ICAM-1 Deletion Using CRISPR/Cas9 Protects the Brain from Traumatic Brain Injury-Induced Inflammatory Leukocyte Adhesion and Transmigration Cascades by Attenuating the Paxillin/FAK-Dependent Rho GTPase Pathway.

Intercellular adhesion molecule-1 (ICAM-1) is identified as an initiator of neuroinflammatory responses that lead to neurodegeneration and cognitive and sensory-motor deficits in several pathophysiological conditions including traumatic brain injury (TBI). However, the underlying mechanisms of ICAM-1-mediated leukocyte adhesion and transmigration and its link with neuroinflammation and functional deficits following TBI remain elusive. Here, we hypothesize that blocking of ICAM-1 attenuates the transmigration of leukocytes to the brain and promotes functional recovery after TBI.

Nrf2 as a Potential Therapeutic Target for Traumatic Brain Injury.

In this review, we discuss the possibility and feasibility of nuclear factor erythroid 2-related factor 2 (Nrf2) as a therapeutic target to minimize the devastating effects of a brain injury. To complete this review, comprehensive literature searches were conducted in MEDLINE, PubMed, Embase, and PsycINFO databases for English scientific peer-reviewed articles through December 2022. This short review addressed the different sources of oxidative stress and its effects on blood-brain barrier (BBB) dysfunction, mitochondrial damage, and changes in a variety of inflammatory molecules associated with central nervous system (CNS) injury.

Discovery of novel microRNAs and their pathogenic responsive target genes in mild traumatic brain injury.

MicroRNAs (miRNAs) are non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. They are profound mediators of molecular and cellular changes in several pathophysiological conditions. Since miRNAs play major roles in regulating gene expression after traumatic brain injury (TBI), their possible role in diagnosis, prognosis, and therapy is not much explored.

Synergistic effect of mild traumatic brain injury and alcohol aggravates neuroinflammation, amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations: Impact on psychological stress.

After a mild traumatic brain injury (mTBI), victims often experience emotional/psychological stress such as heightened irritability, anxiety, apathy, and depression. Severe mental health complications are common in military populations following a combat-acquired TBI and intensified unhealthy alcohol use. The high prevalence of alcohol abuse among TBI victims underscores how alcohol abuse exacerbates emotional/psychological symptoms such as depression and anxiety.

NADPH oxidase-induced activation of transforming growth factor-beta-1 causes neuropathy by suppressing antioxidant signaling pathways in alcohol use disorder.

Oxidative signaling and inflammatory cascades are the central mechanism in alcohol-induced brain injury, which result in glial activation, neuronal and myelin loss, neuronal apoptosis, and ultimately long-term neurological deficits. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 in alcohol use disorder (AUD)-induced brain damage is unknown. In this study, our objective is to study ethanol-induced activation of TGF-β1 and associated mechanisms of neuroinflammation and apoptosis.

Intercellular Adhesion Molecule-1-Induced Posttraumatic Brain Injury Neuropathology in the Prefrontal Cortex and Hippocampus Leads to Sensorimotor Function Deficits and Psychological Stress.

Intercellular adhesion molecule-1 (ICAM-1) promotes adhesion and transmigration of circulating leukocytes across the blood-brain barrier (BBB). Traumatic brain injury (TBI) causes transmigrated immunocompetent cells to release mediators [function-associated antigen (LFA)-1 and macrophage-1 antigen (Mac-1)] that stimulate glial and endothelial cells to express ICAM-1 and release cytokines, sustaining neuroinflammation and neurodegeneration. Although a strong correlation exists between TBI-mediated inflammation and impairment in functional outcome following brain trauma, the role of ICAM-1 in impairing functional outcome by inducing neuroinflammation and neurodegeneration after TBI remains inconclusive.

PTEN Blocking Stimulates Corticospinal and Raphespinal Axonal Regeneration and Promotes Functional Recovery After Spinal Cord Injury.

The long-term disabilities associated with spinal cord injury (SCI) are primarily due to the absence of robust neuronal regeneration and functional plasticity. The inability of the axon to regenerate after SCI is contributed by several intrinsic factors that trigger a cascade of molecular growth program and modulates axonal sprouting. Phosphatase and tensin homolog (PTEN) is one of the intrinsic factors contributing to growth failure after SCI, however, the underlying mechanism is not well known.

Traumatic brain injury-induced downregulation of Nrf2 activates inflammatory response and apoptotic cell death.

Recent studies from our group and others have demonstrated that oxidative stress, Ca signaling, and neuroinflammation are major mechanisms contributing to post-traumatic neurodegeneration. The present study investigated the mechanisms of regulation of nuclear factor E2-related factor 2 (Nrf2) and its role in regulating antioxidant genes and oxidative stress-induced neuroinflammation and neurodegeneration following TBI. Nrf2 transcriptional system is the major regulator of endogenous defense mechanisms operating within the cells.

A Novel Design of an Intelligent Drug Delivery System Based on Nanoantenna Particles.

Compound nanoparticle drug delivery system plays an important role in the interaction with lymph nodes. There are three primary types of lymphocytes: B cells, T cells, and natural killer cells. When the cells of the immune system turn carcinogenic, they assault body cells.

Impairment of pericyte-endothelium crosstalk leads to blood-brain barrier dysfunction following traumatic brain injury.

The blood-brain barrier (BBB) constitutes a neurovascular unit formed by microvascular endothelial cells, pericytes, and astrocytes. Brain pericytes are important regulators of BBB integrity, permeability, and blood flow. Pericyte loss has been implicated in injury; however, how the crosstalk among pericytes, endothelial cells, and astrocytes ultimately leads to BBB dysfunction in traumatic brain injury (TBI) remains elusive.

Synergistic Inhibition of ERK1/2 and JNK, Not p38, Phosphorylation Ameliorates Neuronal Damages After Traumatic Brain Injury.

Mitogen-activated protein (MAP) kinases are serine/threonine protein kinases that play a critical role in signal transduction and are activated by phosphorylation in response to a variety of pathophysiology stimuli. While MAP kinase signaling has a significant role in the pathophysiology of several neurodegenerative diseases, the precise function of activation of MAP kinase in traumatic brain injury (TBI) is unknown. Therefore, it is important to study the role of MAP kinase signaling in TBI-associated neurological ailments.

Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI).

Impairment of Thiamine Transport at the GUT-BBB-AXIS Contributes to Wernicke's Encephalopathy.

Wernicke's encephalopathy, a common neurological disease, is caused by thiamine (vitamin B1) deficiency. Neuropathy resulting from thiamine deficiency is a hallmark of Wernicke-Korsakoff syndrome in chronic alcohol users. The underlying mechanisms of this deficiency and progression of neuropathy remain to be understood.

Angiotensin II Causes Neuronal Damage in Stretch-Injured Neurons: Protective Effects of Losartan, an Angiotensin T Receptor Blocker.

Angiotensin II (Ang II) is a mediator of oxidative stress via activation/induction of reactive oxygen and nitrogen species-generating enzymes, NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS). We investigated the hypothesis that overproduction of Ang II during traumatic brain injury (TBI) induces the activation of the oxidative stress, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury. We first established that stretch injury causes a rapid increase in the level of Ang II, which causes the release of pro-inflammatory cytokines, IL-1β and TNF-α, via the induction of oxidative stress.

Transforming growth factor-beta 1 signaling regulates neuroinflammation and apoptosis in mild traumatic brain injury.

Mild traumatic brain injury (mTBI) is a low-level injury, which often remains undiagnosed, and in most cases it leads to death and disability as it advances as secondary injury. Therefore, it is important to study the underlying signaling mechanisms of mTBI-associated neurological ailments. While transforming growth factor-beta1 (TGF-β1) has a significant role in inflammation and apoptosis in myriads of other pathophysiological conditions, the precise function of increased TGF-β1 after mTBI is unknown.

Activation of NLRP3 inflammasome by cholesterol crystals in alcohol consumption induces atherosclerotic lesions.

Epidemiological studies showed a strong association between alcoholism and incidence of stroke, for which the underlying causative mechanisms remain to be understood. Here we found that infiltration of immune cells and deposition of cholesterol at the site of brain artery/capillary injury induced atherosclerosis in chronic alcohol (ethanol) consumption in the presence or absence of high-fat diet. Conversion of cholesterol into sharp edges of cholesterol crystals (CCs) in alcohol intake was key to activation of NLRP3 inflammasome, induction of cerebral atherosclerosis, and development of neuropathy around the atherosclerotic lesions.

Two PTP receptors mediate CSPG inhibition by convergent and divergent signaling pathways in neurons.

Receptor protein tyrosine phosphatase σ (PTPσ) and its subfamily member LAR act as transmembrane receptors that mediate growth inhibition of chondroitin sulfate proteoglycans (CSPGs). Inhibition of either receptor increases axon growth into and beyond scar tissues after CNS injury. However, it is unclear why neurons express two similar CSPG receptors, nor whether they use the same or different intracellular pathways.

Role of Matrix Metalloproteinases in the Pathogenesis of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Studies revealed that the pathogenesis of TBI involves upregulation of MMPs. MMPs form a large family of closely related zinc-dependent endopeptidases, which are primarily responsible for the dynamic remodulation of the extracellular matrix (ECM).

Traumatic brain injury induced matrix metalloproteinase2 cleaves CXCL12α (stromal cell derived factor 1α) and causes neurodegeneration.

Traumatic brain injury (TBI), even at mild levels, can activate matrix metalloproteinases (MMPs) and the induction of neuroinflammation that can result in blood brain barrier breakdown and neurodegeneration. MMP2 has a significant role in neuroinflammation and neurodegeneration by modulating the chemokine CXCL12α (stromal cell derived factor SDF-1α) signaling pathway and the induction of apoptosis. SDF-1α is responsible for cell proliferation and differentiation throughout the nervous system and is also implicated in various neurodegenerative illnesses.

High Ca Influx During Traumatic Brain Injury Leads to Caspase-1-Dependent Neuroinflammation and Cell Death.

We investigated the hypothesis that high Ca influx during traumatic brain injury induces the activation of the caspase-1 enzyme, which triggers neuroinflammation and cell apoptosis in a cell culture model of neuronal stretch injury and an in vivo model of fluid percussion injury (FPI). We first established that stretch injury causes a rapid increase in the intracellular Ca level, which activates interleukin-converting enzyme caspase-1. The increase in the intracellular Ca level and subsequent caspase-1 activation culminates into neuroinflammation via the maturation of IL-1β.

Neurons can be labeled with unique hues by helper virus-free HSV-1 vectors expressing Brainbow.

Background: A central problem in neuroscience is elucidating synaptic connections, the connectome. Because mammalian forebrains contain many neurons, labeling specific neurons with unique tags is desirable. A novel technology, Brainbow, creates hundreds of hues by combinatorial expression of multiple fluorescent proteins (FPs).

Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death in the young age group and leads to persisting neurological impairment in many of its victims. It may result in permanent functional deficits because of both primary and secondary damages. This review addresses the role of oxidative stress in TBI-mediated secondary damages by affecting the function of the vascular unit, changes in blood-brain barrier (BBB) permeability, posttraumatic edema formation, and modulation of various pathophysiological factors such as inflammatory factors and enzymes associated with trauma.

Application of microsatellite markers in conservation genetics and fisheries management: recent advances in population structure analysis and conservation strategies.

Microsatellites are the most popular and versatile genetic marker with myriads of applications in population genetics, conservation biology, and evolutionary biology. These are the arrays of DNA sequences, consisting of tandemly repeating mono-, di-, tri-, and tetranucleotide units, which are distributed throughout the genomes of most eukaryotic species. Microsatellites are codominant in nature, highly polymorphic, easily typed, and Mendelian inherited, all properties which make them very suitable for the study of population structure and pedigree analysis and capable of detecting differences among closely related species.

Crisscross heart with dextrocardia and intact interventricular septum.

Crisscross heart is a rare congenital heart disease characterized by a twisted atrioventricular connection, as a result of rotation of the ventricular mass along its long axis. We report an asymptomatic 48-year-old woman referred to us for evaluation of a cardiac murmur. Further evaluation showed situs solitus, dextrocardia with normal atrioventricular and ventriculoarterial connection, and a crisscross relation of the atrioventricular valves.