneously within two minutes. The fast identification of and treated intracranial hypertension are likely to have contributed positively in the patient’s outcome.

Concussion affects the adolescent population in large numbers, primarily because of the popularity of team sports that are played in middle and high school. This adolescent age group is more susceptible to the adverse effects of concussion due to physiological immaturity, and recovery for this population takes longer than in adults. Speech-language pathologists, who are trained to treat cognitive-communication deficits, are present in the majority of school systems throughout the United States, and could be a useful resource to manage and treat students who incur concussion. However, speech-language pathologists historically have not treated students with concussion, and may not be receiving adequate education regarding concussion in graduate programs. This study sought to ascertain the education, training, and experience regarding concussion of speech-language pathologists in Texas secondary schools. Anonymous survey responses were collected via an Internet survey platform, yielding 49 respondents for the final data pool. The answers provided by these respondents indicate Texas speech-language pathologists are not yet receiving adequate concussion education and training. Respondents reported low confidence levels in several key areas of concussion knowledge, and doubt regarding the speech-language pathologist's role in managing concussion. Recommendations include concussion-targeted graduate school curriculum as an extension of traumatic brain injury curriculum, increased continuing education efforts by ASHA regarding concussion and the speech-language pathologist's role in treating concussion, and further advocacy by ASHA for speech-language pathologists to be part of concussion management teams based in schools. / text

The purpose of this study was to examine the extent to which learning and recall are facilitated by semantic and phonological targets. A list-learning paradigm was administered to 10 individuals with a history of traumatic brain injury. Participants were asked to recall and identify words that were present on the list. The lists consisted of semantically related associate words and phonologically related associate words. Participants recalled significantly more semantically related associates than phonological associates. Demographic factors such as age, time-post injury, and educational attainment did not have a significant effect on the recall ability for either word target type. Word recognition ability also was not influenced by target type. The results of this study found adults with TBI use a semantic network following brain injury and that semantic targets are more beneficial for recall than phonological targets. / text

Learning and memory impairments are among the most common and enduring cognitive consequences of traumatic brain injury (TBI). Researchers have yet to reach a consensus with regard to the basic cognitive mechanism underlying new learning and memory disturbances after TBI. The purpose of the present study was to investigate the current views regarding the cognitive processes thought to explain impairments in verbal learning and memory subsequent to brain injury. Specifically, this study sought to examine the roles of the central executive component of working memory and processing speed in verbal learning ability following TBI. Latent variable structural equation modeling (SEM) was used to analyze the data of 70 post-acute care TBI patients between the ages of 16 and 65, who completed a full neuropsychological evaluation. Results indicated that verbal learning and memory difficulties following TBI were explained primarily in terms of the central executive aspects of working memory, after accounting for the relative contributions of processing speed in the model. The direct effect of processing speed on verbal learning and memory was not significant when working memory was taken into account in the model. Rather, the effects of processing speed on verbal learning ability were largely indirect through the central executive component of working memory. Results highlight the importance of both working memory and processing speed in supporting verbal learning and memory processes after TBI. Practical implications for targeting remediation efforts and directing approaches to memory rehabilitation are discussed in light of the study’s findings. / text

La prévalence des troubles du sommeil et de douleur chronique est élevée chez le patient ayant subi un traumatisme crânien cérébral léger (TCCL). L’interaction entre ces plaintes est suggérée chez les patients avec un TCCL mais son étiologie reste encore peu connue. Les résultats de recherche présentés dans le premier article de cette thèse suggèrent que les patients avec un TCCL qui souffrent de douleur ont une modification des ondes cérébrales durant leur sommeil, ce qui pourrait expliquer en partie comment les deux symptômes interagissent. De plus, la douleur, surtout si associée à des troubles de l’humeur, semble jouer un rôle majeur dans la persistance des symptômes post-commotionnels. Le deuxième article de cette thèse décrit une exacerbation des symptômes post-commotionnels chez le patient ayant eu un TCCL et souffrant de douleur. La persistance ou l’apparition de la douleur chronique à long terme serait prédite par le polymorphisme val66met du gène brain-derived neurotrophic factor (BDNF). Une étude subséquente, présentée dans le troisième article, nous a permis d’approfondir les bases génétiques et cellulaires du rôle du BDNF dans la persistance des symptômes post-commotionnels. Des polymorphismes fréquents dans le gène BDNF ont révélé des variantes liées au mauvais pronostic suite à un TCCL. De plus, l’analyse de cellules extraites de patients ayant subi un TCCL démontrent que l’expression de la protéine BDNF peut être modifiée chez le patient de génotype met66 et ayant subi un TCCL, lui conférant ainsi un rôle neuroprotecteur potentiel. En résumé, nous avons tenté de démontrer dans cette thèse que la douleur suite à un TCCL joue un rôle important dans les perturbations du sommeil et dans la persistance des symptômes post-commotionnels. Une prédisposition génétique pourrait contribuer à expliquer le mauvais pronostic et la chronicité des symptômes post-commotionnels suite à un TCCL. / Mild traumatic brain injury (MTBI) is a major public health concern as patients are left, amongst other symptoms, with sleep complaints and chronic pain. An interaction between these symptoms is suggested. For instance, a night of poor sleep is usually followed by hypersensitivity to pain and chronic pain always leads to sleep complaints. This interaction is suggested following an MTBI, however, data sustaining that hypothesis are still lacking. Data from the first article suggest that pain and other post-concussion symptoms are correlated with sleep-wake disturbances post-MTBI. MTBI patients with pain have more rapid electroencephalographic (EEG) waves during sleep than those without pain. This may suggest that there is an intrinsic physiological relationship between the two complaints. Moreover, pain seems to play an important role in the persistence of post-concussive symptoms. The second article of this thesis describes and details the exacerbation of post-concussive symptoms in the presence of pain following MTBI. The val66met polymorphism in the Brain-derived neurotrophic factor (BDNF) gene is an important predisposing factor for chronic pain. Lastly, a subsequent study, presented in the third article details the genetic and cellular basis of the role of BDNF in the persistence of post-concussive symptoms. Common polymorphisms in the BDNF genes were genotyped and revealed variants related to post-concussive symptoms following MTBI. Moreover, protein expression studies in lymphoblast cells of MTBI patients showed a modified expression of BDNF with the met genotype that might be neuroprotective. In summary, this thesis first shows that pain contributes to sleep-wake disturbances following MTBI and that the chronicity of post-concussive symptoms, including chronic pain, may be dependent on polymorphisms in the BDNF gene.

Atliktas perspektyvusis stebėjimo tyrimas, kurio metu buvo tirti sunkią galvos smegenų traumą patyrę vaikai, gydyti KMUK Vaikų intensyviosios terapijos skyriuje. Pacientų būklė pagal GBS vertinta išvykstant iš gydymo įstaigos ir po šešių mėnesių. Darbo tikslas Nustatyti sunkią galvos smegenų traumą patyrusių vaikų ligos baigčių prognozinius veiksnius. Darbo uždaviniai 1. Įvertinti ankstyvas ir vėlyvas sunkią galvos traumą patyrusių vaikų ligos baigtis. 2. Nustatyti sunkią galvos traumą patyrusių vaikų vidinio kaukolės slėgio ir smegenų perfuzinio slėgio ryšį su ligos baigtimis. 3. Nustatyti sunkią galvos traumą patyrusių vaikų traumos pobūdžio ryšį su ligos baigtimis. 4. Nustatyti paciento būkės vertinimo skalių ir laboratorinių tyrimų kritines reikšmes ir jų prognozinę vertę. 5. Nustatyti laboratorinių tyrimų kritines reikšmes ir jų prognozinę vertę. Išgyveno 80,5 proc. sunkią galvos smegenų traumą patyrusių vaikų. Išvykstant iš gydymo įstaigos 50 proc. pacientų, o po šešių mėnesių – 24,2 proc. pacientų traumos baigtis buvos bloga. Įtakos traumos baigtims turėjo kraujavimas po kietuoju smegenų dangalu, smegenų edema, kaukolės kaulų lūžiai. Nustatytos laktatų, gliukozės kiekio kraujo serume, vaikų traumų skalės, Glazgo komų skalės ir vaikų mirštamumo indekso 2 kritinės reikšmės, prognozuojančios mirtį, blogą baigtį išvykstant iš gydymo įstaigos ir po šešių mėnesių. Dekompresinė kraniotomija, atlikta, kai VKS = 24,5 mmHg,o SPS = 46.5 mmHg ligos baigčių nepakeitė. / The prospective observational study involved children after severe traumatic brain injury treated in Pediatric Intensive Care Unit of Kaunas University of Medicine Hospital. The outcome according to Glasgow Outcome Scale was assessed on discharge and after six months The aim of the study was to determine the prognostic factors in children after severe traumatic brain injury. The objectives of the study: 1. To evaluate early and late outcomes in children after severe traumatic brain injury 2. To evaluate the relation of intracranial pressure and cerebral perfusion pressure with outcome in children after severe traumatic brain injury. 3. To evaluate the relation between type of injury and outcome. 4. To determine the threshold values for trauma scoring scales and to evaluate their prognostic significance. 5. To determine the threshold values for laboratory findings and to evaluate their prognostic significance. The survival rate was 80.5 %.half of patients had bad outcome on discharge and 24.4 % – had bad outcome after six months. The prognostic factors of outcome for children after severe traumatic brain injury were subdural hemorrhage, cerebral edema and skull fracture. Threshold values of Pediatric Trauma Score, Glasgow Coma Score and Pediatric index of Mortality 2 for death and bad outcomes on discharge and after six months were ascertained. Decompressive craniectomy performed at ICP ≥ 24.5 mmHg, CPP ≤ 46.5 mmHg had no impact on outcome in children after severe traumatic... [to full text]

Šiuo tyrimu siekta įvertinti, kaip keičiasi vaikų po sunkaus ir vidutinio sunkumo trauminio galvos smegenų sužalojimo būklė taikant kineziterapiją ankstyvuoju reabilitacijos etapu bei nustatyti veiksnius, kurie labiausiai įtakoja vaikų po traumos pažintinių funkcijų ir motorikos atsigavimą. Tyrimo uždaviniai: 1. Įvertinti vaikų po sunkaus ir vidutinio sunkumo trauminio galvos smegenų sužalojimo pažintinių funkcijų ir motorikos sutrikimus ankstyvojo reabilitacijos etapo pradžioje. 2. Įvertinti vaikų po sunkaus ir vidutinio sunkumo trauminio galvos smegenų sužalojimo pažintinių funkcijų ir motorikos kitimą ankstyvajame reabilitacijos etape taikant individualizuotą kineziterapiją. 3. Nustatyti veiksnius, turinčius įtakos vaikų po sunkaus trauminio galvos smegenų sužalojimo pažintinių funkcijų bei motorikos atsigavimui ankstyvajame reabilitacijos etape ir įvertinti jų prognozinę vertę. Atlikus tyrimą nustatyta, kad vaikams po sunkaus ir vidutinio sunkumo trauminio galvos smegenų sužalojimo ankstyvajame reabilitacijos etape stebimi motorikos (raumenų tonuso, raumenų jėgos, judesių koordinacijos) ir pažintinių funkcijų (sąmonės) sutrikimai sąlygoja šių vaikų hipokinezę bei savarankiškos veiklos sutrikimus. Individualizuota kineziterapija, taikoma vaikams po trauminio galvos smegenų sužalojimo ankstyvajame reabilitacijos etape, daugumai ligonių ženkliai pagerina jų savarankiškumą, tačiau pusei vaikų po sunkaus trauminio galvos smegenų sužalojimo ankstyvojo reabilitacijos... [toliau žr. visą tekstą] / Aim of the study – to establish the factors influencing the recovery of cognitive and motor functions during application of physical therapy in ESR among children suffering severe and moderate TBI. Objectives: 1. To evaluate the cognitive and motor disorders at baseline (start of ESR) among children suffering severe and moderate TBI. 2. To evaluate the changes of cognitive and motor functions applying personally-adjusted physical therapy during ESR for children suffering severe and moderate TBI. 3. To establish the factors influencing the recovery of cognitive and motor functions during ESR among children suffering severe and moderate TBI and to estimate factors’ predictive validity. The children after severe and moderate traumatic brain injury have motor (muscle tone and force, movements coordination) and cognitive (consciousness) disorders during early stage of rehabilitation resulting in hypokinesis and restricted independent activity. Individually-adjusted physical therapy during early stage of rehabilitation for patients after traumatic brain injury significantly improves their independence, though by the end of early stage of rehabilitation among severe traumatic brain injury cases the disorders of balance and walking still persist. About half of those children have motor disorders (toileting, dressing lower and upper body, bathing, independent walk, and walking stairs) and cognitive disorders (communication, social interaction, and problem solving). The motor... [to full text]