Meningeal and Visual Pathway Magnetic Resonance Imaging Analysis after Single and Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA)-Induced Disruption in Male and Female Mice

McNamara, Eileen H.; Knutsen, Andrew K.; Korotcov, Alexandru; Bosomtwi, Asamoah; Liu, Jiong; Fu, Amanda H.; Kostelnik, Claire; Grillakis, Antigone; Spencer, Haley F.; Dardzinski, Bernard J.; McCabe, Joseph T.

doi:10.1089/neu.2021.0494

Cited by 4 publications

(4 citation statements)

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“…Lyve-1 + mLV coverage/expression is decreased at 3d (mice, impact 1.9atm) [ 303 ] and 7d (rats, impact 2.6 atm) [ 304 ] after lateral fluid percussion injury (FPI). MRI of a closed-head impact model of engineered rotational acceleration (CHIMERA) shows meningeal enhancement 7d after single and repeat injury, reflecting clinical observations [ 305 ]. Controlled cortical impact (CCI) in mice presents mixed findings: Lyve-1 + morphology is increased at 7 d (impact 1.5 mm) [ 306 ], with contrasting studies showing decreases at 3 d (impact 2 mm) [ 307 ], and 1 month (impact undisclosed) [ 308 ], highlighting the nuanced and variable nature of spontaneous lymphangiogenic responses across varied mechanisms of impact and injury parameters.…”

Section: Meningeal Lymphatic Dysfunction After Tbimentioning

confidence: 89%

“…Revascularization at 3 d, 5 d,7 d. Inhibited by infection At 1 d, 3 d, 4 d and 7 d ↑ CD11b + , CD206 + myeloid cells [ 321 ] 2021 CCI (3 mm, 3 m/s, dwell time 85 ms) Male C57Bl/6J mice (9–10 wks) 1 d, 7 d, 1 year Meninges, Meningeal ILCs (Innate lymphoid cells) At 1,7d ↑ILC1-3. At 1y ↑ILC2/3 Metabolic dysregulation with ↓AMPKα1 at 1d *CCI + IL-33 (1μg) ↑pAMPKα [ 298 ] 2021 CHIMERA (single × 1 & repeat × 4) Male, Female C57Bl/6 mice (6–7 wks) 1 d, 7 d Whole brain MRI At 1d & 7d ↑ meningeal enhancement in both single and repeat impacts [ 305 ] 2022 CCI (0.5 mm or 1 mm, 5 m/s, d well undisclosed) Male C57Bl/6J mice (9–10 wks) 3 dpi, 6 wks Dura mater–RNAseq, Whole mount meninges 3dpi - ↑CD45+ myeloid (B cell) & CD11b+ cells 6 wks - ↑Ccl8, Il1β, Ccl2 Ccl7 ↑immune pathways, including interferon gamma response [ 316 ] 2022 CCI (2 mm, velocity undisclosed) Male C57Bl/6 mice (10 wks) 3 d Meningeal lymphatic endothelial cells (LECs) Flow cytometry ↓ Lyve1 LECs Microarray ↑ DEGs involved in FCERI signaling, antibody-mediated complement, Inflammatory response [ 307 ] 2022 Adapted CCI hit and run (closed head, 2 mm, 5.2 m/s, dwell time 100 ms) Male C57Bl/6J mice (8–12 wks & 20 months) 7 d, 1.5 m Whole mount meninges Meninges for bulk & scRNA-seq At 7d, ↑DEG s related to macrophages, fibroblasts, and adaptive immune cells. ↑IFNβ, IRF5, IFNAR1 At 1.5m ↑ collagen, fibroblasts ↑T/B cell DEG.…”

Section: Meningeal Lymphatic Dysfunction After Tbimentioning

confidence: 99%

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The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury

Mokbel,

Burns,

Main

2024

J Neuroinflammation

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Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer’s disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field.

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Section: Meningeal Lymphatic Dysfunction After Tbimentioning

confidence: 89%

Section: Meningeal Lymphatic Dysfunction After Tbimentioning

confidence: 99%

The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury

Mokbel,

Burns,

Main

2024

J Neuroinflammation

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show abstract

“…Immunohistochemistry was performed according to a standard protocol [ 48 , 49 ]. After being in cryoprotectant for at least a week, free-floating sections were washed three times in tris-buffered saline with 0.05% triton (TBST), processed with 0.3% hydrogen peroxide for 30 min, rewashed, and then incubated with blocking buffer (TBST with 0.2% triton, 10% goat serum (Vector Laboratories, Burlingame, CA, USA, S-1000), and 0.02% bovine serum albumin (Fisher Scientific, Waltham, MA, USA, Fraction V)) for one hour shaking at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…Images were taken on a Motic BA310 microscope (Motic, Kowloon, Hong Kong, China) with corresponding camera software at 4× magnification. To quantify regions of interest (ROIs) for Iba-1 and GFAP, the percent area stained was measured in black/white images using the Yen automatic thresholding method on Image J software (version 1.53t) [ 49 ]. Right and left values were averaged for the optic tract and the mPFC, and white and grey matter in the cerebellum were quantified separately to maintain consistent ROIs.…”

Section: Methodsmentioning

confidence: 99%

Effects of a Subanesthetic Ketamine Infusion on Inflammatory and Behavioral Outcomes after Closed Head Injury in Rats

et al. 2023

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Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine’s effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague–Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1–4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.

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Visual Impairment in Pre-Clinical Models of Mild Traumatic Brain Injury

Orbach,

Melendes,

Warren

et al. 2024

Journal of Neurotrauma

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Meningeal and Visual Pathway Magnetic Resonance Imaging Analysis after Single and Repetitive Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA)-Induced Disruption in Male and Female Mice

Cited by 4 publications

References 64 publications

The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury

The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury

Effects of a Subanesthetic Ketamine Infusion on Inflammatory and Behavioral Outcomes after Closed Head Injury in Rats

Visual Impairment in Pre-Clinical Models of Mild Traumatic Brain Injury

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