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An Understated Comorbidity: The Impact of Homelessness on Traumatic Brain Injury

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Neurotherapeutics

Abstract

Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a significant overlap in the veteran and homeless population, possibly accounting for the two to seven times greater incidence of TBI among those experiencing HL than the general population. Despite these statistics, individuals experiencing HL are often underdiagnosed and ineffectively treated for TBI. We introduced a novel model of HL. Over 5 weeks, adult Sprague–Dawley rats were randomly assigned to one of the following conditions: TBI only, HL only, TBI + HL, or control (n = 9 per group). To emulate HL, animals (2 animals per cage) were exposed to soiled beddings for 5 weeks. Subsequently, animals were introduced to TBI by using the moderate controlled cortical impact model, then underwent 4 consecutive days of behavioral testing (beam walk (BW), elevated body swing test (EBST), forelimb akinesia (FA), paw grasp (PG), Rotorod, and elevated T-maze). Nissl staining was performed to determine the peri-impact cell survival and the integrity of corpus callosum area. Motor function was significantly impaired by TBI, regardless of housing (beam walk or BW 85.0%, forelimb akinesia or FA 104.7%, and paw grasp or PG 100% greater deficit compared to control). Deficits were worsened by HL in TBI rats (BW 93.3%, FA 40.5%, and PG 50% greater deficit). Two-way ANOVA revealed BW (F(4, 160) = 31.69, p < 0.0001), FA (F(4, 160) = 13.71, p < 0.0001), PG (F(4, 160) = 3.873, p = 0.005), Rotorod (F(4, 160), p = 1.116), and EBST (F(4, 160) = 6.929, p < 0.0001) showed significant differences between groups. The Rotorod and EBST tests showed TBI-induced functional deficits when analyzed by day, but these deficits were not exacerbated by HL. TBI only and TBI + HL rats exhibited typical cortical impact damage (F(3,95) = 51.75, p < 0.0001) and peri-impact cell loss compared to control group (F(3,238) = 47.34, p < 0.0001). Most notably, TBI + HL rats showed significant alterations in WM area measured via the corpus callosum (F(3, 95) = 3.764, p = 0.0133). Worsened behavioral outcomes displayed by TBI + HL rats compared to TBI alone suggest HL contributes to TBI functional deficits. While an intact white matter, such as the corpus callosum, may lessen the consequent functional deficits associated with TBI by enhancing hemispheric communications, there are likely alternative cellular and molecular pathways mitigating TBI-associated inflammatory or oxidative stress responses. Here, we showed that the environmental condition of the patient, i.e., HL, participates in white matter integrity and behavioral outcomes, suggesting its key role in the disease diagnosis to aptly treat TBI patients.

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Data Availability

All research data are available from Cesar V. Borlongan upon reasonable request.

Abbreviations

TBI:

Traumatic brain injury

HL:

Homelessness

CC:

Corpus callosum

WM:

White matter

GM:

Gray matter

BW:

Beam walk

EBST:

Elevated body swing test

FA:

Forelimb akinesia

PG:

Paw grasp

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Authors and Affiliations

  1. University of South Florida Morsani College of Medicine, 560 Channelside Dr., Tampa, FL, 33606, USA

    M. Monsour

  2. Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B Downs Blvd, Tampa, FL, 33612, USA

    J.-Y. Lee & C.V. Borlongan

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The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: C.V.B. holds leadership position with University of South Florida, a patent holder, and has patent applications on stem cell biology and its therapeutic applications, consultant to a number of stem cell–based companies, and research funding from the NIH. All the other authors declared no potential conflicts of interest.

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Monsour, M., Lee, JY. & Borlongan, C. An Understated Comorbidity: The Impact of Homelessness on Traumatic Brain Injury. Neurotherapeutics 20, 1446–1456 (2023). https://doi.org/10.1007/s13311-023-01419-8

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