Efficacy of Transurethral Vesical Deafferentation with Mid-Urethral Sling Operation for Female Mixed Urinary Incontinence: Preliminary Results.

OBJECTIVES: In female patients with mixed urinary incontinence (MUI), a mid-urethral sling operation (MUS) is an effective treatment for stress urinary incontinence (SUI), but urgency urinary incontinence (UUI) frequently persists. We developed a novel transurethral vesical deafferentation procedure and assessed its efficacy in these patients. METHODS: From December 2009 to December 2012, 41 female patients with MUI were enrolled prospectively. After baseline evaluation including urodynamic study and symptom questionnaires (Overactive Bladder Symptom Score (OABSS) and International Consultation on Incontinence Questionnaire - Overactive Bladder [ICIQ-OAB]), patients in the study group underwent both the deafferentation procedure and MUS, and those in the control group underwent MUS alone. The outcome was assessed 3 months after the operation by subjective assessment of SUI and OABSS. RESULTS: At 3 months, the treatment response rate of UUI was significantly higher in the study group than in the control group; UUI was improved in 80 and 57.1% of patients, respectively. SUI was cured in most patients. There were no serious complications, such as voiding symptom and urinary retention. CONCLUSIONS: The transurethral vesical deafferentation procedure combined with MUS is effective for the treatment of MUI. The procedure is simple, safe and efficacious in treating urgency and UUI without affecting voiding function.

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension.

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼ 140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼ 170 mmHg. RDNX reduced MAP ∼ 10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves.

Cardiac sympathetic afferent denervation attenuates cardiac remodeling and improves cardiovascular dysfunction in rats with heart failure.

The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympathoexcitation in chronic heart failure (CHF). Increased sympathoexcitation is positively related to mortality in patients with CHF. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here, we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. To delete the transient receptor potential vanilloid 1 receptor-expressing CSAR afferents selectively, epicardial application of resiniferatoxin (50 µg/mL), an ultrapotent analog of capsaicin, was performed during myocardium infarction surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of resiniferatoxin largely prevented the elevated left ventricle end-diastolic pressure, lung edema, and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart, and increased cardiac contractile reserve in response to ß-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that resiniferatoxin attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and transforming growth factor-ß receptor I in CHF rats. Pressure-volume loop analysis showed that resiniferatoxin reduced the end-diastolic pressure volume relationships in CHF rats, indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF.

Consequences of the ablation of nonpeptidergic afferents in an animal model of trigeminal neuropathic pain.

Damage to peripheral nerves causes significant remodeling of peripheral innervation and can lead to neuropathic pain. Most nociceptive primary afferents are unmyelinated (C fibers) and subdivided into peptidergic and nonpeptidergic fibers. Previous studies have found nerve injury in the trigeminal system to induce changes in small-diameter primary afferent innervation and cause significant autonomic sprouting into the upper dermis of the lower-lip skin of the rat. In this study, we used the ribosomal toxin, saporin, conjugated to the lectin IB4 to specifically ablate the nonpeptidergic nociceptive C fibers, to see if loss of these fibers was enough to induce autonomic fiber sprouting. IB4-saporin treatment led to specific and permanent ablation of the IB4-positive, P2X(3)-immunoreactive fibers and led to sprouting of parasympathetic fibers into the upper dermis, but not of sympathetic fibers. These changes were associated with significant increase in glial-derived nerve growth factor levels in the lower-lip skin. While IB4-saporin treatment had no effect on evoked mechanical thresholds when von Frey hairs were applied to the lower-lip skin, ablation of nonpeptidergic fibers in a chronic constriction injury model caused significant sympathetic and parasympathetic fiber sprouting, and led to an exacerbated pain response. This was an unexpected finding, as it has been suggested that nonpeptidergic fibers play a major role in mechanical pain, and suggests that these fibers play a complex role in the development of neuropathic pain.

Return of spinal reflex after spinal cord surgery for brachial plexus avulsion injury.

Motor but not sensory function has been described after spinal cord surgery in patients with brachial plexus avulsion injury. In the featured case, motor-related nerve roots as well as sensory spinal nerves distal to the dorsal root ganglion were reconnected to neurons in the ventral and dorsal horns of the spinal cord by implanting nerve grafts. Peripheral and sensory functions were assessed 10 years after an accident and subsequent spinal cord surgery. The biceps stretch reflex could be elicited, and electrophysiological testing demonstrated a Hoffman reflex, or Hreflex, in the biceps muscle when the musculocutaneous nerve was stimulated. Functional MR imaging demonstrated sensory motor cortex activities on active as well as passive elbow flexion. Quantitative sensory testing and contact heat evoked potential stimulation did not detect any cutaneous sensory function, however. To the best of the authors' knowledge, this case represents the first time that spinal cord surgery could restore not only motor function but also proprioception completing a spinal reflex arch.

Relative contributions of afferent vagal fibers to resistance to diet-induced obesity.

BACKGROUND: We previously demonstrated vagal neural pathways, specifically subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium-glucose cotransporter SGLT1, the intestinal transporter responsible for absorption of dietary glucose. We hypothesized targeting this pathway could be a novel therapy for obesity. We therefore tested the impact of disrupting vagal signaling by total vagotomy or selective vagal de-afferentation on weight gain and fat content in diet-induced obese rats. METHODS: Male Sprague-Dawley rats (n = 5-8) underwent truncal vagotomy, selective vagal de-afferentation with capsaicin, or sham procedure. Animals were maintained for 11 months on a high-caloric Western diet. Abdominal visceral fat content was assessed by magnetic resonance imaging together with weight of fat pads at harvest. Glucose homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene expression was assessed by qPCR and immunoblotting and function by glucose uptake in everted jejunal sleeves. RESULTS: At 11-months, vagotomized rats weighed 19% less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams. Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P = 0.039) in visceral abdominal fat, respectively. There were no changes in blood glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged across all cohorts at 11-months postoperatively. CONCLUSIONS: Truncal vagotomy led to significant reductions in both diet-induced weight gain and visceral abdominal fat deposition. Vagal de-afferentation led to a more modest, but clinically and statistically significant, reduction in visceral abdominal fat. As increased visceral abdominal fat is associated with excess morbidity and mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery.

[Effect of inferior vestibular and part of mandibular branch of trigeminal neurotomy on sound-induced masseter reflex potentials].

OBJECTIVE: To evaluate the influence of inferior vestibular and part of mandibular branch of trigeminal neurotomy on sound-induced masseter reflex potentials. METHOD: Twenty guinea pigs were randomly divided into four groups, including 5 normal control guinea pigs, 5 received unilateral inferior vestibular neurotomy, 5 received unilateral inferior alveolar nerve neurotomy, and 5 received auriculotemporal nerve neurotomy. Click sound-induced masseter reflex potentials were recorded in four groups, respectively. RESULT: The thresholds of negative peak (NP) of click sound-induced masseter reflex potentials in normal control group were (90.00 +/- 8.16) dBnHL. The response rates of the NP of the masseter reflex potentials using 100, 90, 80 and 70 dBnHL monaural acoustic stimulation with unilateral recording were 100%, 70%, 40% and 0, respectively. The mean latencies of the NP were (6.55 +/- 0.25) ms, (6.61 +/- 0.16) ms and (6.70 +/- 0.13) ms, when elicited by 100,90 and 80 dBnHL acoustic stimulation respectively. There was no significant difference between the stimulus intensity and the mean latency of the NP (P > 0.05). Negative peak of click sound-induced masseter reflex potentials was not observed in the inferior vestibular neurotomy group. The NP was preserved in the inferior alveolar nerve and auriculotemporal nerve neurotomy groups. There were no significant difference of the mean thresholds and latencies of NP between normal control group and inferior alveolar nerve and auriculotemporal nerve neurotomy group (P > 0.05). CONCLUSION: Click sound-induced masseter reflex potentials originates from vestibular afferents. Afferent of inferior alveolar nerve and auriculotemporal nerve can not influence the vestibular evoked masseter reflex potentials.

Histological modifications of the rat prostate following transection of somatic and autonomic nerves

It is known that hormones influence significantly the prostate tissue. However, we reported that mating induces an increase in androgen receptors, revealing a neural influence on the gland. These data suggested that somatic afferents (scrotal and genitofemoral nerves) and autonomic efferents (pelvic and hypogastric nerves) could regulate the structure of the prostate. Here we assessed the role of these nerves in maintaining the histology of the gland. Hence, afferent or efferent nerves of male rats were transected. Then, the ventral and dorsolateral regions of the prostate were processed for histology. Results showed that afferent transection affects prostate histology. The alveoli area decreased and increased in the ventral and dorsolateral prostate, respectively. The epithelial cell height increased in both regions. Efferent denervation produced dramatic changes in the prostate gland. The tissue lost its configuration, and the epithelium became scattered and almost vanished. Thus, afferent nerves are responsible for spinal processes pertaining to the trophic control of the prostate, activating its autonomic innervation. Hence, our data imply that innervation seems to be synergic with hormones for the healthy maintenance of the prostate. Thus, it is suggested that some prostate pathologies could be due to the failure of the autonomic neural pathways regulating the gland.

Sabe-se que os hormônios influenciam significativamente o tecido prostático. Entretanto, nós demonstramos que o acasalamento induz um aumento nos receptores androgênicos, revelando uma influência neural sobre a glândula. Esses dados sugerem que os aferentes somáticos (nervos escrotal e genito-femural) e os eferentes autonômicos (nervos pélvicos e hipo-gástricos) poderiam regular a estrutura da próstata. Neste trabalho, avaliou-se a função destes nervos na manutenção da histologia da glândula. Dessa forma, os nervos aferentes e eferentes de ratos machos foram seccionados As regiões ventral e dorsolateral da próstata foram processadas para histologia. Os resultados mostraram que a transecção aferente afeta a histologia da próstata. A área alveolar diminuiu e aumentou na próstata dorsal e dorsolateral, respectivamente. A altura da célula epitelial aumentou em ambas as regiões. A desenervação eferente produziu alterações dramáticas na glândula prostática. O tecido perdeu a sua configuração e o epitélio tornou-se difuso e quase desapareceu. Assim, os nervos aferentes são responsáveis por processos espinhais que pertencem ao controle trófico da próstata, ativando sua inervação autonômica. Dessa forma, nossos dados sugerem que a inervação parece ser sinérgica com os hormônios para a manutenção saudável da próstata. Assim, sugere-se que algumas patologias prostáticas poderiam ser ocasionadas devido a falhas nas vias neurais autonômicas que regulam esta glândula.

Gamma Knife irradiation-induced histopathological changes in the trigeminal nerves of rhesus monkeys.

OBJECT: The authors' goal was to observe histopathological changes in the trigeminal nerve after Gamma Knife surgery (GKS) in rhesus monkeys, and to investigate the radiobiological mechanism of GKS for primary trigeminal neuralgia. The nerve length-dosage effect of irradiation is also discussed. METHODS: One of 5 rhesus monkeys randomly served as a control, and the other 4 monkeys were randomly administered a target radiation dose of 60, 70, 80, or 100 Gy (a different dose in each animal). The size of the collimator was 4 mm, and the target point was the trigeminal nerve root. In each experimental monkey, one side was exposed to single-target-point irradiation, and the contralateral side was exposed to double-target-point irradiation. After 6 months, the trigeminal nerve root was examined using light microscopy, transmission electron microscopy, and immunohistochemistry. RESULTS: At each radiation dose, the damage to the nerve tissue by single-target-point irradiation was identical to that caused by double-target-point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy, there was limited nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nerve tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there was severe derangement in the structure of the nerve tissue, and extensive demyelination, fragmentation, and loss of axons. CONCLUSIONS: The target doses of 60 and 70 Gy have very little impact on the structure of the trigeminal nerve. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100-Gy dose can cause some necrosis of neurons. Comparing the single-target-point with the double-target-point irradiation, the extent of damage to the nerve tissue is identical, and no difference in the nerve length-dosage effect was found.

[Presurgical functional magnetic resonance imaging]. / Prächirurgische funktionelle Magnetresonanztomographie.

Functional magnetic resonance imaging (fMRI) is an important and novel neuroimaging modality for patients with brain tumors. By non-invasive measurement, localization and lateralization of brain activiation, most importantly of motor and speech function, fMRI facilitates the selection of the most appropriate and sparing treatment and function-preserving surgery. Prerequisites for the diagnostic use of fMRI are the application of dedicated clinical imaging protocols and standardization of the respective imaging procedures. The combination with diffusion tensor imaging (DTI) also enables tracking and visualization of important fiber bundles such as the pyramidal tract and the arcuate fascicle. These multimodal MR data can be implemented in computer systems for functional neuronavigation or radiation treatment. The practicability, accuracy and reliability of presurgical fMRI have been validated by large numbers of published data. However, fMRI cannot be considered as a fully established modality of diagnostic neuroimaging due to the lack of guidelines of the responsible medical associations as well as the lack of medical certification of important hardware and software components. This article reviews the current research in the field and provides practical information relevant for presurgical fMRI.

Pre-treatment with lidocaine suppresses ectopic discharges and attenuates neuropeptide Y and c-Fos expressions in the rat cuneate nucleus following median nerve transection.

Following peripheral nerve injury, lidocaine application has been demonstrated to suppress injury discharges. However, there is very little information about the effects of lidocaine pre-treatment. The aim of the present study was to examine the effects of pre-treatment with lidocaine on injury discharges of the nerve, and neuropeptide Y (NPY) and c-Fos expression in the cuneate nucleus (CN) after median nerve transection (MNT). Rats received either saline or 1%, 5%, or 10% lidocaine applied topically to the median nerve before nerve transection. Electrophysiological recording was used to examine the changes in injury discharges of the nerve at post-injection, transection, pre- and post-electrical stimulation stages in the different groups. Sequential immunohistochemistry was also used to identify the number of NPY-like immunoreactive (NPY-LI) fibers and c-Fos-LI cells in the corresponding CN. An increasing frequency of injury discharges was observed at all stages in the pre-saline group, which were suppressed by lidocaine pre-treatment in a dose-dependent manner. Lidocaine pre-treatment also attenuated the number of injury-induced NPY-LI fibers and c-Fos-LI neurons within the CN in a dose-dependent manner. Furthermore, expression of c-Fos-LI neurons in the CN was significantly reduced by an NPY receptor antagonist, indicating that NPY modulated c-Fos expression following MNT. These data suggest that preventing injury discharges with lidocaine pre-treatment can effectively attenuate central sensitization following MNT.

Assessment of the corona radiata sensory tract using awake surgery and tractography.

Anatomical localization of brain function can be achieved by functional changes during awake surgery combined with tractography constructed by diffusion tensor imaging studies. We aimed to use these techniques to characterize the sensory tract in the corona radiata in patients with closely associated brain tumors. Of nine patients who had brain tumors in the primary sensory area (S1) and who underwent awake surgery between October 2004 and July 2007, two patients showed deterioration in deep sensation during and after awake surgery. Both of these patients also developed involuntary movements (for patient 1 this was myoclonus of the left hand, while patient 2 experienced unintentional lifting of the arm). In these two patients, tumors were located just beside the sensory tract in the corona radiata of the right hemisphere. In patient 2, Wallerian degeneration of the sensory tract and concomitant deterioration of superficial and deep sensation were observed at 6 months after awake surgery. These results suggest that damage to a closely associated sensory tract in the corona radiata is critical to the development of sensory deficits and involuntary movements. For patients who undergo surgical resection of S1 brain tumors, pre-operative tractography to detect the sensory tract in the corona radiata may allow protection of the sensory tract during awake surgery, thereby preventing post-operative sensory deficits.

Bypassing spinal cord injury: surgical reconstruction of afferent and efferent pathways to the urinary bladder after conus medullaris injury in a rat model.

Afferent and efferent nerve function in the atonic bladder caused by conus medullaris injury in a rat model was established by intradural microanastomosis of the left L5 ventral root (VR) to right S2 VR to restore pure motor-to-motor reinnervation coupled with extradural postganglionic spinal nerve transfer of L5 dorsal root (DR) to S2 DR for pure sensory-to-sensory reinnervation. Early function of the reflex arc was evaluated by electrophysiological study, as well as by intravesicular pressure measurement and histological examination. The results demonstrated that single focal stimulation of the left S2 DR elicited evoked potentials at the left vesicular plexus before and after horizontal spinal cord damage between the L6 and S4 level. Bladder contraction was successfully initiated by trains of stimuli targeting the left L5-S2 DR anastomosis. Achievable bladder pressures and amplitude of bladder smooth muscle complex action potentials were unchanged before and after induced paraplegia and comparable to those of the control. Prominent axonal sprouting was seen in the distal part of nerve graft. Both afferent and efferent nerve pathways in the atonic bladder can be reconstructed by suprasacral motor-to-motor and sensory-to-sensory nerve transfer after spinal cord injury in rats. This reconstructive strategy has significant potential in clinical application.

Reconstruction of reflex pathways to the atonic bladder after conus medullaris injury: preliminary clinical results.

Neurogenic bladder dysfunction following spinal cord injury is a major medical and social problem for which there is no ideal treatment strategy. In this study, spinal root anastomoses were performed in 10 paraplegic patients with traumatic lesions of the conus medullaris, in an attempt to reinnervate the paralyzed bladder. For the operation, the functional T11 ventral root (VR) above the lesion was transected and anastomosed to the S2 ventral roots unilaterally through a nerve graft. The T11 dorsal root was left intact as the trigger for micturition after axonal regeneration. All patients underwent urodynamic evaluation before surgery and at follow-up. The mean follow-up duration was 2 years. Of the 10 patients, 7 (70%) regained satisfactory bladder control within 18-24 months after VR microanastomosis. In these seven patients, the average bladder capacity decreased from 508 +/- 83 (mean +/- SD) to 370 +/- 59 ml, residual urine decreased from 477 +/- 98 to 35 +/- 11 ml, and urinary infections were not observed. Patients with impaired renal function experienced a full recovery. Three patients failed to show any improvement after the operation. These results suggest that a restitutive process occurs in the bladder following reinnervation from new T11 VR connections to the bladder nerves. Spinal cord lesions that may benefit from such a nerve crossover surgery are those located at the conus, whereby a functional suprasacral nerve can be connected to the sacral roots to bypass the injury in an attempt to restore central connections to the bladder.

Percutaneous computed tomography-guided radiofrequency ablation of upper spinal cord pain pathways for cancer-related pain.

OBJECTIVE: The author presents data to support the continued need for ablative procedures, particularly cordotomy, in the management of cancer-related pain. METHODS: Fifty-one patients with cancer-related body or face pain were treated with computed tomography-guided radiofrequency ablation of the spinothalamic tract or trigeminal tract nucleus in the upper cervical region of the spinal cord. Forty-one patients underwent a unilateral cervical cordotomy, and 10 patients underwent a trigeminal tractotomy-nucleotomy. Three methods to assess patient pain were used: degree of pain relief, Visual Analog Scale, and total sleeping hours. The Karnofsky scale was used to measure the patient's level of function pre- and postprocedure. RESULTS: After surgical intervention, patients reported initial and 6-months follow-up pain relief as 98 and 80%, respectively. CONCLUSION: Computed tomography-guided ablation of the upper cervical spinal cord is a safe and effective procedure to treat cancer pain involving the body or face. There remains a need for ablative procedures, in particular cordotomy, in the management of cancer-related pain.

Subjective visual tilt and lateral instability after vestibular deafferentation.

CONCLUSION: Defective utricular function, reflected by deviation of the perceived visual horizontal or vertical, cannot by itself explain increased postural sway in the lateral direction for patients with unilateral vestibular deafferentation (uVD). OBJECTIVE: It is not known why some patients with chronic uVD report distressing unsteadiness while others do not. The objective of this study was to test the hypothesis that impaired utricular compensation, reflected by pathologic tilt in the subjective visual horizontal and vertical (SVH-V) test, would affect postural control in the lateral direction after uVD. PATIENTS AND METHODS: The SVH-V was tested in 28 patients 6 months after translabyrinthine surgery for unilateral vestibular schwannoma, and correlated with posturography results. RESULTS: No increase in lateral and anterior-posterior sway, or the quotients between them, or for Romberg quotients, was found with increasing SVH-V tilt.

Spinal cord stimulation is an effective treatment for the chronic intractable visceral pelvic pain.

OBJECTIVE: Recent studies have demonstrated significant involvement of dorsal column pathways in transmission of visceral pelvic pain. Spinal cord stimulation (SCS) suppresses visceral response to colon distension in an animal model and therefore may be an effective therapy for chronic pelvic pain of visceral origin. We are reporting on the value of neurostimulation for chronic visceral pelvic pain in six female patients with the diagnosis of long-standing pelvic pain (history of endometriosis, multiple surgical explorations, and dyspareunia). DESIGN AND SETTINGS: Case-series report. All patients received repeated hypogastric blocks (in an average of 5.3 blocks) with a significant pain relief for a period ranging from 1 to 6 weeks. Three received neurolytic hypogastric block with the pain relief of 3, 8, and 12 months, respectively. Following psychological evaluation and clearance by our Multidisciplinary Committee on Implantable Devices, they all underwent SCS trial for 7-14 days. All patients received SCS systems with dual leads (Compact or Quad leads, Medtronic Inc., Minneapolis, MN, USA). RESULTS: The average follow-up was 30.6 months. Median visual analog scale pain score decreased from 8 to 3. All patients had more than 50% of the pain relief. Pain Disability Index changed from an average of 57.7 +/- 12 to 19.5 +/- 7. Opiate use decreased from an average 22.5 mg to 6.6 mg of morphine sulfate milligram equivalents per day. CONCLUSION: It appears that SCS may have a significant therapeutic potential for treatment of visceral pelvic pain.

Subcortical deafferentation impairs behavioral reinforcement of long-term potentiation in the dentate gyrus of freely moving rats.

Long-term potentiation is a form of neural functional plasticity which has been related with memory formation and recovery of function after brain injury. Previous studies have shown that a transient early-long-term potentiation can be prolonged by direct stimulation of distinct brain areas, or behavioral stimuli with a high motivational content. The basolateral amygdala and other subcortical structures, like the medial septum and the locus coeruleus, are involved in mediating the reinforcing effect. We have previously shown that the lesion of the fimbria-fornix--the main entrance of subcortical afferents to the hippocampus--abolishes the reinforcing basolateral amygdala-effects on long-term potentiation in the dentate gyrus in vivo. It remains to be investigated, however, if such subcortical afferents may also be important for behavioral reinforcement of long-term potentiation. Young-adult (8 weeks) Sprague-Dawley male rats were fimbria-fornix-transected under anesthesia, and electrodes were implanted at the dentate gyrus and the perforant path. One week after surgery the freely moving animals were studied. Fimbria-fornix-lesion reduced the ability of the animals to develop long-term potentiation when a short pulse duration was used for tetanization (0.1 ms per half-wave of a biphasic stimulus), whereas increasing the pulse duration to 0.2 ms per half-wave during tetanization resulted in a transient early-long-term potentiation lasting about 4 h in the lesioned animals, comparable to that obtained in non-lesioned or sham-operated control rats. In water-deprived (24 h) control animals, i.e. in non-lesioned and sham-operated rats, early-long-term potentiation could be behaviorally reinforced by drinking 15 min after tetanization. However, in fimbria-fornix-lesioned animals long-term potentiation-reinforcement by drinking was not detected. This result indicates that the effect of behavioral-motivational stimuli to reinforce long-term potentiation is mediated by subcortical, heterosynaptic afferents.

Lithium increases bcl-2 expression in chick cochlear nucleus and protects against deafferentation-induced cell death.

Approximately 20-30% of neurons in the avian cochlear nucleus (nucleus magnocellularis) die following deafferentation (i.e. deafness produced by cochlea removal) and the remaining neurons show a decrease in soma size. Cell death is generally accepted to be a highly regulated process involving various pro-survival and pro-death molecules. One treatment that has been shown to modify the expression of these molecules is chronic administration of lithium. The present experiments examined whether lithium treatment can protect neurons from deafferentation-induced cell death. Post-hatch chicks were treated with LiCl or saline for 17 consecutive days, beginning on the day of hatching. On the 17th day, a unilateral cochlea ablation was performed. Five days following surgery, the nucleus magnocellularis neurons were counted stereologically on opposite sides of the same brains. Lithium reduced deafferentation-induced cell death by more than 50% (9.8% cell death as compared with 22.4% in saline-treated subjects). Lithium did not affect cell number on the intact side of the brain. Lithium also did not prevent the deafferentation-induced decrease in soma size, suggesting a dissociation between the mechanisms involved in the afferent control of soma size and those involved in the afferent control of cell viability. A possible mechanism for lithium's neuroprotective influence was examined in a second set of subjects. Previous studies suggest that the pro-survival molecule, bcl-2, may play a role in regulating cell death following deafferentation. Tissues from lithium- and saline-treated subjects were examined using immunocytochemistry. Chronic administration of lithium dramatically increased the expression of bcl-2 protein in nucleus magnocellularis neurons. These data suggest that lithium may impart its neuroprotective effect by altering the expression of molecules that regulate cell death.

Successful treatment of deep dyspareunia and primary dysmenorrhea with laparoscopic uterosacral nerve ablation (LUNA) procedure.

Deep dyspareunia, often described as pain resulting from pelvic thrusting during sexual intercourse, is relatively common and has many causes. To date, feasible surgical interventions for deep dyspareunia are very rare. The two procedures which have been mentioned in the literature for the treatment of deep dyspareunia were laparoscopic uterosacral ligament ablation (LUNA) and uterine ventrosuspension. We report the case of a young female patient, aged 32, gravida 3, parity 2, presenting with deep dyspareunia and primary dysmenorrhea for 4 years. She had both subjective and objective improvements for dyspareunia and primary dysmenorrhea following LUNA operation. Further large-scaled randomized controlled trial is mandatory to verify the surgical effect of LUNA operation for patients with deep dyspareunia.