Decreased survival of newborn neurons in the dorsal hippocampus after neonatal LPS exposure in mice.

Experimental studies show that inflammation reduces the regenerative capacity in the adult brain. Less is known about how early postnatal inflammation affects neurogenesis, stem cell proliferation, cell survival and learning and memory in young adulthood. In this study we examined if an early-life inflammatory challenge alters cell proliferation and survival in distinct anatomical regions of the hippocampus and whether learning and memory were affected. Lipopolysaccharide (LPS, 1mg/kg) was administered to mice on postnatal day (P) 9 and proliferation and survival of hippocampal cells born either prior to (24h before LPS), or during the inflammatory insult (48 h after LPS) was evaluated. Long-term cell survival of neurons and astrocytes was determined on P 41 and P 60 in the dorsal and ventral horns of the hippocampus. On day 50 the mice were tested in the trace fear conditioning (TFC) paradigm. There was no effect on the survival of neurons and astrocytes that were born before LPS injection. In contrast, the number of neurons and astrocytes that were born after LPS injection were reduced on P 41. The LPS-induced reduction in cell numbers was specific for the dorsal hippocampus. Neither early (48 h after LPS) or late (33 days after LPS) proliferation of cells was affected by neonatal inflammation and neonatal LPS did not alter the behavior of young adult mice in the TFC test. These data highlight that neonatal inflammation specifically affects survival of dividing neurons and astrocytes, but not post-mitotic cells. The reduction in cell survival could be attributed to less cell survival in the dorsal hippocampus, but had no effect on learning and memory in the young adult.

The neural and vascular effects of killed Su-Streptococcus pyogenes (OK-432) in preterm fetal sheep.

Fetal exposure to inflammatory mediators is associated with a greater risk of brain injury and may cause endothelial dysfunction; however, nearly all the evidence is derived from gram-negative bacteria. Intrapleural injections of OK-432, a killed Su-strain of Streptococcus pyogenes, has been used to treat fetal chylothorax. In this study, we evaluated the neural and cardiovascular effects of OK-432 in preterm fetal sheep (104 +/- 1 days, term 147 days). OK-432 (0.1 mg, n = 6) or saline vehicle (n = 7) was infused in the fetal pleura, and fetuses were monitored for 7 days. Blood samples were taken routinely for plasma nitrite measurement. Fetal brains were taken for histological assessment at the end of the experiment. Between 3 and 7 h postinjection, OK-432 administration was associated with transient suppression of fetal body and breathing movements and electtroencephalogram activity (P < 0.05), increased carotid and femoral vascular resistance (P < 0.05), but no change in blood pressure. Brain activity and behavior then returned to normal except in one fetus that developed seizures. OK-432 fetuses showed progressive, sustained vasodilatation (P < 0.05), with lower blood pressure after 4 days (P < 0.05), but normal heart rate. There were no changes in plasma nitrite levels. Histological studies showed bilateral infarction in the dorsal limb of the hippocampus of the fetus that developed seizures, but no injury in other fetuses. We conclude that a single low-dose injection of OK-432 can be associated with risk of focal cerebral injury in the preterm fetus and chronic central and peripheral vasodilatation that does not appear to be mediated by nitric oxide.

Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action.

Adult hippocampal neurogenesis, a once unorthodox concept, has changed into one of the most rapidly growing fields in neuroscience. The present report results from the ECNP targeted expert meeting in 2007 during which cellular plasticity changes were addressed in the adult brain, focusing on neurogenesis and apoptosis in hippocampus and frontal cortex. We discuss recent studies investigating factors that regulate neurogenesis with special emphasis on effects of stress, sleep disruption, exercise and inflammation, a group of seemingly unrelated factors that share at least two unifying properties, namely that they all regulate adult hippocampal neurogenesis and have all been implicated in the pathophysiology of mood disorders. We conclude that although neurogenesis has been implicated in cognitive function and is stimulated by antidepressant drugs, its functional impact and contribution to the etiology of depression remains unclear. A lasting reduction in neurogenesis following severe or chronic stress exposure, either in adult or early life, may represent impaired hippocampal plasticity and can contribute to the cognitive symptoms of depression, but is, by itself, unlikely to produce the full mood disorder. Normalization of reductions in neurogenesis appears at least partly, implicated in antidepressant action.

Effect of exercise on ovarian morphology and expression of nerve growth factor and alpha(1)- and beta(2)-adrenergic receptors in rats with steroid-induced polycystic ovaries.

Oestadiol valerate (EV)-induced polycystic ovaries (PCO) in rats cause anovulation and cystic ovarian morphology. Denervation of ovarian sympathetic nerves restores ovulatory disruption. In the present study, we determined whether 5 weeks of voluntary exercise influence ovarian morphology and the expression of sympathetic markers in the EV-induced PCO rat model. The effect of exercise on (i) ovarian morphology; (ii) mRNA and protein expression of nerve growth factor (NGF); and (iii) mRNA and number of ovarian-expressing cells for the NGF receptor (p75 neurotrophin receptor) and the alpha(1a)-, alpha(1b)-, alpha(1d)- and beta(2)-adrenergic receptors (ARs) in rats with EV-induced PCO was evaluated. PCO was induced by a single i.m. injection of EV, and controls were injected with oil alone in adult cycling rats. The rats were divided into four groups: (i) control (oil); (ii) exercise group (oil + exercise); (iii) a PCO group (EV); and (iv) a PCO exercise group (EV + exercise). The exercise and PCO exercise groups ran voluntarily for 5 weeks in computer-monitored wheels placed in the cages where they were housed. The results obtained indicated that ovarian morphology was almost normalised in the PCO exercise group; NGF mRNA and protein concentrations were normalised in the PCO exercise group; high numbers of NGF receptor expressing cells in PCO ovaries were lowered by exercise; and the number of immunopositive cells of the different AR subtypes were all reduced after exercise in the PCO group, except for the alpha(1b)- and beta(2)-AR whereas the mRNA levels were unaffected, indicating transcriptional regulation. In conclusion, our data indicate a beneficial effect of regular exercise, as a modulator of ovarian sympathetic innervation, in the prevention and treatment of human PCOS.

[Psychiatric morbidity in connection with surgical treatment of epilepsy. A short-term follow-up of patients with amygdalohippocampectomy]. / Psykiatrisk morbiditet i forbindelse med epilepsikirurgi. Korttidsopfølgning af amygdalohippokampektomerede patienter.

The aim of the study was to examine the occurrence of psychiatric disorders in epilepsy patients who had received surgical treatment, especially amygdalohippocampectomy (AHE), for the relief of medically intractable seizures. Forty-seven subjects, treated during the period 1987-1991 in the Danish epilepsy surgery programme (EPIKIR), entered a retrospective interview study. Of these, 37 had undergone AHE. Preoperative psychiatric morbidity was assessed through interview and available case notes, including a routine psychiatric interview. Postoperative psychiatric morbidity was assessed by the use of the Present State Examination. A total of six subjects (five AHE subjects) developed depressive disorders of various duration and severity after operation. In three subjects this occurred "de novo". No paranoid-hallucinatory psychoses developed within the follow-up period (a minimum of one year), and the presence of psychiatric disorders could not be associated with either lateralization of cerebral dominance of histopathological findings. Thus, depression appears to be the most frequent psychiatric problem following epilepsy surgery. Although the present study mainly deals with AHE, this finding is in accordance with the results of recent findings concerning anterior temporal lobe resection.

Psychiatric morbidity after surgery for epilepsy: short-term follow up of patients undergoing amygdalohippocampectomy.

The aim was to assess the occurrence and type of psychiatric disorders of patients with medically intractable epilepsy in relation to surgical treatment, with special reference to amygdalohippocampectomy (AHE). The design was a retrospective psychiatric interview study, including Present State Examination (PSE) and diagnostic classification according to the International Classification of Diseases--8th revision (ICD-8) and ICD-10. Forty seven (94% of total) patients operated on between 1987 and mid-1991 in the Danish epilepsy surgery programme were studied. The main group of interest included 37 patients treated by AHE. The presence of psychiatric disorders before and after operation was assessed by PSE (including the Catego classification) and by ordinary clinical procedures, making use of all available information (hospital case notes and presurgical psychiatric assessments independent of the study). Four patients in the AHE group developed depressive disorders of various durations and severity after operation (in three (8%) patients these occurred de novo). One other patient with AHE with a presumed personality disorder who underwent AHE developed a severe depression, as did one patient after a lesionectomy. No patients developed new paranoid hallucinatory psychoses. No association was found between presence of psychiatric disorders and neither right sided cerebral dominance nor histopathological findings. In conclusion, the postoperative psychiatric morbidity in this sample of patients treated with AHE is of the same magnitude as described in recent series of patients undergoing temporal lobe resection for medically intractable epilepsy. Likewise, affective disorders (depressive conditions) constitute the most prominent psychiatric problem after surgery for epilepsy.

[Use of psychiatric emergency clinics in Copenhagen and Frederiksberg by schizophrenic patients]. / Skizofrene patienters brug af de psykiatriske skadestuer i København og Frederiksberg.

All patients contacts at the four psychiatric emergency rooms in Copenhagen and Frederiksberg were registered every tenth day during 1985 (a total of 1969 patient contacts). Based on this material, we have compared patients who were given the diagnosis schizophrenia with other patients attending the psychiatric emergency rooms as regards demographic data, attendance patterns and treatment. There were 387 contacts from schizophrenic patients, of which 69.8% were men and 30.2% women. The schizophrenic patients were significantly younger than the other patients, and significantly more of them were unmarried, living alone and on pensions. A quarter of the schizophrenic patient contacts ended in hospital admission, either directly or after spending the night in the emergency room, 10% spent the night only, and 65% left the emergency room the same day with or without further appointments. There were signs that many of the schizophrenic patients, especially the men, used the emergency rooms as a means of human contact and a "shelter", compensating for the lack of a more personal social network. This is seen in connection with the fact that the male patients were to a greater degree without a family network. On the other hand, significantly more female schizophrenic patients were admitted to hospital or were offered overnight stays in the emergency room. Schizophrenic patients are regarded as large-scale users of psychiatric emergency rooms, which is seen in relation to recent years' limited capacity for hospital admission and lack of relevant options for housing, treatment and rehabilitation. The plans for community psychiatry in Copenhagen are expected to consider the special problems which these patients face.

[Temporal lobe epilepsy--psychiatric aspects and surgical treatment]. / Temporallapsepilepsi--psykiatriske aspekter og kirurgisk behandling.

The prevalences and types of psychiatric disorders connected with temporal lobe epilepsy and surgical treatment hereof are discussed. Studies comparing psychiatric morbidity among surgically treated patients and less selected groups of patients with epilepsy, respectively, are desired. Previous follow-up studies of patients undergoing temporal lobe resection point to a high prevalence of psychiatric disorders pre- and postoperatively, in terms of personality disturbances (especially aggression) and various psychotic disorders. On the basis of older studies, postoperative psychoses are believed to appear in 7-10% of surgically treated patients. New Brain Imaging and neurophysiological techniques permit a more precise focal diagnosis. Thus more selective surgical procedures have been introduced, e.g. resection of the amygdala and hippocampus. Together with an increased awareness of the importance of psycho-social factors and the absence of severe psychiatric disturbances for a good postoperative outcome this means that results of older studies may no longer apply. Studies reflecting present day conditions are needed.

[Psychosocial consequences and surgical treatment of epilepsy. A review]. / Psykosociale konsekvenser af epilepsi og epilepsikirurgi. En oversigt.

Epilepsy is one the commonest neurological diseases. In 25% of the cases, particularly in patients with temporal foci, the seizures prove to be resistant to medicinal treatment. Several investigations have stressed that these patients have pronounced psychosocial problems which may be more important to the patient than the actual seizures. Taking into consideration the WHO definition of health as complete physical, mental and social well-being, patients with epilepsy have problems in all of these dimensions. The major problems are social isolation and employment. Surgical treatment of epilepsy has a pronounced effect on the seizures in 90% of the operations in the best series but it is still uncertain whether reduction in the number of seizures also implies better quality of life. The present data suggest improvement in the psychosocial conditions of the patients who functioned best preoperatively and who became seizure-free after operation. The importance of further longitudinal studies emphasizing the psychosocial aspects is stressed.

[Alcohol abusers in the psychiatric emergency departments in Copenhagen and Frederiksberg]. / Alkoholmisbrugere ved de psykiatriske skadestuer i København og på Frederiksberg.

On the basis of a prospective random sample investigation of 611 alcohol-related visits to the four psychiatric emergency units of the City of Copenhagen, demographic variables, referral sources and dispositions of treatment are described. On every 10th day throughout 1985 all visits were registered. The distribution of all variables except age and sex deviate significantly from those of non-alcohol-related visits. Thus fewer alcoholics cohabit and more are divorced. 25% of the alcohol-related visits resulted in an overnight stay in the unit, while 10% resulted in admission to the psychiatric ward. For non-alcohol-related visits the proportions were the reverse.