Behavioral Deficits in Animal Models of Blast Traumatic Brain Injury

Aravind, Aswati; Ravula, Arun Reddy; Chandra, Namas; Pfister, Bryan J.

doi:10.3389/fneur.2020.00990

Cited by 36 publications

(25 citation statements)

References 134 publications

(183 reference statements)

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“…The early recovery in foot-faults (3 dpi) is potentially due to abatement of the initial insult of tissue edema, which follows a similar time course [ 45 ]. Many studies of cortical brain injury, such as stroke and TBI, have reported early recovery of deficits and been extensively reviewed [ 46 , 47 ]. In a model of stroke, behavioral recovery corresponded strongly with blood flow adjacent to the injury site and related to vessel density [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal dynamics of microvascular recovery after acquired cortical injury

Lin

Chen

Jullienne

et al. 2022

acta neuropathol commun

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Acquired brain injuries due to trauma damage the cortical vasculature, which in turn impairs blood flow to injured tissues. There are reports of vascular morphological recovery following traumatic brain injury, but the remodeling process has not been examined longitudinally in detail after injury in vivo. Understanding the dynamic processes that influence recovery is thus critically important. We evaluated the longitudinal and dynamic microvascular recovery and remodeling up to 2 months post injury using live brain miniscope and 2-photon microscopic imaging. The new imaging approaches captured dynamic morphological and functional recovery processes at high spatial and temporal resolution in vivo. Vessel painting documented the initial loss and subsequent temporal morphological vascular recovery at the injury site. Miniscopes were used to longitudinally image the temporal dynamics of vascular repair in vivo after brain injury in individual mice across each cohort. We observe near-immediate nascent growth of new vessels in and adjacent to the injury site that peaks between 14 and 21 days post injury. 2-photon microscopy confirms new vascular growth and further demonstrates differences between cortical layers after cortical injury: large vessels persist in deeper cortical layers (> 200 μm), while superficial layers exhibit a dense plexus of fine (and often non-perfused) vessels displaying regrowth. Functionally, blood flow increases mirror increasing vascular density. Filopodia development and endothelial sprouting is measurable within 3 days post injury that rapidly transforms regions devoid of vessels to dense vascular plexus in which new vessels become increasingly perfused. Within 7 days post injury, blood flow is observed in these nascent vessels. Behavioral analysis reveals improved vascular modulation after 9 days post injury, consistent with vascular regrowth. We conclude that morphological recovery events are closely linked to functional recovery of blood flow to the compromised tissues, which subsequently leads to improved behavioral outcomes.

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Section: Discussionmentioning

confidence: 99%

Longitudinal dynamics of microvascular recovery after acquired cortical injury

Lin

Chen

Jullienne

et al. 2022

acta neuropathol commun

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“… 28 In a clinical study, 50% of veterans exposed to bTBI experienced anxiety disorders. 29 , 30 Anxiety disorders in animal models were characterized by increased arousal, expectancy, autonomic and neuroendocrine activation, as well as a transition from ongoing behaviors to an escape or other defensive behaviors. 31 Anxiety-like behaviors have been reported 3 months after repetitive, but not single, impact acceleration-induced mTBI in rats.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Low-Intensity Blast Non-Inertial Brain Injury on Anxiety-Like Behaviors in Mice: Home-Cage Monitoring Assessments

Siedhoff

Chen

Balderrama

et al. 2022

Neurotrauma Reports

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Mild traumatic brain injury induced by low-intensity blast (LIB) exposure poses concerns in military personnel. Using an open-field, non-inertial blast model and assessments by conventional behavioral tests, our previous studies revealed early-phase anxiety-like behaviors in LIB-exposed mice. However, the impact of LIB upon long-term anxiety-like behaviors requires clarification. This study applied a highly sensitive automated home-cage monitoring (HCM) system, which minimized human intervention and environmental changes, to assess anxiety-like responses in mice 3 months after LIB exposure. Initial assessment of 72-h spontaneous activities in a natural cage condition over multiple light and dark phases showed altered sheltering behaviors. LIB-exposed mice exhibited a subtle, but significantly decreased, duration of short shelter visits as compared to sham controls. Other measured responses between LIB-exposed mice and sham controls were insignificant. When behavioral assessments were performed in a challenged condition using an aversive spotlight, LIB-exposed mice demonstrated a significantly higher frequency of movements of shorter distance and duration per movement. Taken together, these findings demonstrated the presence of chronic anxiety-like behaviors assessed by the HCM system under both natural and challenged conditions in mice occurring post-LIB exposure. This model thus provides a platform to test for screening and interventions on anxiety disorders occurring after LIB non-inertial brain injury.

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“…Experimental models of TBI have been developed with the goal of investigating the mechanisms of primary and secondary injury sequelae (Tables 1 and 2 and refs. [22][23][24][25][26][27].…”

Section: Tbi Pathophysiology and Long-term Consequencesmentioning

confidence: 99%