The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and improves neuropathology following controlled cortical impact in male rats.

Traumatic brain injury (TBI) is a leading cause of human death and disability with no effective therapy to fully prevent long-term neurological deficits in surviving patients. Ketone ester supplementation is protective in animal models of neurodegeneration, but its efficacy against TBI pathophysiology is unknown. Here, we assessed the neuroprotective effect of the ketone monoester, 3-hydroxybutyl-3-hydroxybutyrate, (KE) in male Sprague Dawley rats (=32).

The Recovery of GABAergic Function in the Hippocampus CA1 Region After mTBI.

Traumatic brain injury (TBI) is a major public health concern in the USA. There are approximately 2.5 million brain injuries annually, 90% of which may be classified as mild since these individuals do not display clear morphological abnormalities following injury on imaging.

Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats.

Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability.

Control diet in a high-fat diet study in mice: Regular chow and purified low-fat diet have similar effects on phenotypic, metabolic, and behavioral outcomes.

Background: Differences in the composition of control diets may confound outcomes in studies investigating dietary effects.

Objective: We compared the effects of two control diets commonly used in mice studies, chow (SD) and a purified low-fat diet (LFD), in relation to a chronic high-fat diet (HFD). We hypothesized that SD and LFD will have similar effects on phenotypic, metabolic, and behavioral outcomes.

Behavioral changes in male mice fed a high-fat diet are associated with IL-1β expression in specific brain regions.

High-fat diet (HFD)-induced obesity is associated with not only increased risk of metabolic and cardiovascular diseases, but cognitive deficit, depression and anxiety disorders. Obesity also leads to low-grade peripheral inflammation, which plays a major role in the development of metabolic alterations. Previous studies suggest that obesity-associated central inflammation may underlie the development of neuropsychiatric deficits, but further research is needed to clarify this relationship.

Acute Response of the Hippocampal Transcriptome Following Mild Traumatic Brain Injury After Controlled Cortical Impact in the Rat.

We have previously demonstrated that mild controlled cortical impact (mCCI) injury to rat cortex causes indirect, concussive injury to underlying hippocampus and other brain regions, providing a reproducible model for mild traumatic brain injury (mTBI) and its neurochemical, synaptic, and behavioral sequelae. Here, we extend a preliminary gene expression study of the hippocampus-specific events occurring after mCCI and identify 193 transcripts significantly upregulated, and 21 transcripts significantly downregulated, 24 h after mCCI. Fifty-three percent of genes altered by mCCI within 24 h of injury are predicted to be expressed only in the non-neuronal/glial cellular compartment, with only 13% predicted to be expressed only in neurons.

GABAergic interneuronal loss and reduced inhibitory synaptic transmission in the hippocampal CA1 region after mild traumatic brain injury.

Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region.

A rat model of nerve agent exposure applicable to the pediatric population: The anticonvulsant efficacies of atropine and GluK1 antagonists.

Inhibition of acetylcholinesterase (AChE) after nerve agent exposure induces status epilepticus (SE), which causes brain damage or death. The development of countermeasures appropriate for the pediatric population requires testing of anticonvulsant treatments in immature animals. In the present study, exposure of 21-day-old (P21) rats to different doses of soman, followed by probit analysis, produced an LD50 of 62μg/kg.

Reduced GABAergic inhibition in the basolateral amygdala and the development of anxiety-like behaviors after mild traumatic brain injury.

Traumatic brain injury (TBI) is a major public health concern affecting a large number of athletes and military personnel. Individuals suffering from a TBI risk developing anxiety disorders, yet the pathophysiological alterations that result in the development of anxiety disorders have not yet been identified. One region often damaged by a TBI is the basolateral amygdala (BLA); hyperactivity within the BLA is associated with increased expression of anxiety and fear, yet the functional alterations that lead to BLA hyperexcitability after TBI have not been identified.

ASIC1a activation enhances inhibition in the basolateral amygdala and reduces anxiety.

The discovery that even small changes in extracellular acidity can alter the excitability of neuronal networks via activation of acid-sensing ion channels (ASICs) could have therapeutic application in a host of neurological and psychiatric illnesses. Recent evidence suggests that activation of ASIC1a, a subtype of ASICs that is widely distributed in the brain, is necessary for the expression of fear and anxiety. Antagonists of ASIC1a, therefore, have been proposed as a potential treatment for anxiety.

The recovery of acetylcholinesterase activity and the progression of neuropathological and pathophysiological alterations in the rat basolateral amygdala after soman-induced status epilepticus: relation to anxiety-like behavior.

Organophosphorus nerve agents are powerful neurotoxins that irreversibly inhibit acetylcholinesterase (AChE) activity. One of the consequences of AChE inhibition is the generation of seizures and status epilepticus (SE), which cause brain damage, resulting in long-term neurological and behavioral deficits. Increased anxiety is the most common behavioral abnormality after nerve agent exposure.

Temporal course of changes in gene expression suggests a cytokine-related mechanism for long-term hippocampal alteration after controlled cortical impact.

Mild traumatic brain injury (mTBI) often has long-term effects on cognitive function and social behavior. Altered gene expression may be predictive of long-term psychological effects of mTBI, even when acute clinical effects are minimal or transient. Controlled cortical impact (CCI), which causes concussive, but nonpenetrant, trauma to underlying (non-cortical) brain, resulting in persistent changes in hippocampal synaptic function, was used as a model of mTBI.

Acetylcholinesterase inhibition in the basolateral amygdala plays a key role in the induction of status epilepticus after soman exposure.

Exposure to nerve agents induces intense seizures (status epilepticus, SE), which cause brain damage or death. Identification of the brain regions that are critical for seizure initiation after nerve agent exposure, along with knowledge of the physiology of these regions, can facilitate the development of pretreatments and treatments that will successfully prevent or limit the development of seizures and brain damage. It is well-established that seizure initiation is due to excessive cholinergic activity triggered by the nerve agent-induced irreversible inhibition of acetylcholinesterase (AChE).

Presynaptic facilitation of glutamate release in the basolateral amygdala: a mechanism for the anxiogenic and seizurogenic function of GluK1 receptors.

Kainate receptors containing the GluK1 subunit (GluK1Rs; previously known as GluR5 kainate receptors) are concentrated in certain brain regions, where they play a prominent role in the regulation of neuronal excitability, by modulating GABAergic and/or glutamatergic synaptic transmission. In the basolateral nucleus of the amygdala (BLA), which plays a central role in anxiety as well as in seizure generation, GluK1Rs modulate GABAergic inhibition via postsynaptic and presynaptic mechanisms. However, the role of these receptors in the regulation of glutamate release, and the net effect of their activation on the excitability of the BLA network are not well understood.

Expression of miRNAs and their cooperative regulation of the pathophysiology in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of injury-related death and disability worldwide. Effective treatment for TBI is limited and many TBI patients suffer from neuropsychiatric sequelae. The molecular and cellular mechanisms underlying the neuronal damage and impairment of mental abilities following TBI are largely unknown.