Mechanistic and therapeutic relationships of traumatic brain injury and γ-amino-butyric acid (GABA).

Traumatic brain injury (TBI) is a highly prevalent medical condition for which no medications specific for the prophylaxis or treatment of the condition as a whole exist. The spectrum of symptoms includes coma, headache, seizures, cognitive impairment, depression, and anxiety. Although it has been known for years that the inhibitory neurotransmitter γ-amino-butyric acid (GABA) is involved in TBI, no novel therapeutics based upon this mechanism have been introduced into clinical practice.

Neuropeptide and cytokine regulation of pain in the context of substance use disorders.

Substance use disorders (SUDs) are frequently accompanied by affective symptoms that promote negative reinforcement mechanisms contributing to SUD maintenance or progression. Despite their widespread use as analgesics, chronic or excessive exposure to alcohol, opioids, and nicotine produces heightened nociceptive sensitivity, termed hyperalgesia. This review focuses on the contributions of neuropeptide (CRF, melanocortin, opioid peptide) and cytokine (IL-1β, TNF-α, chemokine) systems in the development and maintenance of substance-induced hyperalgesia.

Culture Model for Non-human Primate Choroid Plexus.

While there are murine and rat choroid plexus epithelial cell cultures, a translationally relevant model for choroid plexus activation and function is still lacking. The rhesus macaque is the gold standard for modeling viral infection and activation of CNS, including HIV-associated neurocognitive disorders. We have developed a rhesus macaque choroid plexus epithelial cell culture model which we believe to be suitable for studies of inflammation associated with viral infection of the CNS.

Lack of susceptibility in neonatally infected rhesus macaques to simian immunodeficiency virus-induced encephalitis.

Despite combination antiretroviral therapies making HIV a chronic rather than terminal condition for many people, the prevalence of HIV-associated neurocognitive disorders (HAND) is increasing. This is especially problematic for children living with HIV. Children diagnosed HAND rarely display the hallmark pathology of HIV encephalitis in adults, namely infected macrophages and multinucleated giant cells in the brain.

Chronic Viral Neuroinflammation: Speculation on Underlying Mechanisms.

Viral infection in the brain can be acute or chronic, with the responses often producing foci of increasingly cytotoxic inflammation. This can lead to effects beyond the central nervous system (CNS). To stimulate discussion, this commentary addresses four questions: What drives the development of human immunodeficiency virus (HIV)-associated neurocognitive disorders, does the phenotype of macrophages in the CNS spur development of HIV encephalitis (HIVE), does continual activation of astrocytes drive the development of HIV-associated neurocognitive disorders/subclinical disease, and neuroinflammation: friend or foe? A unifying theory that connects each question is the issue of continued activation of glial cells, even in the apparent absence of simian immunodeficiency virus/HIV in the CNS.