The effects of anti-histamines on the regional cerebral blood flow during a car driving simulation game

It is well known that anti-histamines have significant CNS side effects such as sleepiness and impaired psychomotor performance, which might induce traffic accidents. There are some reports about the effects of anti-histamines on a car driving performance, but the mechanism has not been understood yet. We examined the changes of the regional cerebral blood flow (rCBF) during a simulated car driving after oral administration of sedative anti-histamine by positron emission tomography (PET). Right-handed, healthy male volunteers (n=7, age 20-25 y. o. ) performed a car driving on a simulated game after oral administration of d-chlorpheniramine (6mg) and placebo. Their rCBF was examined during 1) rest with closed eye, 2) playing a game (active driving) by PET with H2 15O. After oral administration of placebo, the significant increase of rCBF was found in the occipital lobe (Brodmann Area 17, 18, 19), parietal lobe (BA 7) and cerebellum during active driving compared with the resting condition(p<0. 001). Compared to placebo, d- chlorpheniramine produced the significant increase of rCBF in the frontal lobe (BA 6, 8, 9, 11) and temporal lobe (BA 21) during active driving(p<0. 005). It suggests that more attention to visual perception, decision and sensori- motor control is needed after administration of anti- histamines than placebo

Postoperative Cognitive Dysfunction is Correlated with Urine Formaldehyde in Elderly Noncardiac Surgical Patients

Post-operative cognitive dysfunction (POCD), especially in elderly patients, has been reported in many studies. Although increasing age, duration of anesthesia, postoperative infections, and respiratory complications were regarded as the risk factors for POCD, no extracerebral diagnostic biomarkers have been identified as indicators of POCD. Ninety-five patients, ages 65-80 years, scheduled for major orthopedic or abdominal surgery were enrolled. Twenty-two patients aged between 20 and 40 years undergoing the same procedures served as controls. Subjects received neuropsychological tests one-day prior and one week post procedure. To determine the presence of POCD, the criteria were used as described in most previous studies. Morning urine samples were obtained one day before surgery and on day 1, day 2 and day 7 post operatively. Urine formaldehyde was determined with high-performance liquid chromatography. The urine formaldehyde level of all patients with and without POCD increased on the first 2 days after surgery. But the formaldehyde concentration (on day 7) in patients with POCD was significantly higher than that in patients without POCD (p &lt; 0.01). In the young control group, no patient was diagnosed with POCD. Although the changes in urine formaldehyde of young patients during perioperative period were similar to those in elderly patients without POCD, the formaldehyde concentrations measured at four time points were all significantly lower than those in elderly patients (p &lt; 0.05). Levels of urine formaldehyde were elevated in the perioperative period, with the highest levels at day 7 in patients with POCD. This suggests that the increase on day 7 may provide a new physiologic marker along with neuropsychological assessments to assist in the diagnosis of POCD

Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility

Corticotropin-releasing factor (CRF), the stress-related neuropeptide, acts as a neurotransmitter in the brain norepinephrine nucleus, locus coeruleus (LC), to activate this system during stress. CRF shifts the mode of LC discharge from a phasic to a high tonic state that is thought to promote behavioral flexibility. To investigate this, the effects of CRF administered either intracerebroventricularly (30-300 ng, i.c.v.) or directly into the LC (intra-LC; 2-20 ng) were examined in a rat model of attentional set shifting. CRF differentially affected components of the task depending on dose and route of administration. Intracerebroventricular CRF impaired intradimensional set shifting, reversal learning, and extradimensional set shifting (EDS) at different doses. In contrast, intra-LC CRF did not impair any aspect of the task. The highest dose of CRF (20 ng) facilitated reversal learning and the lowest dose (2 ng) improved EDS. The dose-response relationship for CRF on EDS performance resembled an inverted U-shaped curve with the highest dose having no effect. Intra-LC CRF also elicited c-fos expression in prefrontal cortical neurons with an inverted U-shaped dose-response relationship. The number of c-fos profiles was positively correlated with EDS performance. Given that CRF excites LC neurons, the ability of intra-LC CRF to activate prefrontal cortical neurons and facilitate EDS is consistent with findings implicating LC-norepinephrine projections to medial prefrontal cortex in this process. Importantly, the results suggest that CRF release in the LC during stress facilitates shifting of attention between diverse stimuli in a dynamic environment so that the organism can adapt an optimal strategy for coping with the challenge. Neuropsychopharmacology (2012) 37, 520-530; doi:10.1038/npp.2011.218; published online 12 October 201