Background Traumatic brain injury (TBI) impacts 42 million people per year and is especially common among veterans and individuals experiencing homelessness. Effective treatments for TBI remain a major unmet clinical need. Enriched housing environments have been shown to ameliorate TBI symptoms, however, little to no data is available relating TBI pathology to homelessness, despite TBI being two to seven times more prevalent among those experiencing homelessness than the general population. Currently, many trials for TBI therapeutics aim to mitigate neuroinflammation. Individuals experiencing homelessness likely display greater neuroinflammation due to stresses of daily living, potentially exacerbating TBI symptoms. This unique TBI patient population must be considered to design optimal treatments for all patients. 

Methods We developed a rat model of homelessness using a novel cage switching housing environment. We rotated animals (nhomeless = 18, nstandard = 18) into dirty cages daily for 37 days, simulating housing instability and unsanitary conditions. We then induced TBI with moderate controlled cortical impact TBI surgery (nhomeless = 9, nstandard = 9). Following TBI surgery, we performed 4 days of behavioral testing including the beam walk (BW), elevated body swing test (EBST), forelimb akinesia (FA), paw grasp (PG), rotarod, and elevated-T maze. 

Results Averaged over 4 days, significant differences in motor function, demonstrated impaired function in rats with TBI compared to controls, regardless of housing (BW 85.0%, FA 104.7%, and PG 100% greater deficit in TBI). Notably, however, homelessness exacerbated the functional deficits in TBI rats (BW 93.3%, FA 40.5%, and PG 50% greater deficit). TBI rats in the homelessness model also showed a surprising recovery in functional deficits on day 4, while control housing rats continued to decline. 

Conclusion These findings exhibit the magnification of certain motor insufficiencies shortly after TBI due to homelessness, possibly due to an underlying pathophysiology. Interestingly, however, TBI rats in the homeless simulation showed more robust recovery by day 4, suggesting a form of resilience to stressful events like TBI. That exacerbation of TBI symptoms accompanies homelessness suggests that the environmental condition of the patient must be considered in disease diagnosis and to aptly treat all TBI patient populations.


Neurological Surgery - Forgotten veterans: Pathological implications of homelessness on traumatic brain injury - Neurological Surgery

Traumatic brain injury (TBI) is characterized by diffuse axonal injury that leads to neurodegeneration mediated by glial-driven neuroinflammation and neurotoxicity. Several chronic morbidities associated with TBI are psychiatric and stress-related, such as post-traumatic stress disorder. The basolateral (BLA) and central amygdala (CeA) are regulators of emotion, behavior, and autonomic function, and disruption of the amygdala due to experimental TBI has been shown to induce chronic anxiety-like behaviors, dysfunction of neurotransmission, hypertrophy of glutamatergic neurons, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Beyond their role in stress and inflammation, changes in glucocorticoid receptor (GR) expression can mediate behavior, neurotransmission, neuroplasticity, and reflect dysregulation of the HPA axis. To evaluate these processes, 64 young adult, age-matched male and naturally cycling female Sprague-Dawley underwent sham surgery or midline fluid percussion injury (mFPI), and were sacrificed at 7-, 56-, or 168-days post injury (DPI). Image processing was used to analyze ionized calcium binding adaptor molecule 1 (IBA1) and glial fibrillary acid protein (GFAP)-stained photomicrographs to quantify microglia and astrocyte activation, respectively. Visual interpretation of amino-cupric-silver (AmCuAg) staining patterns were subjectively done to assess neuropathology. Simple western blotting was performed in 58 animals (25 from histology cohort) using whole amygdala biopsies to evaluate GR protein at 7- and 56-DPI. Time post-surgery, despite sporadic sex and nuclei-specific instances, was a primary driver of microglia activation and astrogliosis by 168-DPI within the BLA/CeA. The chronic, mild increase in AmCuAg staining intensity visually observed in all groups indicated that age-related neurodegeneration was likely behind histopathologic findings. Midline FPI decreased GR protein in males only at 7-DPI. These data indicate that age and HPA axis dysregulation may be primarily responsible for previously reported behavioral, neurochemical, cellular, and molecular outcomes, ruling out TBI-induced axonal injury and chronic neurodegeneration in the BLA/CeA underlying the pathophysiology of affective-like symptoms after mFPI.

Neurological Surgery - Chronic Histopathological and Glucocorticoid Receptor Assessment of the Amygdala Post-TBI - Neurological Surgery

Making Traditional Articulation Therapy More Efficient

Background And Aims Existing research supports intensive therapy involving goal-directed training and practice of skills. Such programs are challenging to deliver in the ambulatory setting due to cost and logistics. We aimed to implement a Hand-Arm Bimanual Intensive Therapy (HABIT) program, measure and improve participant-reported outcomes, and expand program size while maintaining quality. Methods HABIT invovled a camp-like environment for 6 hours/day X 10 days, plus home programs. Fourteen campers (ages 6-11) completed the program in 3 groups. Caregiver education improvements were based on a pilot program (2017). Assisting Hand Assessment (AHA) hierarchy guided each camper's treatment (2018-2019). Program capacity increased from 4 to 6 campers. The role of psychology was was intensified yearly. Outcome assessments included AHA, Canadian Occupational Performance Measure (COPM), PROMIS Parent Proxy Upper Extremity Questionnaire, The Pediatric Outcomes Data Collection Instrument (PODCI), and participant surveys. Results: -Group AHA scores improved at program completion (P=.0006) and remained statistically significant at 30 days (P=.0007) despite a decreasing trend. Pattern consistent with literature. -8 of 13 achieved at least the smallest detectable difference (SDD), consistent with literature -Group exceeded criteria for clinically meaningful change -9 of 13 campers achieved clinically meaningful changes in performance and satisfaction -Improvements for 2018, sustained for 2019 Surveys show improved parent and patient-reported outcomes in 2018, sustained for 2019 Conclusions We implemented HABIT in our ambulatory care center with results comparable to the research literature. AHA score improvements were sustained at 30 days in an expanded program that was enhanced based on QI initiatives, with high satisfaction levels reported by participants.

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Neurological Surgery - Forgotten veterans: Pathological implications of homelessness on traumatic brain injury - Neurological Surgery

Neurological Surgery - Chronic Histopathological and Glucocorticoid Receptor Assessment of the Amygdala Post-TBI - Neurological Surgery

Making Traditional Articulation Therapy More Efficient

Intensive bimanual therapy for pediatric chronic hemiparesis: implementing research and optimizing caregiver and patient-reported outcomes

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