SUMMARY Zika virus (ZIKV) is an emerging flavivirus that causes congenital abnormalities and Guillain-Barré syndrome. ZIKV infection also results in severe eye disease characterized by optic neuritis, chorioretinal atrophy, and blindness in newborns and conjunctivitis and uveitis in adults. We evaluated ZIKV infection of the eye using recently developed mouse models of pathogenesis. ZIKV-inoculated mice developed conjunctivitis, pan-uveitis and infection of the cornea, iris, optic nerve, and the ganglion and bipolar cells in the retina. This phenotype was independent of the entry receptors Axl or Mertk, as Axl−/−, Mertk−/− or Axl−/− Mertk−/− DKO mice sustained similar levels of infection as control animals. We also detected abundant viral RNA in tears, suggesting that virus may be secreted from lacrimal glands or shed from the cornea. This model provides a foundation for studying ZIKV-induced ocular disease, defining mechanisms of viral persistence, and developing therapeutic approaches for viral infections of the eye.

A 3 h exposure to ISO is sufficient to induce widespread neurotoxicity in the developing primate brain. These results are relevant for clinical medicine, as many surgical and diagnostic procedures in children require anaesthesia durations similar to those modelled here. Further research is necessary to identify long-term neurobehavioural consequences of 3 h ISO exposure.

Previously we reported that a 5-hour exposure of 6-day-old (P6) rhesus macaques to isoflurane triggers robust neuron and oligodendrocyte apoptosis. In an attempt to further describe the window of vulnerability to anesthetic neurotoxicity, we exposed P20 and P40 rhesusmacaques to 5 h of isoflurane anesthesia or no exposure (control animals). Brains were collected 3 h later and examined immunohistochemically to analyze neuronal and glial apoptosis. Brains exposed to isoflurane displayed neuron and oligodendrocyte apoptosis distributed throughout cortex and white matter, respectively. When combining the two age groups (P20 + P40), the animals exposed to isoflurane had 3.6 times as many apoptotic cells as the control animals. In the isoflurane group, approximately 66% of the apoptotic cells were oligodendrocytes and 34% were neurons. In comparison, in our previous studies on P6 rhesusmacaques, approximately 52% of the dying cells were glia and 48% were neurons. In conclusion, the present data suggest that the window of vulnerability for neurons is beginning to close in the P20 and P40 rhesus macaques, but continuing for oligodendrocytes.

A common remark among laypeople, and notably also among mental health workers, is that individuals with mental illnesses use drugs as self-medication to allay clinical symptoms and the side effects of drug treatments. Roots of the self-medication concept in psychiatry date back at least to the 1980s. Observations that rates of smokers in schizophrenic patients are multiple times the rates for regular smoking in the general population, as well as those with other disorders, proved particularly tempting for a self-medication explanation. Additional evidence came from experiments with animal models exposed to nicotine and the identification of neurobiological mechanisms suggesting self-medication with smoking is a plausible idea. More recently, results from studies comparing smoking and non-smoking schizophrenic patients have led to the questioning of the self-medication hypothesis. Closer examination of the literature points to the possibility that smoking is less beneficial on schizophrenic symptomology than generally assumed while clearly increasing the risk of cancer and other smoking-related diseases responsible for early mortality. It is a good time to examine the evidence for the self-medication concept as it relates to smoking. Our approach is to focus on data addressing direct or implied predictions of the hypothesis in schizophrenic smokers.

Background and Purpose Neuroactive steroid (3β,5β,17β)‐3‐hydroxyandrostane‐17‐carbonitrile (3β‐OH) is a novel hypnotic and voltage‐dependent blocker of T‐type calcium channels. Here, we examine its potential analgesic effects and adjuvant anaesthetic properties using a post‐surgical pain model in rodents. Experimental Approach Analgesic properties of 3β‐OH were investigated in thermal and mechanical nociceptive tests in sham or surgically incised rats and mice, with drug injected either systemically (intraperitoneal) or locally via intrathecal or intraplantar routes. Hypnotic properties of 3β‐OH and its use as an adjuvant anaesthetic in combination with isoflurane were investigated using behavioural experiments and in vivo EEG recordings in adolescent rats. Key Results A combination of 1% isoflurane with 3β‐OH (60 mg·kg−1, i.p.) induced suppression of cortical EEG and stronger thermal and mechanical anti‐hyperalgesia during 3 days post‐surgery, when compared to isoflurane alone and isoflurane with morphine. 3β‐OH exerted prominent enantioselective thermal and mechanical antinociception in healthy rats and reduced T‐channel‐dependent excitability of primary sensory neurons. Intrathecal injection of 3β‐OH alleviated mechanical hyperalgesia, while repeated intraplantar application alleviated both thermal and mechanical hyperalgesia in the rats after incision. Using mouse genetics, we found that CaV3.2 T‐calcium channels are important for anti‐hyperalgesic effect of 3β‐OH and are contributing to its hypnotic effect. Conclusion and Implications Our study identifies 3β‐OH as a novel analgesic for surgical procedures. 3β‐OH can be used to reduce T‐channel‐dependent excitability of peripheral sensory neurons as an adjuvant for induction and maintenance of general anaesthesia while improving analgesia and lowering the amount of volatile anaesthetic needed for surgery.