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No abnormalities in magnetic resonance images were recorded in patients with posttraumatic stress disorder other than an increased incidence (50%) of a small cleft in the callosal-septal interface, a cavum of the septum pellucidum. A similar grade of cavum was obtained in 14% of normal volunteers matched for age, socioeconomic background, and military experience. The cavum is believed to have antedated the disorder and is conceived to be a neurodevelopmental aberration. The possibility that the cavum is a marker of vulnerability to stress in psychopathology is discussed.

In animal models of fetal alcohol syndrome (FAS), the hippocampus has been shown to be especially sensitive to the effects of prenatal ethanol exposure, exhibiting neuronal loss and alterations in neuritic process elaboration. We have characterized the influence of chronic prenatal ethanol treatment (CPET) on the postnatal expression of choline acetyltransferase (ChAT) in the hippocampus and the septal area that contains neurons that provide the primary cholinergic innervation to the hippocampus. On gestation days 1-22, pregnant rats were either fed an ethanol-containing liquid diet, pair-fed a calorically equivalent sucrose-containing diet, or given rat chow ad libitum. In Chow control animals, the ontogenetic progression of ChAT activity in the septal area and hippocampus was characterized by a significant period of upregulation during the 2nd and 3rd postnatal weeks, exhibiting and an approximate 5-fold increase (septal area) and 7-fold increase (hippocampus) by postnatal day 21 (P21). At P14, ethanol exposure reduced septal and hippocampal ChAT activity levels, compared with those of pair-fed offspring. ChAT activity reached control levels by P21 in ethanol-exposed pups, suggesting that the earlier decline in activity may reflect a delay in the ontogenetic upregulation. In addition, there was a trend toward increased septal and hippocampal ChAT activities at P1 and P7 in both liquid diet groups. This liquid diet-stimulated increase may mask the effects of ethanol on early postnatal ChAT expression in the septohippocampal system. The results suggest that prenatal ethanol exposure may influence factors that regulate the developmental expression of ChAT in the septohippocampal system.(ABSTRACT TRUNCATED AT 250 WORDS)

A highly NGF-secreting cell line was generated by retroviral transduction of a conditionally immortalized CNS-derived neural progenitor cell line. After transplantation to the nucleus basalis magnocellularis (NBM), the cells continue to express the NGF transgene for at least 10 weeks, producing sufficient NGF to reverse cholinergic neuron atrophy in aged rats and induce cellular hypertrophy in young rats. In cognitively impaired aged rats, transplants of the NGF-secreting cells placed either in the NBM and septum or in only the NBM induced a near-complete reversal of the spatial learning impairment. This was accompanied by a normalization of the size of the cholinergic neurons in the grafted areas. The results demonstrate that locally increased supply of NGF to the basal forebrain cholinergic nuclei has a significant impact on cognitive function and support the usefulness of neural progenitor cells for a long-term localized delivery of neurotrophins to the CNS.

A septum pellucidum cyst is defined as a cystic structure between the lateral ventricles, whose walls exhibit lateral bowing and are 10 mm apart or greater. This communication presents computerized tomography (CT) and magnetic resonance imaging (MRI) findings in six patients with septum pellucidum cysts, ages ranging from 1.5 to 47 yrs. The width of the cysts ranged from 13 to 23 mm, and their walls were laterally bowed. Only one patient had hydrocephalus, who was surgically treated. The remaining five patients only had intermittent headaches. It appears that further studies will be required to establish satisfactory diagnostic and therapeutic criteria for symptomatic or presumably symptomatic septum pellucidum cysts.

We report a baby's development with expanding cyst of the septum pellucidum. It was detected accidentally during diagnostic evaluation of epileptic convulsions and psychomotoric retardation. The dramatic increasing of the cyst was followed by cranial ultrasonography for ten months. The progression of clinical symptoms couldn't be explained because after drainage of the cyst, no improvement took place. MRT with Spectroscopy lead to the tentative diagnosis, Morbus Alexander. This couldn't be proved because no biopsy of the brain was performed against the decision of the child's mother, nor postmortal (the child died at 20 months).

We report a case of sudden unexpected death in an individual with epilepsy. Autopsy revealed a subependymal giant cell astrocytoma of the septum pellucidum, but there were no other lesions of tuberous sclerosis. We discuss sudden death in epilepsy, deaths related to primary brain tumors, the pathology of subependymal giant cell astrocytoma, and whether or not such a tumor can exist outside the setting of tuberous sclerosis. We also discuss the implications such findings may have on surviving family members, as well as the important role of the forensic pathologist in such cases.

Degeneration of cholinergic neurons in the basal forebrain (CBF) is a prominent neuropathological feature of Alzheimer's disease and is thought responsible for some cognitive deficits seen in patients. An animal model of pure CBF degeneration would be valuable for analysis of the function of these neurons and testing therapeutic strategies. CBF neurons express receptors for nerve growth factor. In order to selectively destroy these neurons, we developed an immunotoxin using monoclonal antibody (192 IgG) to rat NGF receptor (p75NGFr) armed with the ribosome inactivating protein, saporin. In vitro 192-saporin was highly toxic to neurons expressing p75NGFr. Intraventricular injections of 192-saporin destroyed the CBF and impaired passive avoidance learning. These results indicate that 192-saporin treated rats can be used to model a key feature of Alzheimer's disease and that anti-neuronal immunotoxins are a powerful approach to selective neural lesioning.

The use of the flexible neuroendoscope and laser fenestration in the surgical management of a symptomatic cyst of cavum septum pellucidum is reported. Successful communication was established between the cyst cavity and the lateral ventricles using this technique. Satisfactory clinical and radiological improvement as seen on MRI confirmed the operative success.

Absence of the septum pellucidum may occur as an isolated malformation. Some of the common paediatric ultrasound and radiology textbooks mention this anomaly. However, only 12 case reports have been published so far. Absent septum pellucidum is also seen in combination with other cerebral malformations like septo-optic pituitary dysplasia (SOPD, de Morsier), agenesis of corpus callosum, holoprosencephaly etc. More often it is seen as a secondary injury due to an increasing internal hydrocephalus. Occurrence of this aplasia and its significance are often underestimated. At a paediatric centre in Germany the anomaly is expected to occur in 1: 1,000 to 1:3,000 cerebral ultrasound examinations. After a review of the literature four cases are presented. All of them were observed by ultrasound during the neonatal period. Using ultrasonography diagnosis of the isolated absence of septum pellucidum can be easily performed by the experienced physician, and will usually be of eminent relevance for the patient.

DeMorsier syndrome is a well-described entity, which includes optic nerve hypoplasia and absence of the septum pellucidum with or without pituitary abnormalities. Patients with all three aspects of this syndrome are diagnosed in childhood due to their neuroendocrine dysfunction. We present a review of the literature and a case report of an adult diagnosed with DeMorsier syndrome when he developed neuroendocrine abnormalities after head trauma.

Chronic ethanol treatment induces memory deficits accompanied by anatomical and biochemical changes in basal forebrain and hippocampus. Cholinergic neurons in the septohippocampal pathway are especially vulnerable to alcohol neurotoxicity. Several studies showed that an adequate supply of neurotrophins, such as Nerve Growth Factor and Brain-Derived Neurotrophic Factor, is required for the normal function and survival of cholinergic neurons in basal forebrain and medial septal nuclei. We tested the hypothesis that chronic alcohol ingestion may alter the gene expression level of Nerve Growth Factor in hippocampus, the major source of neurotrophins to the cholinergic neurons in the septohippocampal pathway. We measured Nerve Growth Factor protein and Nerve Growth Factor mRNA contents using sensitive two-site ELISA and Northern analysis. We also tested the endogenous neurotrophic activity, including and excluding Nerve Growth Factor, contained in 5%, 2%, 1%, 0.5% and 0.1% (w/v) hippocampal tissue extracts on sympathetic ganglia neurons. Twenty-eight weeks of chronic ethanol treatment did not reduce Nerve Growth Factor protein, Nerve Growth Factor mRNA, or total neurotrophic activity contained in the rat hippocampus when measured on sympathetic ganglia neurons.

Basal forebrain cholinergic neurons atrophy and degenerate in aging and Alzheimer's disease for unknown reasons. In this study, aged male Sprague-Dawley rats (26-30 months old) showed a significant 31% reduction in the number of septal cholinergic neurons which take up and retrogradely transport 125I-labelled nerve growth factor injected into their target hippocampus, as compared with young adult rats (three to six months old). In aged rats, cholinergic neurons not transporting nerve growth factor were severely atrophied and had a significant 60% reduction in mean cross-sectional area as compared with [125I]nerve growth factor transporting neurons. These changes were accompanied by a significant 43% decline in relative levels of messenger RNA encoding the high affinity nerve growth factor receptor TrkA, in the septal region of aged rats. There was no difference between young and aged rats in messenger RNA levels encoding the low affinity nerve growth factor receptor, p75NGFR. These findings suggest that aged basal forebrain cholinergic neurons exhibit a reduced capacity to sustain receptor mediated uptake and retrograde transport of target-derived neurotrophin. This reduced capacity is associated with severe neuronal atrophy and may contribute to the pronounced vulnerability of these neurons to degeneration in aging and Alzheimer's disease.

The characteristic electroencephalographic patterns within the hippocampus are theta and sharp waves. Septal neurons are believed to play an essential role in the rhythm generation of the theta pattern. The present study examined the physiological consequences of complete and selective damage of septohippocampal cholinergic neurons on hippocampal theta activity in rats. A selective immunotoxin against nerve growth factor receptor bearing cholinergic neurons (192 immunoglobulin G-saporin), [Wiley R. G. et al. (1991) Brain Res. 562, 149-153] was infused into the medial septal area (0.11-0.42 microgram). Hippocampal electrical activity was monitored during trained wheel running, drinking and the paradoxical phase of sleep, as well as following cholinomimetic treatment. A moderate dose of toxin (0.21 microgram) eliminated the septohippocampal cholinergic projection, as evidenced by a near total absence of choline acetyltransferase-immunoreactive neurons in the medial septum and the vertical limb of the diagonal band, and by the absence of acetylcholinesterase-positive fibers in the dorsal hippocampus. In the same rats, parvalbumin immunoreactivity, a reliable marker for septohippocampal GABAergic neurons, [Freund T. F. (1989) Brain Res. 478, 375-381], remained unaltered. In addition, retrograde transport of the tracer fluorogold demonstrated that the parvalbumin cell population preserved its axonal projection to the hippocampus. Following toxin treatment, the power of hippocampal theta, but not its frequency, decreased in a dose-dependent manner. Reduction of theta power occurred between three and seven days after the toxin treatment and remained unaltered thereafter up to eight weeks. A dose which eliminated all septohippocampal cholinergic neurons (0.21 microgram) left a small but significant theta peak in the power spectra during wheel running, paradoxical phase of sleep and intraseptal infusion of carbachol (5 micrograms). Peripheral administration of physostigmine (1 mg/kg) induced only slow (1.5-2.0 Hz) rhythmic waves. No changes were observed in the gamma (50-100 Hz) band. These findings indicate that the integrity of the septohippocampal GABAergic projection is sufficient to maintain some hippocampal theta activity. We hypothesize that cholinergic neurons serve to increase the population phase-locking of septal cells and thereby regulate the magnitude of hippocampal theta.

Previous studies have demonstrated that depleting the hippocampus of endogenous neurotrophins via excitotoxic lesions fails to alter the viability of adult cholinergic septal/diagonal band neurons. Since cholinergic basal forebrain neurons may be more vulnerable during development, we investigated whether excitotoxic lesions produced in neonatal animals alter the viability of these cells. Postnatal Day 7, 10, 14, and 28 rats pups received unilateral intrahippocampal injections of ibotenic acid and were sacrificed 4 weeks later. At 7, 10, and 14 days of age, significant reductions in the number of choline acetyltransferase (ChAT)- and p75 nerve growth factor receptor (NGFr)-immunoreactive neurons were observed within the medial septum ipsilateral to the hippocampal lesion. In contrast, rats receiving similar lesions on Day 28 failed to display a significant reduction in ChAT-immunoreactive medial septal neurons. The magnitude of ChAT-immunoreactive neuronal loss within the medial septum and the age at which the lesion was made were inversely correlated (r2 = 0.887), indicating that cholinergic septal neurons become less vulnerable to target removal as the cells develop. Similar results were observed in the vertical limb of the diagonal band although a small but significant loss of ChAT-immunoreactive neurons was seen in this structure ipsilateral to the hippocampal lesion when lesions were performed on Postnatal Day 28. At all age groups, many remaining cholinergic septal/diagonal band neurons appeared dystrophic with stunted fiber outgrowth. The present study demonstrates that unlike adult rats, removal of hippocampal target neurons during development alters the viability and morphology of cholinergic neurons of the medial septum and diagonal band. This suggests that target neurons which synthesize endogenous neurotrophins are needed for normal development of cholinergic basal forebrain neurons, but may not be required for the normal maintenance of the adult cell.

The effects on anatomy and behavior of a ribosomal inactivating protein (saporin) coupled to a monoclonal antibody against the low-affinity NGF receptor (NGFr) were examined. In adult rats, NGFr is expressed predominantly in cholinergic neurons of the medial septal area (MSA), diagonal band nuclei, and nucleus basalis magnocellularis (nBM), but also in noncholinergic cerebellar Purkinje cells. Rats with immunotoxin injections to the MSA, nBM, and lateral ventricle were compared to controls on a spatial and cued reference memory task in the Morris maze. Toxin injections to the MSA slightly impaired the initial, but not asymptotic, phase of spatial navigation. Injections to the nBM impaired all phases of spatial navigation. Cued navigation, however, was not affected in either the MSA or nBM group. The ventricular injections severely affected spatial and cued navigation. Acetylcholinesterase (AChE) histochemistry and NGFr and choline acetyltransferase immunohistochemistry revealed a loss of (1) almost all NGFr-positive cholinergic neurons in the MSA and AChE fibers in hippocampus (MSA group); (2) almost all NGFr neurons in the nBM, some in the MSA, most AChE fibers in neocortex and some in the hippocampus (nBM group), and (3) almost all NGFr neurons in the MSA and nBM and their corresponding hippocampal and cortical AChE fibers (ventricular group). Cholinergic nBM projections to the amygdala were largely preserved in all groups. The amount of cholinergic fiber loss in the cortex correlated modestly, but significantly, with the severity of impairment of the asymptotic phase of performance of the spatial task. An unambiguous interpretation of the anatomical locus of behavioral deficits was not possible because of damage to cholinergic striatal interneurons (nBM group) and to noncholinergic cerebellar Purkinje cells (ventricular group). These data suggest that the cholinergic cortical system is critical to the performance of this spatial memory task. Cholinergic denervation of the hippocampus alone, however, is not sufficient to impair markedly performance of this task.

The case of a malignant intraventricular meningioma in a 6-year-old child is reported. He presented with symptoms of raised intracranial pressure and computed tomography scan revealed an enhancing tumor at the region of the septum pellucidum. After surgical excision, histology showed appearances of meningioma with atypical features indicating malignant behavior.

Holoprosencephaly is a rare brain anomaly, which may be seen in liveborn neonates, although it is more common in stillbirths and abortions. It may occur alone or as part of a large number of genetic syndromes and associations. It is thought to arise early in embryogenesis (6 weeks), as the prosencephalon is separating into the two hemispheres. It is a complex anomaly with markedly varying degrees of severity. The most severe alobar form affects the entire prosencephalon. The brain shows no evidence of division into two hemispheres. The central thalami and basal ganglia remain undivided and confluent, and there is a large, dorsally located cyst connected to the large single ventricle. These infants usually die shortly after birth. The semilobar form has variable amounts of hemispheric formation with normalization occurring from dorsal to ventral. Some posterior falx, occipital, and temporal horn formation and evidence of a third ventricle are present. It is compatible with life. The lobar form has the most nearly normal appearance. It often exhibits a well-formed ventricular system, absence of the septum pellucidum, a shallow falx, abnormal connection of gray and white matter across the midline, and partially formed frontal lobes. Facial anomalies, especially hypotelorism and midline clefts, generally parallel the brain malformation in severity. Visual and olfactory symptoms plus pituitary abnormalities are often present. Septo-optic dysplasia is a related entity. It has a constellation of symptoms of hypotelorism, severe visual problems, and short stature or other pituitary symptoms. Primary imaging findings include optic nerve hypoplasia and absent septum pellucidum. Septo-optic dysplasia somewhat resembles lobar holoprosencephaly. Septo-optic dysplasia is more common than holoprosencephaly. Isolated absence of the septum pellucidum is also thought to be a mild brain anomaly.

The effects of ibotenic acid lesion of the septum were studied in rats implanted with chronically indwelling electrodes and septal cannula. Each rat served as its own control and the properties of the hippocampal theta rhythm were studied before and after ibotenic acid and control saline infusion into the medial septal area. Ibotenic acid preferentially killed neurons in the lateral septum, and significantly attenuated the hippocampal theta rhythm about 50% bilaterally, at both surface and deep electrodes. The coherence and the phase of the theta rhythm at the CA1 apical dendrites, with respect to a superficial electrode, also declined significantly after ibotenic acid lesion. Pilocarpine (25 mg/kg i.p.) induced a theta rhythm of 7-9 Hz during immobility in the lesioned rats that was significantly higher in frequency than that induced in intact rats (4-6 Hz). In lesioned rats, the theta rhythm during tail pinch under urethane anesthesia was largely abolished, and the theta during walking was attenuated by atropine sulfate (50 mg/kg i.p.). Phencyclidine (10 mg/kg i.p.) or parachlorophenylalanine (PCPA) alone, which was inferred to abolish an atropine-resistant theta input, did not affect the power of the walking theta rhythm in either the lesioned or the normal rat. It was concluded that the theta in the behaving rats after ibotenic acid lesion in the septum has a strong atropine-sensitive component, and that it is not predominantly atropine-resistant, as suggested previously. The lack of PCPA effect on the theta phase in intact and lesioned rats also suggested a different view of the atropine-resistant theta in hippocampal region CA1. One possible mechanism of the atropine-resistant theta at the distal dendrites of pyramidal cells may result from rhythmic inhibition by stratum lacunosum-moleculare interneurons which may be activated by either serotonergic or cholinergic inputs.

A 64-year-old male presented with a unique choroid plexus metastasis from gastric cancer. Computed tomography and magnetic resonance imaging demonstrated a moderately enhanced mass in the lateral ventricle. The tumor was totally removed and histological examination revealed adenocarcinoma. Systemic investigation revealed gastric cancer. The differential diagnosis for intraventricular masses should include the possibility of metastasis from unidentified primary lesions.

A group of 159 patients with tumours in the anterior part of the third ventricle and surrounding region were analysed. According to WHO classification the tumours belong to groups I, V, VI and VII. The assessment of neurological manifestations and hormonal abnormalities makes possible their early diagnosis. CT of the head and MRI inform about the location, character and extent of the intracranial mass. Angiography provides important information on the vascularization of the tumour and its relation to the vessels of the anterior part of Willis circle and hypothalamic veins. In the surgical treatment in 37 cases microsurgery was used reducing the perioperative mortality by half. Hydrocephalus associated with the tumours was treated either by atrioventricular drainage or, when the tumour was partly removed, pellucidotomy was done. Radiotherapy was the next stage in the treatment of tumours of this location.

Five patients presented with symptoms related directly to pressure effects from their cavum septum pellucidum with persistent or intermittent obstructive hydrocephalus. The most characteristic presenting symptoms were intermittent postural headache and postural loss of consciousness. If cysts of the cavum septum pellucidum are symptomatic and stereotactic cyst puncture or fenestration are ineffective, ventriculoperitoneal shunting should be carried out before resorting to more radical excision of the cyst.

Many structural brain abnormalities have been described in schizophrenia, consistent with a neurodevelopmental model for this disease. We report here a study of the cavum septum pellucidum (CSP) in schizophrenia compared to control groups, as well as the clinical correlates of this congenital anomaly in schizophrenia. We conducted a magnetic resonance imaging (MRI) study to compare rates of CSP in schizophrenia (N = 67) v. psychiatric controls (bipolar and schizoaffective, N = 60) and healthy controls (N = 37). Of the controls 18.9%, and of all psychotic subjects 18.1% had a CSP of any size and there was no difference in the frequency of large CSP among the groups. Males had higher rates of CSP than females (25% v. 9.7%, P = 0.01) in all groups. Schizophrenics had higher CSP rates than affective patients (25%, v. 10%, P = 0.02). No clinical difference was found between schizophrenics with or without CSP.

We present an illustration of the spectrum of intracranial abnormalities associated with absence of the septum pellucidum to better define and illustrate this disorder. CT and 1.5 Tesla MRI examinations of fifteen patients with absence of the septum pellucidum were meticulously analyzed and correlated with clinical and laboratory studies. The findings were compiled and categorized based upon the presence and type of associated radiologic abnormalities. Absence of the septum pellucidum may occur as an isolated abnormality (n = 3). In most patients (n = 12), associated complex developmental abnormalities are present which include heterotopias, hypoplastic falx, ventricular clefts, encephalocele, small pituitary gland, small optic nerves and chiasm, and corpus callosal dysgenesis. Inferior pointing and a squared-off appearance of the frontal horns are frequently noted. These, or other, more severe ventricular configuration deformities are present in all patients. We have portrayed the complete range of findings associated with absence of the septum pellucidum using an illustrative approach to clarify the different patterns of radiologic abnormalities which may be seen with this complex entity.

The effect of ethanol consumption on the forebrain and hypothalamus of adult mice was investigated. A consistent decrease of biological activity and of nerve growth factor (NGF) immunoreactivity was observed in the hippocampus and hypothalamus of alcohol-treated mice. Biochemical studies also indicate that chronic ethanol intake causes a reduction in the level of choline-acetyltransferase in the septum, hippocampus and striatum, but not in the cortex and other brain regions. This study provides evidence that long-term ethanol intake causes impairment of brain NGF level and of the cholinergic enzyme, regulated by NGF, suggesting that NGF synthesis and/or biological activity is affected in alcohol-related brain neuropathology.

Subependymoma is a rare, benign intraventricular tumour and a case of septum pellucidum origin examined with CT and MR is reported. Well demarcated non-enhancing mass with multiple small intratumoral cysts is demonstrated on CT and MR images. The differential diagnosis from ependymoma has some therapeutic implications but may not be possible by CT or MRI.

We examined the effect of imaging plane and sequence on the demonstration of lesions at the callosal-septal interface (CSI) by magnetic resonance imaging in 20 patients with known multiple sclerosis. Variable-echo-(VE) T2- and proton density (PD) weighted images were performed in coronal axial and sagittal planes. Sagittal gradient echo (GE) T2- and PD-weighted images were also performed. Lesions at the CSI were seen in all patients and were all demonstrated on both sagittal and coronal VE images. Sagittal PD-weighted GE images were slightly less sensitive but showed good overall agreement with sagittal VE. Axial VE and sagittal T2-weighted GE images demonstrated CSI lesions poorly.

Computed tomography (CT) was performed in 338 active professional boxers. CT scans were abnormal in 25 boxers (7%). The most common CT abnormality was brain atrophy (22 cases). Focal lesions of low attenuation consistent with posttraumatic encephalomalacia were noted in only three boxers. Boxers with abnormal CT scans did not differ from those with borderline or normal CT scans in regard to age, win-loss record, number of bouts, or history of an abnormal electroencephalogram. Thirty-seven boxers with borderline CT scans (49%) and 17 with abnormal CT scans (68%) reported a previous technical knockout (TKO) or knockout (KO), compared with only 89 (37%) of the 238 boxers with normal CT scans (P < .01). Brain atrophy was noted more frequently in boxers with a large cavum septum pellucidum (CSP) than in those with a small or no CSP (P < .05). Boxers with abnormal or borderline CT scans who experienced a TKO or KO were slightly older than those with normal CT scans and a history of a TKO or KO (P < .05).

A 63-year-old man was admitted to our hospital because of loss of memory, disorientation, nausea, and urinary incontinence. Cerebral computed tomographic and magnetic resonance imaging scans revealed a tumor with intratumoral hemorrhage affecting the corpus callosum and the septum pellucidum. A partial resection of the tumor was performed, but the patient died the next day from an episode of bleeding. Postmortem examination revealed a highly vascularized subependymoma with acute bleeding in the tumor and in the surrounding brain parenchyma. The importance of considering a highly vascularized subependymoma is noted when a tumor related to the ventricular system is diagnosed.

A cavum septum pellucidum (CSP) has been regarded as an incidental finding of little clinical importance. However, an association between this developmental anomaly and a diagnosis of psychosis has previously been reported. We determined the prevalence of the CSP in parallel studies of brain scans obtained with magnetic resonance (MR) imaging and in the post-mortem brains of schizophrenic patients compared with normal controls. We found a significantly increased prevalence of the CSP in both the MR scans and post-mortem brains of schizophrenic patients compared with controls. In the MR study, 17 of 81 (21%) schizophrenic patients but only 1 of 46 (2%) control subjects had a CSP. In the post-mortem study, 17 of 28 (61%) schizophrenic patients and 12 of 39 (31%) normal controls had a CSP. The increased prevalence of a CSP in schizophrenic patients further indicates that anomalous development of the limbic system is an important aspect of this disorder.

Insulin and insulin-like growth factors I and II (IGF-I and IGF-II) have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action in the brain are unknown. Since central neurons are particularly vulnerable to hypoglycemia that results from ischemia or other insults, we tested the hypothesis that growth factors can protect central neurons against hypoglycemic damage in vitro. IGF-I and IGF-II (3-100 ng/ml) each prevented glucose deprivation-induced neuronal damage in a dose-dependent manner in rat hippocampal and septal cell cultures. High concentrations of insulin (greater than 1 microgram/ml) also protected neurons against hypoglycemic damage. Epidermal growth factor did not protect against hypoglycemic damage. Both IGFs and insulin were effective when administered 24 hr before or immediately following the onset of glucose deprivation. Direct measurements of intraneuronal calcium levels and manipulations of calcium influx demonstrated that calcium influx and sustained elevations in intraneuronal calcium levels mediated the hypoglycemic damage. IGF-I and IGF-II each prevented the hypoglycemia-induced elevations of intraneuronal free calcium. Studies with excitatory amino acid receptor antagonists and calcium channel blockers indicated that NMDA receptors did, and L-type calcium channels did not, play a major role in hypoglycemic damage. Taken together, these findings indicate that IGFs can stabilize neuronal calcium homeostasis and thereby protect against hypoglycemic damage.

An uncommon association of infantile spasms, septo-optic dysplasia, partial agenesis of the corpus callosum and an interhemispheric cyst is described in a child. The combination of these findings has not, to our knowledge, been previously reported.

Age-related changes in the cholinergic cells have been reported in the rat medial septal area. The neuropeptide galanin is colocalized with acetylcholine in the majority of the medial septal neurons. To assess possible age-related changes in the galanin-containing septal cells, we have examined, with immunohistochemical methods, the distribution pattern, density, and morphological features of galanin-containing cells in the rat medial septal nucleus (MS) and the nucleus of the diagonal band of Broca (DBB) in 1, 3-6, 9-12, 16-18, 24-27, and 28-30 month-old rats. A morphometric computerized analysis was also performed. In addition, the intensity of the immunolabelling was measured by densitometry. Galanin-like immunoreactivity (galanin-LI) was present in both the MS and the DBB. Our results clearly indicate a progressive age-related decrease in the number of galanin-positive cells throughout the MS-DBB complex. Our quantitative study revealed a significant loss of galanin-positive cells in the MS-DBB complex of 16-18 (50.4%), 24-27 (52.3%), and 28-30 (52.4%) month-old rats compared to 3-6 month-old animals. A non-significant reduction (28.6%) in galanin-LI cell number was observed in 3-6 month-old rats compared to 1 month-old animals. The morphometric analysis demonstrated a significant reduction (18%) in the surface of galanin-positive cells remaining in the 28-30 month-old group. Furthermore, a significant decrease in the immunolabelling intensity was consistently observed in animals of 16 month-old and older. To determine whether changes in galanin-positive cells were associated with cholinergic changes, the number of cells stained for acetylcholinesterase (AChE) was estimated in 3-6, 9-12, 16-18, and 24-27 month-old rats. There was a 43% decrease in the number of AChE-positive cells and a 71% loss of galanin-positive cells in 24-27 month-old rats compared to 3-6 month-old. The galanin-cell loss in the medial septal area was therefore associated with a parallel, although smaller, cholinergic septal cell loss.

Idiopathic chronic autonomic dysfunction may occur as pure autonomic failure (PAF) or in association with multiple system atrophy (MSA). CSF immunoreactivity to rat locus ceruleus occurred in a significantly greater number of samples from MSA patients compared to control subjects or patients with PAF. Other brain regions infrequently showed immunoreactivity. These findings suggest that degeneration in MSA may release antigen(s) that induce antibodies against locus ceruleus neurons. Further studies are required to determine whether immune abnormalities play a pathogenetic role in MSA. Lack of CSF immunoreactivity in PAF is consistent with primarily peripheral involvement.

The lateral septal area (LSA) has been implicated in the control of various psychoneuroendocrine processes in the rat. Interactions between the endocrine and immune systems and sex differences in immunity reflect the interdependence of the immune and neuroendocrine systems. Kainic acid (KA) lesions in the lateral septal area not only modify neuroendocrine processes, but also produce a suppression of humoral immunity in female rats. Presently, we have evaluated the effects of neurotoxic lesions in the LSA on the humoral immune response and body weight regulation of male and female rats. Bilateral lesions in the LSA of adult male and female rats were produced by stereotaxically infusing either 0.25 microliters of kainic acid (1.5 micrograms/microliters) or 0.5 microliters of domoic acid (DA; 0.3 micrograms/microliters) into the LSA. In an additional study, LSA lesions using 0.25 microliters of DA (0.6 micrograms/microliters) were produced in female rats only. Sham operations consisted of bilateral injections of 0.9% saline into the LSA. The effects of these lesions on antibody production, following immunization with 100 micrograms ovalbumin in complete Freund's adjuvant, were examined. Blood samples were collected on Days 7 and 14 following immunization. The anti-ovalbumin IgM and IgG antibody titers were measured by an enzyme amplified ELISA assay. As found previously, KA-induced LSA lesions in adult female rats produced an increase in body weight and a suppression of the humoral immune response. However, LSA lesions produced with the neurotoxin DA had a similar effect on body weight but had no effect on humoral immunity. In male rats, neither body weight regulation nor the humoral immune response was affected by KA or DA lesions in the LSA. These results indicate that the effects of neurotoxic LSA lesions on body weight regulation and the humoral immune response are sex specific and further demonstrate that two closely related kainate neurotoxins have differential effects on the humoral immune response, but have similar effects on body weight regulation. Thus, neurons in the LSA of female rats that are involved in the inhibitory control of body weight are susceptible to both KA and DA, whereas neurons in the LSA associated with immunoregulation are differentially affected by KA and DA. Of further interest, a sex difference in DA susceptibility was noted, with male rats showing greater cell loss in the LSA following DA infusions, as compared to female rats.

Spontaneous alternation which is disrupted by lesion of septal dopaminergic (DA) afferents was chosen as a behavioral marker for the study of functional interactions between DA and noradrenergic (NA) innervation of the lateral septum. Three groups of rats were studied: a solvent group which received only vehicle injection, and two lesioned groups, one with DA lesion and the second with simultaneous DA + NA lesion of the septal innervation. DA lesion was produced by infusing 6-hydroxydopamine (6-OHDA) into the lateral septum after pretreatment with desmethylimipramine (DMI) injected intraperitoneally. The DA + NA lesion was produced by infusing 6-OHDA without DMI pretreatment. The lesion of DA innervation alone led to a disturbance of alternation behavior in a Y-maze, but performance was not affected by the combined DA + NA lesion. The group with septal DA lesion was then injected with 6-OHDA into the pedunculus cerebellaris superior (PCS) in order to destroy NA efferents from the locus coeruleus. The two other groups were sham-operated. After post-operative recovery, the rats were retested for spontaneous alternation. The rats with the PCS NA lesion subsequent to the DA septal lesion displayed normal alternation behavior. Their performance was not different from that of animals with both NA and DA lesions in the septum. Thus the NA lesion appears to prevent the alternation deficits induced by the DA septal lesion, and also abolishes the deficits induced by the prior DA lesions. These results may have therapeutic implications.

The HT4 cell line was derived from infection of a mouse neuroblastoma cell line with a retrovirus that encoded the temperature-sensitive (ts) mutant of SV40 large T antigen. At nonpermissive temperature, HT4 cells differentiated with neuronal morphology, expressed neuronal antigens, synthesized nerve growth factor (NGF) mRNA, and secreted biologically active NGF in vitro. We sought to establish whether transplanted HT4 cells expressed class I major histocompatibility complex (MHC) antigens, a partial requirement for recognition by cytotoxic T lymphocytes (CTL), and thus be susceptible to xenograft rejection. Differentiated HT4 cells expressed marginally detectable levels of class I MHC antigens, but demonstrated higher levels of class I MHC expression after treatment with interferon-gamma. However, HT4 cells were resistant to direct lysis by perforin, the pore-forming protein of CTLs, and thus may have potential use in xenograft experiments. To address whether HT4 cells secrete NGF in vivo, HT4 cells were transplanted into adults rats with unilateral fimbria-fornix transections. A ts cell line derived from P4 cerebellum, BT1, that does not differentiate with neuronal phenotype or synthesize NGF in vitro, was transplanted as a control. Six weeks posttransplant. HT4 cells had integrated into host CNS without forming tumors. In BT1 transplants, the number of medial septal acetylcholinesterase (AChE)-positive cells was reduced to 26-39% of the contralateral control side, depending on the rostrocaudal level. In HT4 transplants, the number of cholinergic septal neurons was 58-78% of the contralateral side. This percentage was significantly (P less than 0.005) greater than that seen with BT1 transplants, indicating that transplanted HT4 cells secrete NGF in vivo and rescue cholinergic septal neurons following fimbria-fornix transection.

A rare case of an abscess in the cavum septi pellucidi (CSP) is described and previously reported cases are reviewed. A 60-year-old male was admitted to the hospital because a diagnosis of cerebellar hemisphere infarction was made on CT scan. Seven years earlier, the patient had undergone a craniotomy for aneurysm clipping, and a ventriculo-peritoneal shunt was installed for normal pressure hydrocephalus 14 days after the aneurysmal rupture. On his second hospitalization CT scan also demonstrated CSP but this was not associated with ventriculomegaly. He was placed on a rehabilitation regimen and his hospital course was uneventful. Two months later, however, he developed hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone. After analysis of CSF obtained from the shunting device, a diagnosis of meningitis was made and CSF culture revealed E. coli infection. A part of the peritoneal tubing was torn and missing when the tube was removed from the peritoneal cavity and converted to outer drainage. Being treated with intrathecal and intravenous antibiotics administration, the meningitis subsided. However, CT scan taken twelve days after the onset of the infection showed an abscess in CSP which showed ring enhancement after contrast media. Therefore, the patient continued to receive intravenous antibiotics to counter the mass effect due to the abscess. The abscess had disappeared on follow-up CT scan obtained ten days later. The patient, however, eventually expired after iatrogenic hypernatremia associated with acute renal failure. The patient was submitted to an autopsy. The authors speculate that the abscess developed through a retrograde cisternal route after infection which had originated from bowel perforation by the peritoneal shunt tube.

A wide cavum septum pellucidum defined as a separation of greater than 1 cm of the leaves occurs uncommonly. Nine children with wide cavum septum pellucidum were studied; 8 were abnormal. Observed abnormalities included cognitive impairment (8), seizures (4), hypoplasia of the corpus callosum (4), optic nerve hypoplasia (2), and growth failure (4). The incidence of intellectual dysfunction, the association with midline anomalies of the brain, and growth failure all suggest that wide cavum septum pellucidum may represent part of a spectrum of midline brain anomalies.

Following a unilateral fimbria-fornix lesion, the delivery of nerve growth factor (NGF) to the ipsilateral lateral ventricle of the rat can prevent the lesion-induced loss of choline acetyltransferase (ChAT) expression in the ipsilateral medial septum and vertical diagonal band region. In the present study, the ability of polymer rods to deliver NGF and to prevent a decrease in basal forebrain ChAT expression following a fimbria-fornix lesion was assessed. NGF was loaded into an ethylene vinyl acetate copolymer (EVAc) rod, fabricated by a melt-extrusion process. NGF release was established by the ability of the rods to induce neurite extension from PC12 cells and chick E12 dorsal root ganglia. Unilateral aspirative lesions of the fimbria-fornix were performed in adult rats, followed by implantation of a polymer rod into the ipsilateral lateral ventricle. Five animals received EVAc rods containing only the carrier molecule bovine serum albumin (BSA), and six received EVAc rods containing both BSA and NGF. After 2 weeks, ChAT-positive cells were counted in the medial septum and vertical diagonal band regions. Rats with NGF-releasing rods displayed ChAT(+) cell counts ipsilateral to the lesion equal to 88% of those on the contralateral side. In contrast, ChAT(+) cell numbers were 42% in animals with rods releasing BSA only (P less than 0.001). No undue reaction to implanted rods was noted. Following a fimbria-fornix lesion, NGF released from polymer matrices effectively prevents a lesion-induced reduction in ChAT expression in basal forebrain neurons.

Nerve growth factor (NGF), a neurotrophic factor acting on cholinergic neurons of the basal forebrain, has been proposed as a treatment for Alzheimer's disease. Experimental support for its pharmacological use is derived from short-term studies showing that intraventricular administration of NGF during 2-4 weeks protects cholinergic cell bodies from lesion-induced degeneration, stimulates synthesis of choline acetyltransferase, and improves various behavioral impairments. To investigate the consequences of long-term NGF administration, we tested whether cholinergic cell bodies are protected from lesion-induced degeneration and whether cholinergic axons are stimulated to regrow into the denervated hippocampus following fimbrial transections. We found that intraventricular injections of NGF twice a week for 5 months to adult rats resulted in extended protection of cholinergic cell bodies from lesion-induced degeneration and did not produce obvious detrimental effects on the animals. NGF treatment mildly stimulated growth of cholinergic neurites within the 2-mm area directly adjacent to the fimbrial lesion but it failed to induce significant homotypic growth of cholinergic neurites into the deafferented hippocampus.

The clinical and histopathological features of 19 patients with tumors involving the septum pellucidum are presented. These tumors predominantly affected young adults, and the clinical manifestations were usually the results of raised intracranial pressure related to obstructive hydrocephalus, mental abnormality, epileptic seizures, or a combination of these. Seventeen of the tumors grew mainly in the lateral and third ventricles, and the other 2 grew both into the lateral ventricle and the cerebral parenchyma. The direction of cellular differentiation of the tumor cells varied from patient to patient and consisted of 8 neurocytomas, 1 mature neuronal tumor with ganglionic and small round neuronal cells, 3 subependymomas, 3 subependymal giant cell astrocytomas, 2 pilocytic astrocytomas, 1 malignant astrocytoma, and 1 teratoma with embryonal carcinoma. These tumors were considered to have arisen from the multipotential cells in the subependymal plate or germ cell rests in the lateral ventricular wall, especially in the septum pellucidum. Because of the relatively inert biological behavior and histological features of most of these tumors, we favor the malformative theory of their origin. Either total or an extensive excision of the tumors in this series, which had developed mainly in the ventricular system, provided long-term survival in many cases.

Fenestrations of the septum pellucidum may be noted in hydrocephalic infants. This finding and its changing image was noted in six premature infants evaluated by neurosonography over time periods ranging from weeks to months. Breaks in the septum were noted to occur from 14 days to 23 weeks after the sonographic diagnosis of hydrocephalus. Some of these fenestrations were noted to increase in size and/or become bilateral over time. The awareness of evolving fenestrations and their late-stage images helps avoid confusion with partial and complete agenesis of the septum pellucidum and their possible associated neuroanatomical abnormalities.