Background: Stroke is a multisystemic disorder that includes mechanisms of thrombosis and neurotoxic coupling. Key metabolites of the molecular cascade following biochemical events appear simultaneously in brain tissue, the blood-brain barrier, and brain vessels, activating the immune system and generating autoantibodies (aAbs) to brain-specific antigens. We developed an ELISA blood test to measure aAbs to a subtype of N-methyl-D-aspartate (NMDA) receptors, which are the key markers of neurotoxicity underlying cerebral ischemia. We investigated the diagnostic accuracy of serum aAbs to NR2A/2B, a subtype of NMDA receptors, in assessing transient ischemic attack (TIA) and ischemic stroke (IS) and its ability to distinguish cerebral ischemia from intracerebral hemorrhage (ICH). Methods: Autoantibodies to NR2A/2B were measured in 360 serum samples: 105 from TIA/stroke patients and 255 from controls, including patients with controlled hypertension/atherosclerosis and gender-and agematched healthy individuals. Results: Patients with TIA (n ‫؍‬ 56) and acute IS (n ‫؍‬ 31) had significantly higher NR2A/2B aAb concentrations than controls (P <0.0001). The test sensitivities for TIA and IS were 95% and 97%, respectively, and predictive values were 86% and 91% at a cutoff point of 2.0 g/L. The area under the ROC curve was 0.99. Monitoring NR2A/2B aAbs within 72 h differentiated IS and ICH (P

People are very likely to start psychoactive drug use during adolescence, an earlier onset being associated with a higher risk of developing addiction later in life. In experiment I, Pre-(postnatal day (pnd) 23-35), Mid-(pnd 36-48), or Post-(pnd 49-61) adolescent mice underwent a restricted-drinking period (2 h/day for 12 days), one bottle containing water and the other containing nicotine (10 mg/l) or water. After this period, Mid-adolescents showed prominent exploration and reduced anxiety in the plus-maze. This ontogenetic profile was dampened by nicotine consumption. After 2 months, these mice were tested in a novel environment (30 min/day for 3 days). Locomotor-habituation profiles were specifically disrupted by nicotine consumption during Mid-adolescence, suggesting this age as a critical period. In experiment II, Mid-adolescent (pnd 35-44) and adult (pnd 470) mice were pretreated with nicotine (0, 0.03, 0.10, 0.30 mg/kg/day for 10 days). Acute nicotine administration had opposite effects on anxiety in adolescents and adults. At 2 months after pretreatment, we measured levels of AMPA GluR2/3 subunits, thought to be involved in the control of addictive behaviors. Nicotine exposure during Mid-adolescence dose-dependently downregulated these subunits in the striatum and hippocampus, but comparable exposure during adulthood had either opposite or no effects. NMDA NR2A/B subunits were affected by nicotine, but without agerelated differences. The present data identified a nicotine-vulnerable age window, characterized by long-term disruption of locomotor habituation and downregulation of AMPA receptors. These findings support neurobiological vulnerability to drugs in adolescent humans.

Background and Purpose-The goal of this study was to compare the predictive ability of S100B, N-methyl-D-aspartate (NMDA) receptor antibodies (NR2Ab) and C-reactive protein (CRP) for neurological deficits after cardiac surgery with cardiopulmonary bypass (CPB). Methods-We investigated 557 high-risk adult patients who underwent coronary artery or valve replacement surgery using CPB as a substudy of a prospective, blinded, multicenter clinical trial. Serum concentrations of S100B (nϭ513 patients), NR2Ab (nϭ398) and CRP (nϭ510) were measured preoperatively, 24 and 48 hours after CPB. Neurological adverse events were assessed at baseline and postoperative days 1 and 2; neurocognitive function (mini-mental status examination) was assessed at baseline and on postoperative days 1, 7 and 28. Results-Fifty-five (9.9%) patients had moderate or severe neurological adverse events (confusion/delirium, transient ischemic attack, or stroke) within 48 hours of CPB. Women had significantly more neurological complications than men (15.5% versus 7.8%; Pϭ0.007). Ninety-six percent (24/25) of patients with NR2Ab concentrations Ն2.0 ng/mL preoperatively had neurological complications within 48 hours post-CPB, versus only 5.4% (20/373) of patients with NR2Ab concentrations Ͻ2.0 ng/mL, resulting in a 17.9-fold increase (95% CI, 11.6 to 27.6) in postoperative neurological complications for patients with high levels of NR2A antibodies. Preoperative serum S100B and CRP did not predict neurological complications from CPB. Decreased mini-mental status examination scores for orientation, attention and recall were associated with neurological adverse events early after CPB. Conclusions-Preoperative serum concentrations of NR2Ab, but not S100B or CRP, are predictive of severe neurological adverse events after CPB. Patients with a positive NR2Ab test (Ն2.0 ng/mL) preoperatively were nearly 18 times more likely to experience a postoperative neurological event than patients with a negative test (Ͻ2.0 ng/mL). Key Words: brain ischemia Ⅲ cardiac surgery Ⅲ cardiopulmonary bypass N eurological complications after cardiac surgery are now recognized as a serious and costly healthcare problem. The incidence of stroke ranges between 1% and 5.2% during the perioperative period, 1-5 postoperative delirium occurs in 10% to 30%, 6 and cognitive changes are reported in 33% to 83% of patients. 3,4 The impact on the patient's family, postoperative care, prolonged hospitalization and costs are enormous. Roach et al 6 reported a 6.1% incidence of serious adverse neurological events in a survey of 2108 patients undergoing coronary artery bypass surgery (CABG) at 24 US hospitals. Patients experiencing neurological complications had significantly prolonged hospitalization and 47% were transferred to a chronic care facility. A blood test that can reliably predict who is at risk for neurological complications from heart surgery is presently not available.During the last decade several biomarkers to predict and diagnose brain injury have been proposed. Serum S100B, a c...

These findings indicate an altered response to morphine-related reinforcing and aversive effects in MDOR mice and altered coping with the environment in GluR1 mice. Circulating aAbs to specific neuroreceptors may alter the response to opiates and play a role as determinants of vulnerability to opiate addiction.