It does Exist! Traumatic Hemorrhage in Septum Pellucidum.

Although bleeding into the septum pellucidum often occurs in the presence of a tumour, trauma-induced septal pellucidum hemorrhage has not been reported yet, as far as the current literature is concerned. The absence of hemorrhage on the first post-trauma imaging of the patient but the presence of hemorrhage in the brain tomography taken 12 hours later reveals the existence of trauma-induced septum pellucidum hemorrhage. Key Words: Head trauma, Brain injury, Septum pellucidum, Hemorrhage.

[An Uncommon Cerebral Lesion in Computed Tomography]. / Ungewöhnliche zerebrale Läsion in der Computertomografie.

We report the case of a 84-year-old man who suffered a hematoma of the septum pellucidum due to a fall. The development of the septum pellucidum and its implications on pathomechanisms in head injury are discussed. In the setting of trauma, a reliable differentiation to other septal lesions can be impossible in computed tomography alone, unless earlier examinations are availabe for comparison. Additional magnetic resonance imaging may be warranted in case of vicinity of the lesion to the interventricular foramina.

Some observations on the septum pellucidum.

The thin, vertically placed partition consisting of two laminae separated by a narrow chink constitutes the cavity of the septum pellucidum, known from the time of Sylvius. Traumatic lesions in boxers, rare congenital expanding cysts causing hydrocephalus, and a number of septo-optic dysplasias give clinical significance to the septum and its related cavum.

Development of a cavum septi pellucidi after Ommaya reservoir placement: report of an unusual complication.

Objective and importance. We present a complication of Ommaya reservoir placement that has not been previously reported. Following injection of a seemingly appropriately placed catheter, the patient developed seizures. Imaging studies showed the development and resolution of a cavum septi pellucidi. This case illustrates that the septum pellucidum is made of two layers and that a potential space exists between these layers. Caution is recommended when injecting a single-hole ventricular catheter if the tip is against the septum pellucidum.

The influence of septal lesions on sodium and water retention induced by Walker 256 tumor.

In the course of studies on the effects of septal area lesions on neuroimmunomodulation and Walker 256 tumor development, it was observed that tumor-induced sodium and water retention was less marked in lesioned than in non-lesioned rats. In the present study possible mechanisms involved in this phenomenon were investigated. The experiments were performed in septal-lesioned (LW; N = 15) and sham-operated (SW; N = 7) 8-week-old male Wistar rats, which received multifocal simultaneous subcutaneous (sc) inoculations of Walker 256 tumor cells about 30 days after the stereotaxic surgery. Control groups (no tumor, sham-operated food-restricted (SFR), N = 7) and lesioned food-restricted (LFR, N = 10) were subjected to a feeding pattern similar to that observed in tumor-bearing animals. Multifocal inoculation of Walker 256 tumor rapidly induces anorexia, which is paradoxically accompanied by an increase in body weight, as a result of renal Na+ and fluid retention. These effects of the tumor were also seen in LW rats, although the rise in fractional sodium balance during the early clinical period was significantly smaller than in SW rats (day 4: SW = 47.6 +/- 6.4% and LW = 13.8 +/- 5.2%; day 5: SW = 57.5 +/- 3.5% and LW = 25.7 +/- 4.8%; day 6: SW = 54.4 +/- 3.8% and LW = 32.1 +/- 4.4%; P < 0.05), suggesting a temporary reduction in tumor-induced sodium retention. In contrast, urine output was significantly reduced in SW rats and increased in LW rats (LW up to -0.85 and SW up to 4.5 ml/100 g body weight), with no change in osmolar excretion. These temporary changes in the tumor's effects on LW rats may reflect a "reversal" of the secondary central antidiuretic response induced by the tumor (from antidiuretic to diuretic).

The influence of septal lesions on sodium and water retention induced by Walker 256 tumor

In the course of studies on the effects of septal area lesions on neuroimmunomodulation and Walker 256 tumor development, it was observed that tumor-induced sodium and water retention was less marked in lesioned than in non-lesioned rats. In the present study possible mechanisms involved in this phenomenon were investigated. The experiments were performed in septal-lesioned (LW; N = 15) and sham-operated (SW; N = 7) 8-week-old male Wistar rats, which received multifocal simultaneous subcutaneous (sc) inoculations of Walker 256 tumor cells about 30 days after the stereotaxic surgery. Control groups (no tumor, sham-operated food-restricted (SFR), N = 7) and lesioned food-restricted (LFR, N = 10) were subjected to a feeding pattern similar to that observed in tumor-bearing animals. Multifocal inoculation of Walker 256 tumor rapidly induces anorexia, which is paradoxically accompanied by an increase in body weight, as a result of renal Na+ and fluid retention. These effects of the tumor were also seen in LW rats, although the rise in fractional sodium balance during the early clinical period was significantly smaller than in SW rats (day 4: SW = 47.6 = 6.4 percent and LW = 13.8 = 5.2 percent; day 5: SW = 57.5 = 3.5 percent and LW = 25.7 = 4.8 percent; day 6: SW = 54.4 = 3.8 percent and LW = 32.1 = 4.4 percent; P<0.05), suggesting a temporary reduction in tumor-induced sodium retention. In contrast, urine output was significantly reduced in SW rats and increased in LW rats (LW up to -0.85 and SW up to 4.5 ml/100 g body weight), with no change in osmolar excretion. These temporary changes in the tumor's effects on LW rats may reflect a "reversal" of the secondary central antidiuretic response induced by the tumor (from antidiuretic to diuretic)

[Genetic expression of nerve growth factor in the central nervous system. Evaluation of an experimental model for Alzheimer's dementia]. / Expresión genética del factor de crecimiento neural en el sistema nervioso central. Evaluación en un modelo experimental de demencia de Alzheimer.

INTRODUCTION AND OBJECTIVE: Several authors have suggested that loss of neuronal trophic support may be an important element in the physiopathology of degenerative conditions of the central nervous system such as Alzheimer's dementia, Parkinson's disease or amyotrophic lateral sclerosis amongst others. In the light of present knowledge, the survival of cholinergic populations of the anterior basal cerebrum, closely involved with cognitive processes of memory and learning, is associated with adequate function of the neural growth factor (NGF). These populations are markedly damaged in Alzheimer's disease, and this has been correlated with the progressive loss of memory and intellectual involvement seen in this disorder. The model used in this study was based on section of the septohippocampal connecting pathways, so that transport of regulatory impulses from the hippocampus to the medial septum was interrupted. This has lethal results for the cholinergic neurons of the latter. We have developed a study designed to characterize the expression of the gene of NGF in different regions of the brain, involved in cholinergic neurotransmission in healthy and in damaged tissue. MATERIAL AND METHODS: We used a molecular hybridization technique with a cDNA catheter complementary to the radio-isotope marked NGF human gene. RESULTS AND CONCLUSIONS: The highest levels of expression were found in the healthy cortex and hippocampus. The reduction in the levels of mRNA of NGF in the damaged hippocampus supports the current thesis which considers synaptic activity to be a major regulator of the synthesis of this molecule in the brain.

Behavioral characterization of metrifonate-improved acquisition of spatial information in medial septum-lesioned rats.

We investigated the effects of acute oral pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation in medial septum-lesioned rats. We observed that metrifonate (30 mg/kg, orally) (1) does not alter the pattern of exploration of lesioned rats at the water maze pool or retrieval of spatial memory, (2) effectively reverses the acquisition defect, (3) enhances reversal learning, and (4) improves acquisition of water maze navigation by facilitating the encoding of the spatial representation of a specific environment. These results indicate that metrifonate does not improve escape performance to the hidden platform by modulating exploration strategy, but that metrifonate enhances the speed and accuracy of development and durability of spatial memory engrams, and facilitates learning capacity that depends on activity of the septo-hippocampal projection.

Neurotrophin-4/5 maintains the cholinergic phenotype of axotomized septal neurons.

We examined the effect of intraseptal or intracerebroventricular (i.c. v.) infusions of NT-4/5 or intraseptal infusions of NGF on the level of immunohistochemical staining of choline acetyltransferase (ChAT)and the low-affinity nerve growth factor receptor (LNGFR)in the rat medial septum following unilateral transection of the fimbria. The extent of cell loss in the septum ipsilateral to the lesion, determined by cell counts of ChAT-immunopositive neurons and expressed as a ratio comparing the lesioned to the intact sides, was 0.28 in animals that received an infusion of phosphate-buffered saline (PBS). The ratios were 0.97 and 1.07 in animals that received an infusion of NT-4/5 into the ipsilateral ventricle and septum respectively. Septal infusions of NGF produced a ratio of ChAT-immunopositive cells of 1.03. The ratios of LNGFR-immunopositive neurons increased from 0.50 in PBS-infused animals to 0.79 and 0.83 in animals infused with NT-4/5 via the i.c. v. infusion of NT-4/5 or septal infusion of NT-4/5 or NGF. As determined by immunohistochemical staining, NT-4/5 infused into the lateral ventricle was detected in the periventricular portions of the forebrain ipsilateral to the infusion, while NT-4/5 or NGF infused intraseptally was detected in much of the septum, bilaterally. Furthermore, exogenous NT-4/5 or NGF was detected in numerous neuronal perikarya in the medial septal and diagonal band nuclei. These data demonstrate that, as with NGF, i.c.v. as well as septal infusions of NT-4/5 can maintain the phenotype of basal forebrain cholinergic neurons following axotomy.

Maintaining the neuronal phenotype after injury in the adult CNS. Neurotrophic factors, axonal growth substrates, and gene therapy.

Multiple genetic and epigenetic events determine neuronal phenotype during nervous system development. After the mature mammalian neuronal phenotype has been determined it is usually static for the remainder of life, unless an injury or degenerative event occurs. Injured neurons may suffer one of three potential fates: death, persistent atrophy, or recovery. The ability of an injured adult neuron to recover from injury in adulthood may be determined by events that also influence neuronal phenotype during development, including expression of growth-related genes and responsiveness to survival and growth signals in the environment. The latter signals include neurotrophic factors and substrate molecules that promote neurite growth. Several adult CNS regions exhibit neurotrophic-factor responsiveness, including the basal forebrain, entorhinal cortex, hippocampus, thalamus, brainstem, and spinal cord. The specificity of neurotrophic-factor responsiveness in these regions parallels patterns observed during development. In addition, neurons of several CNS regions extend neurites after injury when presented with growth-promoting substrates. When both neurotrophic factors and growth-promoting substrates are provided to adult rats that have undergone bilateral fimbria-fornix lesions, then partial morphological and behavioral recovery can be induced. Gene therapy is one useful tool for providing these substances. Thus, the mature CNS remains robustly responsive to signals that shape nervous system development, and is highly plastic when stimulated by appropriate cues.

Increased glucocorticoid receptor gene expression in the rat hippocampus following combined serotonergic and medial septal cholinergic lesions.

Glucocorticoid excess is associated with hippocampal neuronal dysfunction and loss, mainly affecting CA1. Degeneration of both cholinergic and serotonergic (5-HT) hippocampal afferents is prominent in aged rats and Alzheimer's disease. Lesions of these individual pathways alter hippocampal expression of mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNAs; both transcripts are increased by cholinergic lesions, but markedly decreased by serotonergic denervation. In the present study we found that combined medial septal cholinergic and central 5-HT lesions increase hippocampal GR mRNA expression, specifically in CA1 and CA2 subfields, whereas MR mRNA expression was similar to controls. Thus the effects of the cholinergic lesion, at least upon GR gene expression, appear to predominate while the effects of the lesions upon MR gene expression were additive. Increased hippocampal GR gene expression per neuron may increase hippocampal neuronal vulnerability with age or disease.

Changes in CCK mRNA in hippocampal neurones following fimbria fornix transection.

Preprocholecystokinin (CCK) mRNA expression was measured in a subset of hippocampal interneurones after transection of afferent septohippocampal fibres in the fimbria fornix. Two weeks after the lesions were made, CCK mRNA levels were significantly lower in these neurones on the side ipsilateral to the lesion compared with equivalent neurones on the unlesioned side. These findings suggest that axotomizing lesions can change gene expression in denervated target cells, and that CCK mRNA levels in hippocampal interneurones may be modulated by afferent septohippocampal input.

[Traumatic intraventricular hemorrhage in severe head injury].

Among 329 cases with comatose state caused by severe head injury, 32 had primary intraventricular hemorrhage as revealed on initial CT scan (13.4%). We divided traumatic intraventricular hemorrhage into 4 types. Type 1: massive hemorrhage (9 cases). Type 2: subependymal hemorrhage (8 cases). Type 3: damage of fornix or septum pellucidum (8 cases). Type 4: Nieveau (7 cases). Most of these cases were caused by traffic accident. Shearing injury may be the most accurate mechanism to produce the intraventricular hemorrhage. Shear strain in severe head injury should cause tears of the subependymal vein, fornix, septum pellucidum and choroid plexus. 8 cases out of 32 ventricular hemorrhage showed tear of the subependymal vein. 8 of our cases showed damage of the fornix of septum pellucidum. These results suggested that the anatomical structure of the fornix and septum pellucidum were weak points for shearing force. 20 cases in 32 with ventricular hemorrhage died. These cases were frequently associated with other traumatic lesions, namely contusion of white matter and grey matter, brain stem lesions and cerebellar contusion, caused by shearing injury. Therefore, the prognosis of severe head injury with intraventricular hemorrhage is poor.

[The influence of damage to the septum pellucidum on the effects of electrical stimulation of the hypothalamus in rabbits]. / Vliianie povrezhdeniia prozrachnoi peregorodki na éffekty élektricheskoi stimuliatsii gipotalamusa u krolikov.

In chronic experiments the influences of septal lesions on the behavioural emotional effects of electrical stimulation of various hypothalamic nuclei were investigated. The total ablation of the septum caused irreversible increase of the lateral hypothalamus self-stimulation and reversal of the negative emotional responses (escape--avoidance) to the medial hypothalamus stimulation into the positive self-stimulation behaviour. When the septal ablation was only partial, involving mainly the medial nucleus, effects were weaker and lasted only 2-3 days after the surgery. The role of the septum in the septohippocampal behavioural inhibition system (J. Gray) is discussed.

Effect of recombinant human nerve growth factor on presynaptic cholinergic function in rat hippocampal slices following partial septohippocampal lesions: measures of [3H]acetylcholine synthesis, [3H]acetylcholine release and choline acetyltransferase activity.

To determine whether intraventricular administration of nerve growth factor alters presynaptic cholinergic function in the intact hippocampus or following partial lesions of the fimbria, we investigated the effects of recombinant human nerve growth factor treatment on [3H]acetylcholine synthesis and release by hippocampal slices following various treatment regimens. For chronic nerve growth factor treatment, 1 microgram of recombinant human nerve growth factor was injected intraventricularly every second day. Lesions reduced [3H]acetylcholine synthesis (by 48%) and spontaneous and evoked [3H]acetylcholine release by 35 and 61%, respectively. Chronic nerve growth factor treatment over three weeks elevated [3H]acetylcholine synthesis (by 39%) and spontaneous and evoked [3H]acetylcholine release by 27 and 64%, respectively, over values in lesioned hippocampi of animals treated with a control protein (cytochrome c). The nerve growth factor-induced enhancement of presynaptic cholinergic function persisted for three weeks following the termination of nerve growth factor administration. Furthermore, chronic (nine-week) treatment with nerve growth factor increased [3H]acetylcholine by 118% over values in lesioned hippocampi of animals treated with cytochrome c. These findings indicate that chronic treatment with recombinant human nerve growth factor increases the capacity of hippocampal cholinergic neurons surviving a partial fimbrial transection to synthesize, store and release acetylcholine. Application of recombinant human nerve growth factor during the initial weeks after lesioning was necessary to product significant elevations in acetylcholine synthesis, since chronic recombinant human nerve growth factor treatment after delays of three or more weeks were ineffective. Furthermore, chronic nerve growth factor treatment failed to stimulate acetylcholine synthesis and release in intact hippocampal cholinergic systems. Single intraventricular injections of recombinant human nerve growth factor at the time of lesioning resulted in a small decrease in acetylcholine synthesis which, however, was not accompanied by a change in the rate of evoked acetylcholine release from cholinergic neurons surviving the lesion. The study indicates that chronic or repeated administration of nerve growth factor during the onset of degenerative events is necessary for the stimulation of presynaptic cholinergic function in the hippocampus of adult rats with partial fimbrial transections.

Graft-induced behavioral recovery from subcallosal septohippocampal damage in rats depends on maturity stage of donor tissue.

Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, 10-14 days later, received intrahippocampal suspension grafts of septal-diagonal band tissue from either 14-day-old (Group S14, n = 8) or 16-day-old fetuses (Group S16, n = 10), or of parietal cortex from 16-day-old fetuses (Group Cx, n = 10). Sham-operated (Group S, n = 10) and lesion-only (Group Fifo, n = 21) rats served as non-grafted controls. Spontaneous alternation was assessed in a T-maze at three weeks and two months post-grafting. Home cage and open field activity as well as radial maze learning were assessed from two months post-grafting onwards. Fimbria-fornix lesions induced lasting hyperactivity in both the open field and the home cage, impaired radial maze learning and transiently reduced spontaneous alternation rates. Neither type of graft significantly affected home cage activity. Septal-diagonal band grafts improved open field habituation (within trial decline of ambulatory activity) and radial maze learning; the former was observed only in S16 rats, whereas the latter was observed only in S14 rats. Acetylcholinesterase histochemistry revealed an initial lesion-induced depletion of hippocampal acetylcholinesterase (eight days post-surgery) which was no longer observed at the end of the experiment. Acetylcholinesterase positivity was similar in S14 and S16 grafts, which also contained many choline acetyltransferase-positive neurons. Cortical grafts were found to be almost devoid of acetylcholinesterase positivity and no well-stained choline acetyltransferase-positive neurons could be identified. Septal-diagonal band grafts from 14-day-old fetuses and cortical grafts contained more parvalbumin-positive neurons than septal-diagonal band grafts provided by 16-day-old fetuses. These results suggest that grafts rich in cholinergic neurons may promote behavioral recovery from fimbria-fornix lesion-induced deficits. However, such a recovery may concern different behavioral deficits as a function of the age of the implanted tissue, suggesting that the maturity stage of the donor may critically influence the functional expression in the lesioned recipient. Also, such a recovery does not appear to be related solely to cholinergic hippocampal (re)innervation and might depend on the presence, not only of cholinergic neurons, but also of non-cholinergic neuronal populations, such as parvalbumin-positive (probably GABAergic) neurons.

Nerve growth factor treatment after brain injury prevents neuronal death.

Cholinergic neuronal degeneration after axotomy has been proposed to be due to the loss of a retrogradely transported neurotrophic factor, possibly nerve growth factor (NGF). To test this hypothesis, NGF was continuously infused into the lateral ventricles of adult rats that had received bilateral lesions of all cholinergic axons projecting from the medial septum to the dorsal hippocampus. After 2 weeks of NGF treatment, identification of cholinergic neurons by the presence of the biosynthetic enzyme choline acetyltransferase revealed a dramatic increase (350%) in the survival of the axotomized septal cholinergic neurons. Thus, NGF or an NGF-like molecule can act as a neurotrophic factor for these neurons.