Region-specific activation of microglial cells in the rat septal complex following fimbria-fornix transection

Studies of postlesional microglial activation may gain insight into microglia/neuronal interactions in processes of neurodegeneration. We compared the microglial response after axotomy of septohippocampal projection neurons with that seen after selective immunolesioning of cholinergic septohippocampal neurons with the immunotoxin 192 IgG-saporin. Using the microglial marker isolectin B4 from Griffonia simplicifolia (GSA I-B4), we found striking differences in the microglial response between these two lesion paradigms. Following axotomy of septohippocampal neurons by fimbria-fornix transection (ff-t), there was only a moderate and short-lasting microglial reaction in the medial septum (MS) in the early postlesion period. Prelabeling of septohippocampal neurons with Fluoro-Gold (FG) prior to axotomy revealed the survival of most neurons, and only very rarely were microglial cells observed that had phagocytosed FG-labeled debris. In the lateral septum (LS) containing the degenerating terminals of hippocamposeptal fibers transected by ff-t, a heavy reaction of lectin-labeled activated microglial cells associated with high phagocytotic activity was noticed. Unexpectedly, after a long survival time (6 months) following ff-t, we observed an increase in microglial GSA I-B4 labeling in the MS. In contrast, an inverse pattern of the microglial response, i.e., a strong initial reaction in the MS and very little microglial activation in the LS, was observed after immunolesioning. Our results indicate that the microglial reaction in the MS following ff-t differs substantially from that seen in other models of axotomy.     

Differential regulation of expression of rat hippocampal muscarinic receptor subtypes following fimbria-fornix lesion

Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspiration lesions of the fimbria-fornix to produce cholinergic denervation of the hippocampus, non-M1 receptors (non-pirenzepine displaceable [3H]quinuclindinyl benzilate binding sites) in the hippocampus were increased significantly, which correlated with increases in the levels of hippocampal m3 and m4 receptor mRNAs (m3: +24% and m4: +41%). These findings indicate that multiple muscarinic receptor subtypes are expressed in the hippocampus with the m3 and m4 subtypes predominantly postsynaptic to the septohippocampal cholinergic terminals.     

Lesions of rat perirhinal cortex exacerbate the memory deficit observed following damage to the fimbria-fornix.

Rats that had received bilateral lesions of the perirhinal cortex, fimbria-fornix, combined lesions of both these structures, or sham operations were tested on an object-guided delayed non-match-to-sample task. Perirhinal lesioned and fimbria-fornix lesioned rats were moderately impaired when delay intervals of 30 s or more were introduced between the sample and test phases of the experiment. Animals with combined lesions displayed a considerably greater impairment than animals with lesions of either structure alone. The combined lesioned animals were severely impaired in the initial acquisition of the task and displayed a profound memory deficit at delay intervals of greater than 4 s. These results emphasize the importance of the perirhinal cortex to memory function and suggest that the perirhinal cortex and the hippocampal formation may function interactively in the execution of memory processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reduction of vesicular acetylcholine transporter mRNA in the rat septum following lead exposure

We have previously observed that maternal exposure to lead (Pb) results in a reduction of levels of mRNA coding for cholineacetyltransferase (ChAT) in the septum of developing rat without affecting the dams. Here we report that Pb similarly affects the expression of vesicular acetylcholine transporter (VAChT) mRNA in the rat septum. In close agreement with the time course of ChAT mRNA expression, septal VAChT mRNA levels increased from 30% at postnatal day 7 to 78% and 100% of adult levels at days 14 and 21, respectively. Maternal exposure to 0.2% lead acetate in drinking water from gestational day 16 resulted in an approximately 30% reduction of VAChT in 7 and 21-day-old rat pups without affecting VAChT mRNA levels in the dams. These results indicate a developmental stage-dependent interference by Pb with ChAT/VAChT gene expression in the rat septum.     

Recovery of structure and function following transection of the primary olfactory nerves in pigeons.

Studied the function of the pigeon's olfactory system before and after bilateral sectioning of the olfactory nerves. 4 adult pigeons were used in each of 3 experiments; 8 normal controls were used in Exp I. All transected nerves were found to be healed 189-302 days after sectioning. Electrical recording from the regenerated nerves revealed apparently normal receptor function and, indirectly, autonomic reflex responsiveness. Previously untrained Ss learned an olfactory discrimination after reconstitution of the peripheral olfactory system using a conditioned suppression procedure. The olfactory nerves of trained Ss were sectioned and the behavioral response recovered within 16-82 days. The gross sizes of primary olfactory nerves and olfactory bulbs were frequently much less than those of controls, but on the ultrastructural level there was no recognizable morphological deficiency in the receptor cellular organelles or terminal synaptic contacts in bulbar glomeruli. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased 5-HT1A receptor immunoreactivity in the rat hippocampus following 5,7-dihydroxytryptamine lesions in the cingulum bundle and fimbria-fornix

Serotonin (5-HT) projections from the ascending raphe nuclei reach the dorsal hippocampus via the cingulum bundle (CB) and fimbria-fornix (FF). Microinjection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the CB and FF produces a significant decrease in the density of 5-HT immunoreactive fibers in the hippocampus as early as 3 days postlesion (Zhou, F.C. and Azmitia, E.C. (1983) Brain Res. Bull., 373, 337-348). In the present study we used an anti-peptide antibody against the second extracellular loop of the 5-HT1A receptor and employed immunocytochemistry to examine changes in the expression and distribution of the 5-HT1A receptor in the hippocampus 14 days following administration of 5,7-DHT into the CB and FF. The density of 5-HT immunoreactive fibers was greatly reduced 14 days following the lesions. 5-HT1A immunoreactivity (IR) was localized to the proximal axon near the axon hillock of cells in the pyramidal cell layer of the cornu Ammonus and in the granule cell layer of the dentate gyrus. The intensity of 5-HT1A-IR was increased in the CA1 and dentate gyrus following 5,7-DHT lesions. Intensity in the CA3 also increased but not to a significant level. These findings demonstrate that 5-HT denervation in the hippocampus is followed by increased expression of the 5-HT1A receptor protein. These changes in receptor expression 14 days postlesion may represent adaptive changes by postsynaptic cells following reduced 5-HT innervation and may be the molecular basis for 5-HT1A receptor supersensitivity.     

Hippocampal grafts of acetylcholine-producing cells are sufficient to improve behavioural performance following a unilateral fimbria-fornix lesion

Lesions of the septohippocampal pathway produce cognitive deficits that are partially attenuated by grafts of cholinergic-rich tissue into denervated target regions or by systemic administration of cholinomimetic drugs. In the present study, fibroblasts engineered to produce acetylcholine were used to test the hypothesis that restoration of hippocampal acetylcholine in rats with septohippocampal lesions is sufficient to improve cognitive processing post-damage. Rats received unilateral grafts of acetylcholine-producing or control fibroblasts into the hippocampus immediately prior to an aspirative lesion of the ipsilateral fimbria-fornix. Some rats with fimbria-fornix lesions were implanted with acetylcholine-producing or control fibroblasts into the neocortex, another major target of the basal forebrain cholinergic system, to determine if the site of acetylcholine delivery to the damaged brain is critical for functional recovery. Rats were tested in a hidden platform water maze task, a cued water maze task and activity chambers between one and three weeks post-grafting. Compared to unoperated controls, rats with fimbria fornix lesions only were significantly impaired in hidden platform water maze performance. Hippocampal grafts of acetylcholine-producing cells reduced lesion-induced deficits in the water maze, whereas hippocampal control grafts and cortical grafts of either cell type were without effect. Locomotor activity and cued water maze performance were unaffected by the lesion or the implants. Taken together, these data indicate that water maze deficits produced by fimbria fornix lesions, which disrupt a number of hippocampal neurotransmitter systems, can be attenuated by target specific replacement of acetylcholine in the hippocampus and that this recovery occurs in the absence of circuitry repair.     

Forgetting in rats following medial septum or mammillary body damage.

Examined the effects of medial septal (MS) and mammillary body (MB) radio-frequency lesions in an automated delayed-matching-to-sample (DMTS) procedure using lever-position stimuli and rats. Memory performance pre- and postsurgery was assessed with a negative exponential decay function fitted to bias-free measures of recognition. Part 1 showed that MS, but not MB or sham-control surgery, impaired DMTS performance. This impairment in the MS group was best characterized as an increase in the rate of forgetting. Part 2 examined the interaction between MS and MB lesion effects and proactive interference arising from responses made on the previous DMTS trial. The results indicated that proactive interference effects were similar for all groups. These results provide further support for the critical role of the MS region in memory function but indicate that damage to this brain region does not disrupt memory function through a heightened sensitivity to proactive interference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of mossy fiber sprouting following bilateral transection of the fimbria/fornix

Lesions of the fimbria/fornix (FF) lead to a variety of epileptiform changes in hippocampal activity. In epilepsy, as well as in several experimental preparations of epilepsy, aberrant sprouting of the dentate gyrus mossy fibers (MF) is observed and has been hypothesized to play a critical role in the generation of seizure activity. We therefore sought to determine whether MF sprouting also follows FF transections. FF transections did indeed lead to MF sprouting, which became apparent at 14 days and reached asymptotic levels at 28 days post-lesion. These results indicate a possible mechanism for the epileptiform activity seen following FF lesions and provide an additional example of the diverse epileptogenic treatments that are accompanied by MF sprouting.     

Ultrastructural analysis of periapical granulomas

A large portion of periapical granulomas is composed by cells of the mononuclear-phagocyte and lymphoid system. The ultrastructural features of the monocytes/macrophages differ in relationship to the state of activity of the cells (phagocytosis or secretion). A close correlation between cells of these two systems can be surmised by their tight contacts. An important role in the bone resorption is probably played by cytokines like IL-1 and TNF.     

Enhanced frustrative nonreward effect following 6-hydroxydopamine lesions of the lateral septum in the rat.

Tested the effect of local injections of 6-hydroxydopamine (6-OHDA [3 μg/1 μl]) into the lateral septum in a paradigm that leads to an energizing behavior, through a possible frustrative effect, induced by partial or total omission of reward in hungry adult male Sprague-Dawley rats. Biochemical assays in the septum showed that 6-OHDA reduced endogenous dopamine and, to a lesser extent, noradrenaline concentrations and left intact noncatecholaminergic neurons such as serotoninergic terminals. In a double straight alley, Ss were exposed to an acquisition phase, a partially reinforced phase, and an extinction phase. Ss with lesions ran faster for food than controls in the partial reinforcement or extinction situation. The 2 groups also behaved similarly after the 1st 6 trials of the extinction phase. When Ss were tested in a leverpress conditioning task, lesioned and control Ss learned this task equally well, both with respect to the number of leverpresses and the time to obtain a fixed number of food pellets. In the 1st 5 min following the omission of reward, the number of leverpresses increased more for the lesioned Ss than for controls, a difference that disappeared in the later stages of the test. Results indicate that the loss of septal dopaminergic innervation produces behavioral effects similar to those obtained after total destruction of the same areas by electrocoagulation. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Axonal accumulation of p75NTR and TrkA in the septum following lesion of septo-hippocampal pathways

Septal cholinergic neurones depend on trophic support by nerve growth factor (NGF) which can rescue them from injury-induced degeneration. Since NGF exerts its effects via p75NTR and TrkA receptors coexpressed in vast majority of these neurones and down-regulated without NGF treatment after injury, in this study we aimed to examine how does the lesion to the cholinergic tracts affect distribution of both types of receptor proteins in damaged fibres. Early changes (two and seven days) were examined immunocytochemically within the septum and supracallosal stria after unilateral lesion to the supracallosal area and cingulum transecting some septal cholinergic efferents. We found accumulation of p75NTR and TrkA immunoreactive material (so-called "pile-up") within axonal segments of distended appearance proximal to the transection at two days postlesion and its translocation towards cell bodies seven days postsurgery. We observed p75NTR pile-up to be more intense than TrkA, which may indicate different cellular concentrations of both receptors. Receptor pile-up resembled acetylcholinesterase pile-up reported previously, suggesting a common response mechanism involving axonal transport disturbances.     

Ultrastructural changes in the supraoptic nucleus and posterior lobe of the pituitary following experimental burns

The dynamics of the ultrastructure of the neurosecretory system in the postburn period is characterized by phasic of organells of neurosecretory cells and synapses on their bodies and processes. Immediately after burn there appear pronounced signs of an increased formation of secretion synchronous to a considerably increased functional activity of synaptic structures. Of the opposite character are fine structures in neurocytes in the subsequent period (1-1,5 hour after burn). Phenomena of disintegration and degeneration of organells are developing in the cells. In the posiologically active neurohormones and degeneration of membrane structures gradually increase at all the observed stages of the burn trauma. All the elements of the supraoptic nucleus and the posterior lobe of the hypophysis early responding to the effect of such a powerful extreme factor are involved in the response of the organism to burn. It should be noted that immediately after burn there appears an increased permeability of capillaries followed by extravasation of formed elements and liquid blood. It steadily increases with the development of the process.     

Ultrastructural evaluation following catheterization of the fallopian tube with a hysteroscopic catheter

PURPOSE: The purpose of this study was to determine the in vitro effects of a resin-modified glass-ionomer restorative material on human enamel. METHODS: Enamel specimens were restored with Photac-Fil, a resin-modified glass ionomer; Ketac-Fil, an autopolymerizing glass ionomer and silver amalgam. The samples were pH cycled and then subjected to an artificial caries challenge. Specimens were evaluated by fluoride microdrill biopsy and quantitative microradiography at 1, 2, and 3 mm from restorations. Data on fluoride content, lesion depth, and mineral content were analyzed by one-way ANOVA, Student's t test, Neuman-Keuls procedure (multiple [pairwise] comparison), and Pearson's product-moment correlation tests. RESULTS: There were significant differences in fluoride uptake, lesion depth, and mineral density between groups. Significant correlational relationships were also determined. CONCLUSION: This study demonstrates that Photac-Fil and Ketac-Fil prevent in-vitro demineralization of enamel and suggests different mechanisms of action for each material.     

Autotomy in rats following peripheral nerve transection is attenuated by preceding formalin injections into the same limb

The influence of an evolving painful inflammatory lesion on the development of autotomy, a behavioural model of denervation pain, was studied in rats suffering sciatic and saphenous nerves transection 30 or 60 min, and 1, 3, 7 or 14 days after being injected with formalin (50 microl, 5%, s.c). Hindpaws pressure and heat nociceptive thresholds and volume of the injected paw were assessed, in non-operated rats, at the above time-points. The main effects on autotomy were: (1) a significant attenuation when formalin injection preceded the neurectomies by 1 day or more, a period characterized by hypalgesia of the injected paw to both mechanical (during the first week) and thermal (spanning up to the third day after formalin) stimuli and inflammation (lasting for 14 days); (2) a significantly earlier onset when formalin was injected 30 min before neurectomies. Possible mechanisms linking nociceptive responsiveness and inflammation to the development of autotomy are discussed.     

Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection

We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.     

Anterior resection following posterior transsacral stapling and transection of the anal canal for low-lying rectal cancer in males

In anterior resection with anastomosis using the double-staple technique for low-lying rectal cancer in male patients, the approach to the anal canal with a stapling instrument via the abdominal area is limited by the narrow pelvis. The stapling and transection of the anal canal via the posterior transsacral approach prior to performing an anterior resection thus enables the lower rectum and anal canal to be visualized, so that the anal canal can be accurately stapled and transected even in male patients with a narrow pelvis.     

Complement activation and CD59 expression in the motor facial nucleus following intracranial transection of the facial nerve in the adult rat

Intracranial transection of the facial nerve has been shown to cause a massive neuronal cell death in the motor facial nucleus. Complement activation has been proposed to contribute to neuronal degeneration following axotomy. Using immunocytochemistry and in situ hybridization we show in the present study that there is complement activation in the facial nucleus after intracranial facial nerve transection as well as increase of the complement regulators CD59 and clusterin. We propose a neuroprotective role for the complement regulators CD59 and clusterin against homologous attack of complement to facial motor neurons.