Elemental Mapping in a Preclinical Animal Model Reveals White Matter Copper Elevation in the Acute Phase of Central Nervous System Trauma.

Understanding the chemical events following trauma to the central nervous system could assist in identifying causative mechanisms and potential interventions to protect neural tissue. Here, we apply a partial optic nerve transection model of injury in rats and use synchrotron X-ray fluorescence microscopy (XFM) to perform elemental mapping of metals (K, Ca, Fe, Cu, Zn) and other related elements (P, S, Cl) in white matter tracts. The partial optic nerve injury model and spatial precision of microscopy allow us to obtain previously unattained resolution in mapping elemental changes in response to a primary injury and subsequent secondary effects.

Cannabinoids in traumatic brain injury and related neuropathologies: preclinical and clinical research on endogenous, plant-derived, and synthetic compounds.

Traumatic brain injury is common, and often results in debilitating consequences. Even mild traumatic brain injury leaves approximately 20% of patients with symptoms that persist for months. Despite great clinical need there are currently no approved pharmaceutical interventions that improve outcomes after traumatic brain injury.

Maternal Immune Activation during Pregnancy Alters the Behavior Profile of Female Offspring of Sprague Dawley Rats.

Sex differences are documented in psychiatric and neurological disorders, yet most preclinical animal research has been conducted in males only. There is a need to better understand of the nature of sex differences in brain disease in order to meet the needs of psychiatric patients. We present the behavior profile of adult female offspring produced using a maternal immune activation (MIA) model where pregnant rats receive an immune stimulant and the offspring typically show various abnormalities consistent with psychiatric illnesses such as schizophrenia and autism.

Prospective Analysis of the Effects of Maternal Immune Activation on Rat Cytokines during Pregnancy and Behavior of the Male Offspring Relevant to Schizophrenia.

Influenza during pregnancy is associated with the development of psychopathology in the offspring. We sought to determine whether maternal cytokines produced following administration of viral mimetic polyinosinic-polycytidylic acid (polyI:C) to pregnant rats were predictive of behavioral abnormalities in the adult offspring. Timed-pregnant Sprague Dawley rats received a single intravenous injection of 4-mg/kg polyI:C or saline on gestational day (GD)15.

Acute stress, but not corticosterone, facilitates acquisition of paired associates learning in rats using touchscreen-equipped operant conditioning chambers.

Acute stress influences learning and memory in humans and rodents, enhancing performance in some tasks while impairing it in others. Typically, subjects preferentially employ striatal-mediated stimulus-response strategies in spatial memory tasks following stress, making use of fewer hippocampal-based strategies which may be more cognitively demanding. Previous research demonstrated that the acquisition of rodent paired associates learning (PAL) relies primarily on the striatum, while task performance after extensive training is impaired by hippocampal disruption.

Dissociable effects of the - and - enantiomers of govadine on the disruption of prepulse inhibition by MK-801 and apomorphine in male Long-Evans rats.

Rationale: The search for novel antipsychotic drugs to treat schizophrenia is driven by the poor treatment efficacy, serious side effects, and poor patient compliance of current medications. Recently, a class of compounds known as tetrahydroprotoberberines, which includes the compound -govadine, have shown promise in preclinical rodent tests relevant to schizophrenia. To date, the effect of govadine on prepulse inhibition (PPI), a test for sensorimotor gating commonly used to assess the effects of putative treatments for schizophrenia, has not been determined.

Developmental disruption of perineuronal nets in the medial prefrontal cortex after maternal immune activation.

Maternal infection during pregnancy increases the risk of offspring developing schizophrenia later in life. Similarly, animal models of maternal immune activation (MIA) induce behavioural and anatomical disturbances consistent with a schizophrenia-like phenotype in offspring. Notably, cognitive impairments in tasks dependent on the prefrontal cortex (PFC) are observed in humans with schizophrenia and in offspring after MIA during pregnancy.

Mapping Alterations to the Endogenous Elemental Distribution within the Lateral Ventricles and Choroid Plexus in Brain Disorders Using X-Ray Fluorescence Imaging.

The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl-, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI).

Effects of the metabotropic glutamate receptor 5 positive allosteric modulator CDPPB on rats tested with the paired associates learning task in touchscreen-equipped operant conditioning chambers.

Effective treatments for the cognitive symptoms of schizophrenia are critically needed. Positive allosteric modulation (PAM) of metabotropic glutamate receptor subtype 5 (mGluR5) is one strategy currently under investigation to improve these symptoms. Examining cognition using touchscreen-equipped operant chambers may increase translation between preclinical and clinical research through analogous behavioral testing paradigms in rodents and humans.

Effects of D- and L-govadine on the disruption of touchscreen object-location paired associates learning in rats by acute MK-801 treatment.

Rationale: New pharmacological treatments for the cognitive deficits in schizophrenia are needed. Tetrahydroprotoberberines, such as govadine, are one class of compounds with dopaminergic activities that may be useful in treating some aspects of the cognitive symptoms of the disorder.

Objective: The objective of the present studies was to test the effects of the D- and L-enantiomers of govadine on the impairment in a paired-associate learning (PAL) task produced by acute MK-801 in rats.

Altered object exploration but not temporal order memory retrieval in an object recognition test following treatment of rats with the group II metabotropic glutamate receptor agonist LY379268.

Temporal order memory refers to the ability to distinguish past experiences in the order that they occurred. Temporal order memory for objects is often tested in rodents using spontaneous object recognition paradigms. The circuitry mediating memory in these tests is distributed and involves ionotropic glutamate receptors in the perirhinal cortex and medial prefrontal cortex.