ABSTRACT
Phencyclidine (PCP) is a non-competitive NMDA glutamate receptor antagonist that induces psychotomimetic effects in humans and experimental animals. Chronic PCP exposure elicits signs of persistently altered frontal brain activity and related behaviors which are also seen in patients with schizophrenia. Secretogranin II (sg II) belongs to the chromogranin family of proteins that exist in large dense core vesicles in nervous tissue. In the brain, 90% of sg II is processed to the small peptide secretoneurin. We previously detected differential effects of single-dose and subchronic PCP administration on sg II expression in the rat prefrontal cortex (PFC). In the present study, we applied PCP to organotypic PFC slices. PCP application for 28 h induced decreased tissue and culture medium secretoneurin content. In contrast, incubation with the adenylate cyclase activator forskolin caused significantly increased secretoneurin levels after 8 h. PCP for 4 h followed by 24 h without PCP resulted in increased culture medium secretoneurin content but no change in tissue levels. sg II mRNA expression was decreased after 28 h PCP application in cortical neurons. Immunohistochemical and TUNEL staining profiles indicated that the alterations were not due to neurodegeneration. PCP for 5 days changed neither the secretoneurin tissue or culture medium levels, nor the sg II mRNA expression. These results demonstrate that PCP modulates sg II expression in PFC tissue in the absence of afferent inputs and that the nature of these changes is dependent upon the duration of exposure to and/or withdrawal from PCP.
Subject(s)
Hallucinogens/pharmacology , Phencyclidine/pharmacology , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Proteins/genetics , Animals , Chromogranin B , Chromogranins/metabolism , Colforsin/pharmacology , In Situ Nick-End Labeling , In Vitro Techniques , Interneurons/cytology , Interneurons/drug effects , Interneurons/metabolism , Male , Neuropeptides/metabolism , Peptide Fragments/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Secretogranin IIABSTRACT
OBJECTIVE: Patients sustaining facial fractures are at risk for accompanying traumatic intracranial hematomas, which are a major cause of morbidity and mortality. Prompt recognition is crucial in improving patient survival and recovery. This study examined which simple clinical signs identify facial fracture patients at risk for intracranial hemorrhage before the performance of computed tomography. DESIGN AND METHODS: Retrospective study of 2,195 patients with facial fractures during a period of 7 years. By means of univariate and multivariate analysis clinical features potentially predictive for (a) intracranial hemorrhage and (b) surgery for intracranial hemorrhage were identified. SETTING: Critical care units of anesthesiology and neurology, general traumatology, and oral and maxillofacial surgery in a level I trauma university hospital. RESULTS: Seizures (OR 22.1) and vomiting/nausea (OR 20.2) were the strongest independent predictors of intracranial bleeding in facial fracture patients. For intracranial hemorrhages requiring surgical intervention closed head injuries (OR 9.75) and cranial vault fractures (OR 5.0) were the most significant risk factors. However, among those patients without vomiting/nausea and without seizures and without closed head injury ( n=1,628), 20 patients (1.2%) suffered intracranial hemorrhage, and six (0.37%) of them required surgical intervention. CONCLUSIONS: Simple clinical symptoms, such as seizures, vomiting/nausea, history of a closed head injury or cranial vault fractures are strong predictors for intracranial hemorrhage in facial fracture patients. The early consideration of such important indicators allows us to detect patients at elevated risk of an intracranial hematoma requiring surgical intervention.
