MCC950 Attenuates Microglial NLRP3-Mediated Chronic Neuroinflammation and Memory Impairment in a Rat Model of Repeated Low-Level Blast Exposure.

Blast-induced traumatic brain injury is typically regarded as a signature medical concern for military personnel who are exposed to explosive devices in active combat zones. However, soldiers as well as law enforcement personnel may be repeatedly exposed to low-level blasts during training sessions with heavy weaponries as part of combat readiness. Service personnel who sustain neurotrauma from repeated low-level blast (rLLB) exposure do not display overt pathological symptoms immediately but rather develop mild symptoms including cognitive impairments, attention deficits, mood changes, irritability, and sleep disturbances over time.

Temporal Changes in Functional and Structural Neuronal Activities in Auditory System in Non-Severe Blast-Induced Tinnitus.

: Epidemiological data indicate that blast exposure is the most common morbidity responsible for mild TBI among Service Members (SMs) during recent military operations. Blast-induced tinnitus is a comorbidity frequently reported by veterans, and despite its wide prevalence, it is also one of the least understood. Tinnitus arising from blast exposure is usually associated with direct structural damage that results in a conductive and sensorineural impairment in the auditory system.

Insilico Screening of Pentacyclic Triterpenoids against Vascular Dementia Target's.

Vascular dementia (VaD) accounts to 30% of cases and is predicted as second most common form of dementia after Alzheimer's disease by WHO. Earlier studies reported that plant-derived pentacyclic triterpenoids possess a wide range of pharmacological activities but these compounds are not extensively studied for their neuroprotective potential against VaD. This in silico approach was designed to screen 20 pentacyclic triterpenoid plant compounds against known targets of VaD using Flare software.

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

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.

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

Blast injuries are common among the military service members and veterans. One of the devastating effects of blast wave induced TBI is either temporary or permanent hearing loss. Treating hearing loss using minocycline is restricted by optimal drug concentration, route of administration, and its half-life.

Hemolytic iron regulation in traumatic brain injury and alcohol use.

Hemorrhage is a major component of traumatic brain injury (TBI). Red blood cells, accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion and release free iron into the central nervous system. This iron must be managed to prevent iron neurotoxicity and ferroptosis.

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

Blast-induced neurotrauma (BINT) is not only a signature injury to soldiers in combat field and training facilities but may also a growing concern in civilian population due to recent increases in the use of improvised explosives by insurgent groups. Unlike moderate or severe BINT, repeated low-level blast (rLLB) is different in its etiology as well as pathology. Due to the constant use of heavy weaponry as part of combat readiness, rLLB usually occurs in service members undergoing training as part of combat readiness.

Fisetin, potential flavonoid with multifarious targets for treating neurological disorders: An updated review.

Neurodegenerative disorders pose a significant health burden and imprint a debilitative impact on the quality of life. Importantly, aging is intricately intertwined with the progression of these disorders, and their prevalence increases with a rise in the aging population worldwide. In recent times, fisetin emerged as one of the potential miracle molecules to address neurobehavioral and cognitive abnormalities.

Behavioral Deficits in Animal Models of Blast Traumatic Brain Injury.

Blast exposure has been identified to be the most common cause for traumatic brain injury (TBI) in soldiers. Over the years, rodent models to mimic blast exposures and the behavioral outcomes observed in veterans have been developed extensively. However, blast tube design and varying experimental parameters lead to inconsistencies in the behavioral outcomes reported across research laboratories.

Ocimum Sanctum Linn: A Potential Adjunct Therapy for Hyperhomocysteinemia-Induced Vascular Dementia.

Vascular dementia (VaD) is well recognized as the second most familiar form of dementia in the aged population. The present study is aimed to investigate the neuroprotective effects of ethanolic extract of leaves of Ocimum sanctum (EEOS) against hyperhomocysteinemia (HHcy)-induced vascular dementia (VaD) in Wistar rats. HHcy was induced by administering L-methionine (1.

Synergistic Role of Oxidative Stress and Blood-Brain Barrier Permeability as Injury Mechanisms in the Acute Pathophysiology of Blast-induced Neurotrauma.

Blast-induced traumatic brain injury (bTBI) has been recognized as the common mode of neurotrauma amongst military and civilian personnel due to an increased insurgent activity domestically and abroad. Previous studies from our laboratory have identified enhanced blood-brain barrier (BBB) permeability as a significant, sub-acute (four hours post-blast) pathological change in bTBI. We also found that NADPH oxidase (NOX)-mediated oxidative stress occurs at the same time post-blast when the BBB permeability changes.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.

Highly sensitive LC-MS/MS-ESI method for determination of phenelzine in human plasma and its application to a human pharmacokinetic study.

A selective, sensitive and rapid LC-MS/MS method has been developed and validated for quantification of the phenelzine (PZ) in 200μL of human plasma using hydroxyzine (HZ) as an internal standard (IS) as per regulatory guidelines. The sample preparation involved the derivatization of PZ using pentaflurobenzaldehyde followed by solid phase extraction process to extract PZ and HZ from human plasma. LC-MS/MS was operated under the multiple reaction-monitoring mode (MRM) using the electro spray ionization technique in positive ion mode and the transitions of m/z 305.