Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes

Ravula, Arun Reddy; Rodríguez, José Manuel Pestano; Younger, Daniel; Perumal, Venkatesan; Shao, Ningning; Rao, Kakulavarapu V. Rama; Pfister, Bryan J.; Chandra, Namas

doi:10.1016/j.expneurol.2021.113938

Cited by 20 publications

(13 citation statements)

References 48 publications

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“…AlexaFluor 488(green) were used for NeuN and IBA1. Anti-fading reagent with DAPI (ProLong™ Gold Antifade Mountant with DAPI, Invitrogen) was used before putting cover slide ( Kuriakose et al., 2019 ; Murugan et al., 2020 ; Rana et al., 2020 ; Ravula et al., 2022b ). Subsequent immunostaining, followed Fluorescence intensities analysis as described in our previous study ( Sundaramurthy et al., 2012 ; Younger et al., 2019 ; Kuriakose et al., 2018 ; Chandra et al., 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Perumal¹,

Ravula²,

Shao³

et al. 2023

Journal of Otology

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Section: Methodsmentioning

confidence: 99%

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Perumal¹,

Ravula²,

Shao³

et al. 2023

Journal of Otology

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“…Blast TBI rats were injected with fluorescently labeled targeted and non-targeted nanoparticles by tail vein. After 4 h, the brain was harvested and fixed with 4% paraformaldehyde for 24 h, incubated in a 30% sucrose solution for 72 h, and then stored at 80 °C until sectioning [ 80 , 81 , 82 ]. After blocking with 10% donkey serum for 1 h at room temperature, sections were incubated with microglia/macrophages (goat anti-Iba1, Invitrogen, 1:250 overnight at 4 °C), astrocytes (mouse anti-GFAP, Thermo Fischer Scientific, 1:400, overnight at 4 °C Primary antibodies were detected using donkey anti-goat and anti-mouse Alexa Fluor ® 488 (Invitogen, 1:1000, 1 h at RT).…”

Section: Methodsmentioning

confidence: 99%

“…The total time spent exploring objects was recorded using ANY-Maze software (version 7.1, Stoelting, Wood Dale, IL, USA). A preference index [ 82 ] for the novel object was calculated as

…”

Section: Methodsmentioning

confidence: 99%

Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model

et al. 2023

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Traumatic brain injury (TBI) is a major source of death and disability worldwide as a result of motor vehicle accidents, falls, attacks and bomb explosions. Currently, there are no FDA-approved drugs to treat TBI patients predominantly because of a lack of appropriate methods to deliver drugs to the brain for therapeutic effect. Existing clinical and pre-clinical studies have shown that minocycline’s neuroprotective effects either through high plasma protein binding or an increased dosage requirement have resulted in neurotoxicity. In this study, we focus on the formulation, characterization, in vivo biodistribution, behavioral improvements, neuroprotective effect and toxicity of transferrin receptor-targeted (tf) conjugated minocycline loaded albumin nanoparticles in a blast-induced TBI model. A novel tf conjugated minocycline encapsulated albumin nanoparticle was developed, characterized and quantified using a validated HPLC method as well as other various analytical methods. The results of the nanoformulation showed small, narrow hydrodynamic size distributions, with high entrapment, loading efficiencies and sustained release profiles. Furthermore, the nanoparticle administered at minimal doses in a rat model of blast TBI was able to cross the blood–brain barrier, enhanced nanoparticle accumulation in the brain, improved behavioral outcomes, neuroprotection, and reduced toxicity compared to free minocycline. Hence, tf conjugated minocycline loaded nanoparticle elicits a neuroprotective effect and can thus offer a potential therapeutic effect.

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“…Blast injury: The rats were subjected to a single blast wave at the Center of Injury Biomechanics, Materials, and Medicine (New Jersey Institute of Technology, Newark, NJ, USA) in a 9 inch square cross-section shock tube, as described previously [43][44][45][46]. The principal animals used in this study were rats, with 4-5 animal in each experimental group (power value of 0.8, α = 0.05) based on a power analysis.…”

Section: Transwell Migration Assaymentioning

confidence: 99%

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

Perumal

Ravula

Agas

et al. 2023

Micro

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide, affecting over 10 million people annually, with an estimated cost of $76.5 billion. Although apocynin freely transverses the blood–brain barrier (BBB), its application is limited due to its rapid elimination, low terminal half-life (t1/2 = 6.7 min), narrow dose–response relationship, and cytotoxicity, thereby requiring repeated dosages. With this study, we aimed to develop transferrin-functionalized nanoparticles encapsulating apocynin to treat neuroinflammation for targeted drug delivery to sites of brain injury. As a preliminary approach, we endeavored to optimize the formulation parameters of apocynin-loaded albumin nanoparticles prepared through the desolvation method. The nanoparticles were characterized for their size, polydispersity, surface charge, drug loading and in vitro drug release. In this study, we also investigated the anti-inflammatory and neuroprotective effects of free apocynin and nanoparticle-loaded apocynin in neuronal cells. We show that the developed formulation displayed monodispersed, nanosized particles with higher entrapment efficiency, loading, stability, and sustained release profiles. The permeability of the nanoparticles across HBMECs reached the maximum at 67%. The in vivo evaluation revealed the enhanced uptake of transferrin-anchored nanoparticles in the brain tissues when compared with unmodified nanoparticles after I.V. administration. In vivo nanoparticle localization studies using a blast TBI (bTBI) model and confocal fluorescence microscopy have shown that tf-apoANPs are successful in delivering relatively high amounts of nanoparticles to the brain parenchyma and glial cells compared to non-targeted nanoparticles. We also establish that targeted nanoparticles accumulate in the brain. In conclusion, tf-apoANPs are efficacious carriers for targeted delivery across the blood–brain barrier to potentially treat neuroinflammation in brain injury and other diseases.

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Animal model of repeated low-level blast traumatic brain injury displays acute and chronic neurobehavioral and neuropathological changes

Cited by 20 publications

References 48 publications

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Effect of minocycline and its nano-formulation on central auditory system in blast-induced hearing loss rat model

Enhanced Targeted Delivery of Minocycline via Transferrin Conjugated Albumin Nanoparticle Improves Neuroprotection in a Blast Traumatic Brain Injury Model

Transferrin-Grafted Albumin Nanoparticles for the Targeted Delivery of Apocynin and Neuroprotection in an In Vitro Model of the BBB

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