Current neurological observations and complications of dengue virus infection.

Dengue, a mosquito-borne flavivirus and fastest growing tropical disease in the world, has experienced an explosion of neurologic case reports and series in recent years. Now dengue is a frequent or leading cause of encephalitis in some endemic regions, is estimated to infect one in six tourists returning from the tropics, and has been proven to have local transmission within the continental USA. High documentation of neurologic disease in recent years reflects increases in overall cases, enhanced clinical awareness and advances in diagnostics.

Neurologic infections in diabetes mellitus.

Even at a time when HIV/AIDS and immunosuppressive therapy have increased the number of individuals living with significant immunocompromise, diabetes mellitus (DM) remains a major comorbid disorder for several rare but potentially lethal infections, including rhino-orbital-cerebral mucormycosis and malignant external otitis. DM is also a commonly associated condition in patients with nontropical pyomyositis, pyogenic spinal infections, Listeria meningitis, and blastomycosis. As West Nile virus spread to and across North America over a decade ago, DM appeared in many series as a risk factor for death or neuroinvasive disease.

Juvenile cannabinoid treatment induces frontostriatal gliogenesis in Lewis rats.

Cannabis abuse in adolescence is associated with a broad array of phenotypical consequences, including a higher risk for schizophrenia and other mental disturbances related to dopamine (DA) imbalances. The great variability of these sequelae likely depends on the key influence of diverse genetic vulnerability factors. Inbred rodent strains afford a highly informative tool to study the contribution of genetic determinants to the long-term effects of juvenile cannabinoid exposure.

Prospects for cannabinoid therapies in viral encephalitis.

Cannabinoids are promising therapies to support neurogenesis and decelerate disease progression in neuroinflammatory and degenerative disorders. Whether neuroprotective effects of cannabinoids are sustainable during persistent viral infection of the CNS is not known. Using a rodent model of chronic viral encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective (Solbrig et al.

A synthetic cannabinoid agonist promotes oligodendrogliogenesis during viral encephalitis in rats.

Chronic CNS infection by several families of viruses can produce deficits in prefrontal cortex (PFC) and striatal function. Cannabinoid drugs have been long known for their anti-inflammatory properties and their ability to modulate adult neuro and gliogenesis. Therefore, we explored the effects of systemic administration of the cannabinoid agonist WIN55,212-2(WIN) on prefrontal cortex (PFC) and striatal cytogenesis in a viral model of CNS injury and inflammation based on Borna Disease (BD) virus encephalitis.

Animal models of CNS viral disease: examples from borna disease virus models.

Borna disease (BD), caused by the neurotropic RNA virus, Borna Disease virus, is an affliction ranging from asymptomatic to fatal meningoencephalitis across naturally and experimentally infected warmblooded (mammalian and bird) species. More than 100 years after the first clinical descriptions of Borna disease in horses and studies beginning in the 1980's linking Borna disease virus to human neuropsychiatric diseases, experimentally infected rodents have been used as models for examining behavioral, neuropharmacological, and neurochemical responses to viral challenge at different stages of life. These studies have contributed to understanding the role of CNS viral injury in vulnerability to behavioral, developmental, epileptic, and neurodegenerative diseases and aided evaluation of the proposed and still controversial links to human disease.

Cannabinoid rescue of striatal progenitor cells in chronic Borna disease viral encephalitis in rats.

A growing number of environmental and pharmacologic manipulations have been shown to influence adult neurogenesis. Borna disease virus (BDV) in rats causes cortical and subcortical infection with extrapyramidal motor symptoms, and hippocampal infection suppresses neurogenesis. Given the known effects of cannabinoids in promoting neural progenitor cell survival, the authors examined in vivo effects of chronic BDV infection in rats on BrdU-positive progenitor cells in striatum, together with neuroprotective actions of cannabinoids.

CNS viruses--diagnostic approach.

Diagnosis of CNS viral infections is challenging; yet, significant progress in laboratory diagnosis of CNS infections has come through applications of serology and polymerase chain reaction (PCR) to CSF and tissues. Advances in molecular and laboratory techniques, together with neuroimaging, epidemiologic, and surveillance efforts, are yielding greater success in CNS viral diagnosis and treatment.

Refractory status epilepticus in suspect encephalitis.

Background: The California Encephalitis Project (CEP) is a program designed to determine causes of encephalitis. We sought to determine whether there are any distinguishing characteristics of patients with encephalitis who develop refractory status epilepticus from those who do not.

Methods: Data from all patients in the CEP were retrospectively reviewed and analyzed.

The price of seizure control: dynorphins in interictal and postictal psychosis.

Postictal and interictal psychoses are relatively common complicating factors in the clinical course of epilepsy, yet their neurobiological substrates are poorly understood. Recent evidence shows that kappa opioid receptor (KOR) activation elicits anticonvulsant and psychotomimetic effects. In view of this background, here we introduce the hypothesis that epilepsy-related psychoses may partially result from excessive hippocampal dynorphin release and kappa opioid receptor overstimulation aimed at seizure control.

Activators of potassium M currents have anticonvulsant actions in two rat models of encephalitis.

Opioid systems in hippocampus regulate excitability and kappa opioids have a role in anticonvulsant protection, but their mechanisms of action are incompletely understood. We examined the ability of opioid and nonopioid agents with overlapping ionic mechanisms and actions similar to kappa opioid agonists, to block seizures in rat models of encephalitis due to Borna Disease virus and Herpes Simplex Virus Type-1. Naltrindole, a delta antagonist and thus a kappa opioid sparing agent, (10 mg/kg s.

Viral risk factor for seizures: pathobiology of dynorphin in herpes simplex viral (HSV-1) seizures in an animal model.

Up to 89% of patients with herpes simplex virus type-1 (HSV-1) encephalitis can have seizures. Possibly, viruses are environmental triggers for seizures in genetically vulnerable individuals. Inherited dynorphin promoter polymorphisms are associated with temporal lobe epilepsy and febrile seizures in man.

Kappa opioid control of seizures produced by a virus in an animal model.

Epilepsy remains a major medical problem of unknown aetiology. Potentially, viruses can be environmental triggers for development of seizures in genetically vulnerable individuals. An estimated half of encephalitis patients experience seizures and approximately 4% develop status epilepticus.

A role for endocannabinoids in viral-induced dyskinetic and convulsive phenomena.

Dyskinesias and seizures are both medically refractory disorders for which cannabinoid-based treatments have shown early promise as primary or adjunctive therapy. Using the Borna disease (BD) virus rat, an animal model of viral encephalopathy with spontaneous hyperkinetic movements and seizure susceptibility, we identified a key role for endocannabinoids in the maintenance of a balanced tone of activity in extrapyramidal and limbic circuits. BD rats showed significant elevations of the endocannabinoid anandamide in subthalamic nucleus, a relay nucleus compromised in hyperkinetic disorders.

Epilepsy, CNS viral injury and dynorphin.

Epilepsy is a significant health problem. Despite the widespread use of both classic and newer pharmacological agents that target ion channels, amino acid transmission or receptors, there are numerous examples of mono- or polytherapy being ineffective. Seizures that are secondary to CNS infections are among the most refractory medically, and thus insult-specific agents are desirable.

Neuropharmacological sequelae of persistent CNS viral infections: lessons from Borna disease virus.

Borna Disease Virus (BDV) is a neurotropic RNA virus that is worldwide in distribution, causing movement and behavior disorders in a wide range of animal species. BDV has also been reported to be associated with neuropsychiatric diseases of humans by serologic study and by recovery of nucleic acid or virus from blood or brain. Natural infections of horses and sheep produce encephalitis with erratic excited behaviors, hyperkinetic movement or gait abnormalities; naturally infected cats have ataxic "staggering disease.

Key role for enkephalinergic tone in cortico-striatal-thalamic function.

Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions.

Neuroprotection and reduced proliferation of microglia in ribavirin-treated bornavirus-infected rats.

In a rat model of Borna disease, intracerebral ribavirin caused clinical improvement without changes in virus titer or nucleic acid. Levels of microglia and infiltrating CD4 and CD8 cells were decreased, despite increases in mRNAs encoding interleukin-1beta (IL-1beta), IL-10, and gamma interferon in the brain. Intracerebral ribavirin may reduce morbidity through effects on microglia cell proliferation.