Bilateral Transection Research Articles

MP12-14 INVESTIGATIONS INTO THE MECHANISTIC LINK BETWEEN ELEVATED URINE BDNF LEVELS AND EXPRESSION OF CONNEXIN 43 IN BLADDER BIOPSY OF OVERACTIVE BLADDER PATIENTS

behavior was tested at day 14 post-surgery. In order to get sexual receptivity, 48 h previous to the test the females were treated with 10 ,g of benzoate estradiol and 44 h later 2 mg of progesterone was injected. During the coitus the urinary meatus of the female was zoom recorded in order to determine urine expulsion. Means among groups were compared with ANOVA, with P<0.05 indicating a significant difference. RESULTS: Sham surgery did not significantly modified the values of the urinary parameters. However, in DNCNX females voiding frequency (p<0.05) and voiding duration significantly increased (p<0.05). Flow rate, voiding volume and voiding interval were not significantly affected. Seventy percent of the DNCNX animals expelled urine just after a penile intromission or male ejaculation. CONCLUSIONS: These results suggest that genital deaferentation may be a causal factor of female coital urinary incontinence. Rats with bilateral transection of the DNC may be used as an animal model of coital incontinence.

Anxiolytic efficacy of repeated oral capsaicin in rats with partial aberration of oral sensory relay to brain

ObjectiveThis study was conducted to examine if taste over load with oral capsaicin improves the adverse behavioural effects induced by partial aberration of oral sensory relays to brain with bilateral transections of the lingual and chorda tympani nerves. DesignMale Sprague-Dawley rats received daily 1ml of 0.02% capsaicin or water drop by drop into the oral cavity following the bilateral transections of the lingual and chorda tympani nerves. Rats were subjected to ambulatory activity, elevated plus maze and forced swim tests after 11th, 14th and 17th daily administration of capsaicin or water, respectively. The basal and stress-induced plasma corticosterone levels were examined after the end of behavioural tests. ResultsAmbulatory counts, distance travelled, centre zone activities and rearing were increased, and rostral grooming decreased, during the activity test in capsaicin treated rats. Behavioural scores of capsaicin rats during elevated plus maze test did not differ from control rats. Immobility during the swim test was decreased in capsaicin rats with near significance (P=0.0547). Repeated oral capsaicin increased both the basal level and stress-induced elevation of plasma corticosterone in rats with bilateral transections of the lingual and chorda tympani nerves. DiscussionIt is concluded that repeated oral administration of capsaicin reduces anxiety-like behaviours in rats that received bilateral transections of the lingual and chorda tympani nerves, and that the increased corticosterone response, possibly modulating the hippocampal neural plasticity, may be implicated in the anxiolytic efficacy of oral capsaicin.

GAL-021 and GAL-160 are Efficacious in Rat Models of Obstructive and Central Sleep Apnea and Inhibit BKCa in Isolated Rat Carotid Body Glomus Cells.

GAL-021 and GAL-160 are alkylamino triazine analogues, which stimulate ventilation in rodents, non-human primates and (for GAL-021) in humans. To probe the site and mechanism of action of GAL-021 and GAL-160 we utilized spirometry in urethane anesthetized rats subjected to acute bilateral carotid sinus nerve transection (CSNTX) or sham surgery. In addition, using patch clamp electrophysiology we evaluated ionic currents in carotid body glomus cells isolated from neonatal rats. Acute CSNTX markedly attenuated and in some instances abolished the ventilatory stimulant effects of GAL-021 and GAL-160 (0.3 mg/kg IV), suggesting the carotid body is a/the major locus of action. Electrophysiology studies, in isolated Type I cells, established that GAL-021 (30 μM) and GAL-160 (30 μM) inhibited the BK(Ca) current without affecting the delayed rectifier K(+), leak K(+) or inward Ca(2+) currents. At a higher concentration of GAL-160 (100 μM), inhibition of the delayed rectifier K(+) current and leak K(+) current were observed. These data are consistent with the concept that GAL-021 and GAL-160 influence breathing control by acting as peripheral chemoreceptor modulators predominantly by inhibiting BK(Ca) mediated currents in glomus cells of the carotid body.

Deep transverse metatarsal ligament and static stability of lesser metatarsophalangeal joints: a cadaveric study.

The static support that guides motion around the lesser metatarsophalangeal joints (MTPJs) is complex. Biomechanical studies revealed important roles of both the plantar plane and collateral ligaments. Since part of the plantar plate is attached to the deep transverse metatarsal ligament (DTML), we hypothesized that the transection of the DTML in the intermetatarsal space may substantially reduce the MTPJ stability. The second, third, and fourth MTPJ stabilities of 6 fresh-frozen human cadaveric foot specimens were measured under load control. Both dorsiflexion and dorsal subluxation conditions were tested. After the intact condition was assessed, the DTML was sequentially transected such that each MTPJ had a unilateral and then a bilateral DTML transection. Stiffness data were calculated using the loading range in each test condition. Paired Student t tests were performed to test for statistical significance (P value less than .05). In intact specimens, the mean stiffness with dorsiflexion of the second, third, and fourth toes was 0.52 ± 0.15 N/deg. When the DTML was operatively transected on one side, the dorsiflexion stiffness significantly decreased 17.3% to an average of 0.43 ± 1.00 N/deg (P < .001). Subsequent transection of the DTML on the other side of each joint resulted in a further significant decrease of 5.8% to an average of 0.40 ± 0.08 N/deg (P < .001). The mean stiffness with dorsal subluxation of the intact second, third, and fourth toes was 3.55 ± 0.66 N/mm. When the DTML was operatively transected on one side, the dorsal subluxation stiffness significantly decreased 16.1% to an average of 2.98 ± 0.64 N/mm (P < .001). Subsequent transection of the DTML on the other side of each joint resulted in a further significance decrease of 7.6% to an average of 2.71 ± 0.48 N/mm (P = .016). The DTML has a significant role in maintaining lesser MTPJ ligament stability. Both unilateral and bilateral DTML transections caused substantial instability of the lesser MTPJ. The DTML is part of the natural static restraint to dorsiflexion or dorsal subluxation of the lesser MTPJ. Operative transection, injury, or degeneration of this ligament may predispose the adjacent MTPJ to instability.

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy.

Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to phosphodiesterase 5 inhibitors, which act downstream of cavernous nerve (CN)-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. This study aimed to determine if topically applied NO-releasing nanoparticles (NO-NPs) could elicit erections in a rat model of RP through increased blood flow. Twenty-six Sprague Dawley rats underwent bilateral transection of the CN. One week later, NO-NPs were applied topically to the penile shaft in dimethylsulfoxide (DMSO) gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty NPs. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-NPs on blood flow was determined using a hamster dorsal window chamber. Animals were investigated for spontaneous erections, onset and duration of erectile response, and basal ICP/BP ratio. Microcirculatory blood flow was determined through measurements of arteriolar and venular diameter and red blood cell velocity. Eight of 10 animals treated with NO-NPs suspended in DMSO gel had significant increases in basal ICP/BP, and 6 out of these 10 animals demonstrated spontaneous erections of approximately 1 minute in duration. Time to onset of spontaneous erections ranged from 5 to 37 minutes, and they occurred for at least 45 minutes. Similar results were observed with NO-NPs applied in coconut oil. No erectile response was observed in control animal models treated with empty NPs. The hamster dorsal window chamber experiment demonstrated that NO-NPs applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Topically applied NO-NPs induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that NO-NPs would be useful in penile rehabilitation of patients following RP.

Restoration from acute urinary dysfunction using Utah electrode arrays implanted into the feline pudendal nerve.

To investigate intrafascicular pudendal nerve stimulation in felines as a means to restore urinary function in acute models of urinary incontinence, overactive bladder, and underactive bladder. Felines were anesthetized, and high-electrode-count (48 electrodes; 25 electrodes/mm(2) ) electrode arrays were implanted intrafascicularly into the pudendal nerve trunk. Electrodes were mapped for their ability to selectively or nonselectively excite the external anal sphincter, external urethral sphincter, and the detrusor bladder muscle. Statistical analysis was carried out to quantify reflexive voiding efficiencies, mean impedances of the microelectrodes used in this study, and to determine what differences, if any, in bladder contraction amplitudes were evoked by different electrode configurations. Multielectrode arrays implanted into the pudendal nerve trunk were able to selectively and nonselectively excite genitourinary muscles. After inducing urinary incontinence with bilateral pudendal nerve transections (proximal to the implants), electrical stimulation delivered through certain microelectrodes was able to significantly reduce leaking (p = 0.008). Electrical stimulation delivered through detrusor selective electrodes was able to inhibit reflexive bladder contractions and excite bladder contractions, depending on the stimulation frequency. Specific electrode configurations were able to drive significantly (p < 0.001) larger bladder contractions than other electrode configurations, depending on the preparation. Successful reflexively or electrically driven bladder contractions were achieved in 46% and 38% of the preparations, respectively, an observation that has not been noted in previously published feline pudendal stimulation studies. Multielectrode arrays implanted intrafascicularly into the pudendal nerve trunk may provide a promising new clinical neuromodulation therapy for the restoration of urinary function.

Motor function of the upper-extremity after transection of the second thoracic nerve root during total en bloc spondylectomy.

BackgroundIn total en bloc spondylectomy (TES) of upper thoracic spine including the second thoracic (T2) vertebra, T2 nerve roots are usually transected. In this study, we examined the association between transection of the T2 nerve roots and upper-extremity motor function in patients with upper thoracic TES.MethodsWe assessed 16 patients who underwent upper thoracic TES with bilateral transection of the T2 nerve roots. Patients were divided into three groups: 3 patients without any processing of T1 and upper nerve roots (T2 group), 7 with extensive dissection of T1 nerve roots (T1–2 group), and 6 with extensive dissection of T1 and upper nerve roots (C–T2 group). Postoperative upper-extremity motor function was compared between the groups.ResultsPostoperative deterioration of upper-extremity motor function was observed in 9 of the 16 patients (56.3%). Three of the 7 patients in the T1–2 group and all 6 patients in the C–T2 group showed deterioration of upper-extremity motor function, but there was no deterioration in the T2 group. In the T1–2 group, 3 patients showed mild deterioration that did not affect their activities of daily living and they achieved complete recovery at the latest follow-up examination. In contrast, severe dysfunction occurred frequently in the C–T2 group, without recovery at the latest follow-up.ConclusionsThe transection of the T2 nerve roots alone did not result in upper-extremity motor dysfunction; rather, the dysfunction is caused by the extensive dissection of the T1 and upper nerve roots. Therefore, transection of the T2 nerve roots in upper thoracic TES seems to be an acceptable procedure with satisfactory outcomes.

Bilateral intracranial EEG with corpus callosotomy may uncover seizure focus in nonlocalizing focal epilepsy

PurposeTo evaluate the value of a new multi-stage surgical procedure using bilateral intracranial electroencephalogram (iEEG) prior and post complete corpus callosotomy (CC) for epileptogenic focus localization. MethodThirty patients with drug-resistant epilepsy underwent bilateral iEEG monitoring to localize epileptogenic focus for surgical treatment. Among them, bisynchronous epileptogenic activities were found in 9 pediatric patients. These 9 patients then received complete CC and continued bilateral iEEG monitoring for further seizure localization. Final surgical treatment decisions were made based on the bilateral iEEG findings post complete CC. The entire multi-stage procedure was performed during the same hospital stay. We retrospectively studied the data from the 9 patients. ResultsSeizure onset was lateralized in 3 patients who later received functional hemispherectomy. In another 4 patients, seizure onset was localized, resulting in resective surgery. Bilateral multiple subpial transection was performed on 1 patient with identified bilateral independent seizure onset. One patient did not have seizures following complete CC leading to removal of electrodes without any further resection. Subsequent follow-up showed favorable outcome in all patients: seizure-free in 7, more than 90% reduction in 2. None of the patients experienced surgery related complications during the procedure and follow-up period. ConclusionThe multi-stage surgical procedure utilizing iEEG monitoring with CC is a viable option for select patients with catastrophic non-localizing epilepsy. Further study is necessary to find the optimal selection criteria for use of this novel approach.

Bladder Reinnervation Using a Primarily Motor Donor Nerve (Femoral Nerve Branches) is Functionally Superior to Using a Primarily Sensory Donor Nerve (Genitofemoral Nerve)

We determined whether transfer of a primarily motor nerve (femoral) to the anterior vesicle branch of the pelvic nerve would allow for more effective bladder reinnervation than transfer of a primarily sensory nerve (genitofemoral). A total of 41 female mongrel dogs underwent bladder decentralization and then bilateral nerve transfer, or served as sham operated or unoperated controls. Decentralization was achieved by bilateral transection of all sacral roots that induced bladder contraction upon electrical stimulation. Retrograde neuronal labeling dye was injected in the bladder 3 weeks before sacrifice. Increased detrusor pressure after direct stimulation of the transferred nerve, lumbar spinal cord or spinal root was observed in 12 of 17 dogs with genitofemoral nerve transfer and in 9 of 10 with femoral nerve transfer (mean ± SEM 7.6 ± 1.4 and 11.7 ± 3.1 cm H2O, respectively). Mean detrusor pressure after direct electrical stimulation of transferred femoral nerves was statistically significantly greater than after stimulation of transferred genitofemoral nerves. Retrograde labeled neurons from the bladder observed in upper lumbar cord segments after genitofemoral and femoral nerve transfer confirmed bladder reinnervation, as did labeled axons at the nerve transfer site. While transfer of a mixed sensory and motor nerve (genitofemoral) or a primarily motor nerve (femoral) can reinnervate the bladder, using the primarily motor nerve provided greater return of nerve evoked detrusor contraction. This surgical approach may be useful to achieve bladder emptying in patients with lower motor spinal cord injury.

Essential role of hemoglobin beta-93-cysteine in posthypoxia facilitation of breathing in conscious mice

When erythrocyte hemoglobin (Hb) is fully saturated with O2, nitric oxide (NO) covalently binds to the cysteine 93 residue of the Hb β-chain (B93-CYS), forming S-nitrosohemoglobin. Binding of NO is allosterically coupled to the O2 saturation of Hb. As saturation falls, the NO group on B93-CYS is transferred to thiols in the erythrocyte, and in the plasma, forming circulating S-nitrosothiols. Here, we studied whether the changes in ventilation during and following exposure to a hypoxic challenge were dependent on erythrocytic B93-CYS. Studies were performed in conscious mice in which native murine Hb was replaced with human Hb (hB93-CYS mice) and in mice in which murine Hb was replaced with human Hb containing an alanine rather than cysteine at position 93 on the Bchain (hB93-ALA). Both strains expressed human γ-chain Hb, likely allowing a residual element of S-nitrosothiol-dependent signaling. While resting parameters and initial hypoxic (10% O2, 90% N2) ventilatory responses were similar in hB93-CYS mice and hB93-ALA mice, the excitatory ventilatory responses (short-term potentiation) that occurred once the mice were returned to room air were markedly diminished in hB93-ALA mice. Further, short-term potentiation responses were virtually absent in mice with bilateral transection of the carotid sinus nerves. These data demonstrate that hB93-CYS plays an essential role in mediating carotid sinus nerve-dependent short-term potentiation, an important mechanism for recovery from acute hypoxia.

Concentration and state dependent reductions in corn oil intakes after glossopharyngeal nerve transections in rats

Previous studies indicate a role for the glossopharyngeal nerve (GL) in the detection of dietary fats. The present experiments examined the effects of bilateral glossopharyngeal nerve transections (GLx) on the intake of low (4.8%), moderate (16%), and full-fat (100%) corn oil in non-deprived, food-deprived, and water-deprived rats. The rats had access to oils, 0.3M sucrose, and water in a gustometer that measured number of licks and latency to the first lick during brief access trials. The behavioral measures were used as indices of the amount consumed and the motivation to ingest, respectively. After baseline intakes had stabilized, the rats received GLx or sham transections (Sham) and were then re-tested. Pre and post-surgery responses were compared to determine the impact of GLx on intake and the motivation to ingest. In non-deprived rats, GLx reduced the intake of 4.8% and 16% oils and decreased the motivation to ingest these oils. In food-deprived rats, GLx prevented increases in the ingestion of 4.8% and 16% oils and in the motivation to ingest these oils. In water-deprived rats, GLx reduced the intake of 100% oil and produced a general decrease in the motivation to consume low, moderate, and full-fat emulsions. These results indicate that GL is partially involved in corn oil intake and suggest an interactive effect of oil concentration with homeostatic state.

Effects of gustatory nerve transection and/or ovariectomy on oral capsaicin avoidance in rats

The incidence of chronic oral pain such as burning mouth syndrome is greater in peri-menopausal females, and was postulated to be associated with gustatory nerve damage. We investigated whether bilateral transection of the chorda tympani, with or without accompanying ovariectomy, affected oral capsaicin avoidance in rats. Female rats had restricted access to 2 bottles, 1 bottle containing capsaicin (concentration range: 0.33–33μM/L) and the other vehicle. Percent volume of capsaicin consumption and lick counts were measured. The concentration series was tested before and 0.5, 3, 6, 9, and 12months after the following surgical procedures: (a) bilateral transection of the chorda tympani (CTx); (b) ovariectomy (OVx); (3) CTx plus OVx; or (4) sham CT surgery. Before surgery there was a concentration-dependent decrease in licks and volume of capsaicin consumed, with a threshold between 0.1 and 0.3ppm. The majority of drink licks occurred during the first 9minutes of access. Over the 12-month test period, the CTx group did not exhibit reduced capsaicin consumption, and consumed significantly more capsaicin at 6 and 9months postsurgery. Rats in the OVx group consistently consumed significantly less capsaicin and exhibited significantly higher counts of capsaicin-evoked Fos-like immunoreactivity in the dorsomedial trigeminal subnucleus caudalis (Vc) compared to all other treatment groups. That CTx, with or without OVx, did not enhance capsaicin avoidance indicates that damage to the gustatory system does not disinhibit trigeminal nociceptive transmission.

Sensory input is required for callosal axon targeting in the somatosensory cortex

BackgroundSensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex.ResultsEliminating sensory input to either hemisphere by unilateral transection of infraorbital nerve (ION) prevents target selection of callosal axons in contralateral cortex. Strikingly, blocking sensory input bilaterally, by simultaneously transecting both IONs, results in rescued callosal projection. In contrast, non-simultaneous bilateral ION transection has the same effect as unilateral transection. Similar results are obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain slices treated with KCl is decreased more in contralateral cortex with unilateral removal of sensory input, but decreased similarly in both cortices in mice with simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical neurons is also reduced in contralateral cortex with the unilateral removal of sensory input, but equally reduced on both sides with the bilateral removal of sensory input, suggesting that unbalanced bilateral sensory input might lead to mismatched neuronal activity between the two cortices and contribute to the formation of callosal projection.ConclusionOur data demonstrate a critical role of balanced bilateral somatosensory input in the formation of callosal connections, and thus reveal a new role of sensory input in wiring brain circuits.

Abstract 18030: Electrophysiological Effects of Efferent and Afferent Right and Left Vagal Nerve Stimulation on Regional Ventricular Myocardial Repolarization

BACKGROUND: Vagal nerve stimulation (VNS) is thought to be cardioprotective and decreases ventricular arrhythmias. Regional ventricular electrophysiological differences of left and right and afferent vs. efferent VNS are unclear. The purpose of this study was to evaluate effects of right vs. left and afferent vs. efferent VNS on ventricular repolarization. METHODS: In 8 pigs, the heart, bilateral cervical vagus nerves, and stellate ganglia were exposed. A 56 electrode sock was placed on the ventricles and used to record activation recovery interval (ARI), a marker of action potential duration. ARIs were obtained at baseline and during intact left and right VNS. Further, ARIs were analyzed with afferent (proximal end) or efferent (distal end) VNS under 3 conditions: 1) contralateral vagus intact 2) bilateral vagal transection and 3) bilateral vagal nerve transection plus stellectomy. A Millar conductance catheter was used to record hemodynamics. RESULTS: Intact and efferent left and right VNS decreased heart rate, blood pressure, and dp/dt, P&lt;0.05 for all parameters. Intact and efferent VNS increased ARI by 49±20 ms (right intact), 45±16 ms (left intact), 46±15 ms (right efferent), and 36±8 ms (left efferent), P&lt;0.05 for all conditions vs. baseline. No significant regional differences in ARI were found with efferent VNS. Transection of the contralateral vagus nerve did not alter the effects of ipsilateral efferent VNS (403±36 ms vs. 396±31 ms, P=NS). Afferent VNS had no significant influence on ventricular ARI, with contralateral vagus nerve intact (from 365±27 ms to 373±28 ms, P=NS) or transected (from 354±25 ms to 346±27 ms, P=NS). Stellectomy reduced the impact of efferent VNS (412±26 ms pre vs. 382±25 ms post stellectomy, P&lt;0.05). CONCLUSIONS: Unlike left and right sympathetic innervation, epicardial vagal innervation is uniform without significant regional differences. Effects of efferent VNS are diminished by sympathectomy. Afferent VNS had no impact on ARI.

Chondroprotective effects of high-molecular-weight cross-linked hyaluronic acid in a rabbit knee osteoarthritis model

We hypothesized that high-molecular-weight (MW) cross-linked (CL) hyaluronic acid (HA) improves joint lubrication and has an enhanced chondroprotective effect. We examined the histopathological changes and friction coefficients in osteoarthritic knee joints after injecting high-MW CL HA. A bilateral anterior cruciate ligament transection (ACLT) model in 20 Japanese white rabbits was used. From week 5 after transection, low-MW HA (0.8×10(6)Da; HA80) or high-MW CL HA (6×10(6)Da; HA600) was injected weekly into 10 right knee for 3 weeks; normal saline (NS) was injected into the 10 left knee. A sham operation was undertaken to exclude spontaneous osteoarthritis (OA) in five knees. Results were evaluated with macroscopy, histopathology (Kikuchi's score), biomechanical testing, and rheological assessment of the joint fluid viscoelasticity. Statistical analysis was performed using one-way analysis of variance with a 95% confidence interval (CI) (P<0.05). The macroscopic findings showed severely damaged cartilage in 30% of the NS group and 20% of the HA80 and HA600 groups and intact cartilage in 100% of the sham group. The histological scores and friction coefficients of the HA600 group were significantly lower than those of the NS group (P=0.007 and P=0.002, respectively). Viscoelasticity measurements of the joint fluid showed no significant differences between the three treatment groups. High-MW CL HA exerts potential chondroprotective effects and produces superior friction coefficients. Our results suggest that HA600 delays the progression of OA effectively and improves joint lubrication significantly.

Disruption of oral sensory relay to brain increased anxiety- and depression-like behaviours in rats

ObjectiveSensory information plays an important role to determine psycho-emotional behaviours of individuals. Lingual nerve can be damaged by dental surgery or trauma, such as physical irritation, radiation, chemotherapy, or viral infection. This study was conducted to examine the psycho-emotional effects of lingual nerve damage in which oral sensory relay to the brain is disrupted. DesignMale Sprague-Dawley rats were tested for anxiety and depression-related behaviours after bilateral transections of the lingual and chorda tympani nerves (Nx) or sham operation. Tissue contents of serotonin and its metabolite in the hippocampus, hypothalamus, and nucleus accumbens were analyzed by high-performance liquid chromatography. ResultsSucrose preference was reduced in Nx rats compared with sham rats, suggesting the development of anhedonia, decreased pleasure seeking behaviour, by the lingual nerves transection. Ambulatory activity was decreased, anxiety-related behaviours during the activity test increased, time spent in the open arms during elevated plus maze test decreased, and immobility duration during forced swim test increased in Nx rats compared with sham rats. Serotonin level in the hippocampus of Nx rats was decreased significantly compared with sham rats. ConclusionsResults suggest that aberration of oral sensory relay to brain may lead to the development of depression- and anxiety-related disorders, and decreased serotonergic neurotransmission in the hippocampus may play a role in its underlying mechanism.

Postoperative occipital neuralgia with and without C2 nerve root transection during atlantoaxial screw fixation: a post-hoc comparative outcome study of prospectively collected data

Background contextAlthough routine transection of the C2 nerve root during atlantoaxial segmental screw fixation has been recommended by some surgeons, it remains controversial and to our knowledge no comparative studies have been performed to determine whether transection or preservation of the C2 nerve root affects patient-derived sensory outcomes. PurposeThe purpose of this study is to specifically analyze patient-derived sensory outcomes over time in patients with intentional C2 nerve root transection during atlantoaxial segmental screw fixation compared with those without transection. Study designThis is a post-hoc comparative analysis of prospectively collected patient-derived outcome data. Patient sampleThe sample consists of 24 consecutive patients who underwent intentional bilateral transection of the C2 nerve root during posterior atlantoaxial segmental screw fixation (transection group) and subsequent 41 consecutive patients without transection (preservation group). Outcome measuresA visual analog scale (VAS) score was used for occipital neuralgia as the primary outcome measure and VAS score for neck pain, neck disability index score and Japanese Orthopedic Association score for cervical myelopathy and recovery rate, with bone union rate as the secondary outcome measure. MethodsPatient-derived outcomes including change in VAS score for occipital neuralgia over time were statistically compared between the two groups. This study was not supported by any financial sources and there is no topic-specific conflict of interest related to the authors of this study. ResultsSeven (29%) of the 24 patients in the transection group experienced increased neuralgic pain at 1 month after surgery either because of newly developed occipital neuralgia or aggravation of preexisting occipital neuralgia. Four of the seven patients required almost daily medication even at the final follow-up (44 and 80 months). On the other hand, only four (10%) of 41 patients in the preservation group had increased neuralgic pain at 1 month after surgery, and at ≥1 year, no patients had increased neuralgic pain. The difference in the prevalence of increased neuralgic pain between the two groups was statistically significant at all time points (3, 6, 12, and 24 months postoperatively) except at 1 month postoperatively. The intensity of neuralgic pain, which preoperatively had not been significantly different between the two groups, was significantly higher in the transection group at the final follow-up. ConclusionsC2 nerve root transection is not a benign procedure and, in our experience, more than a quarter of the patients experience increased neuralgic pain following C2 nerve root transection. Because the prevalence and intensity of postoperative neuralgia was significantly higher with C2 nerve root transection than with its preservation, we recommend against routine C2 nerve root transection when performing atlantoaxial segmental screw fixation.

Only repeated administration of the serotonergic agonist 8-OH-DPAT improves place learning of rats subjected to fimbria-fornix transection

Serotonergic agonists may act neuroprotectively against brain injury. This study addressed the therapeutic potential of 8-hydroxy-2-di-n-propylamino-tetralin (8-OH-DPAT), a selective 5-HT1A/7 receptor agonist, after mechanical brain injury, and evaluated its effects in terms of acquisition of an allocentric place learning task in a water maze. Rats were divided into 6 experimental groups, three of which were subjected to bilateral transection of fimbria-fornix (FF), while three groups were given control surgery (Sham). After surgery, within both the lesioned, and sham-operated animals, respectively, one group was administered a single dose of saline, one group was given a single dose (0.5mg/kg/b.w.) of 8-OH-DPAT, and one group was treated with daily administration of 8-OH-DPAT (0.5mg/kg/b.w.) for eight days. The acquisition of the water maze based place learning task started on the 8th day post-surgery and continued for 20days. The results show that the lesioned group subjected to repeated administration of 8-OH-DPAT demonstrated a significantly improved acquisition of the place learning task compared to the vehicle injected lesion group. In contrast, the lesioned group treated with a single administration displayed impaired performance compared to the baseline lesion group. There were no significant effects of the 8-OH-DPAT administration in the sham control groups. We conclude that only the repeated stimulation of the 5-HT1A/7 system was associated with beneficial, recovery enhancing effects.

Lateral reticular nucleus modulates the cardiosomatic reflex evoked by intrapericardial capsaicin in the rat

The current study examined the role of the lateral reticular nucleus (LRN) in modulating the cardiosomatic reflex (CSR) induced by intrapericardial capsaicin in the anesthetized rat. Intrapericardial capsaicin was administered, and the CSR was monitored via electromyogram responses of the dorsal spinotrapezius muscle. Electrical stimulation of the LRN (10, 20 and 30μA) depressed the CSR induced by intrapericardial capsaicin in an intensity-dependent manner. Microinjection of glutamate (4, 10, 20 and 40nmol, in 0.2μL) into the LRN replicated the effects of electrical stimulation. Furthermore, bilateral transections of the dorsolateral funiculus (DLF) decreased the LRN electrical stimulation-induced inhibition of the electromyogram responses. Intrathecal administration of the α2 -adrenergic receptor antagonist yohimbine or the serotonergic receptor antagonist methysergide significantly attenuated the LRN electrical stimulation-induced inhibition of the electromyogram responses. However, intrathecal application of the opioid receptor antagonist naloxone had no effect on the LRN electrical stimulation-induced inhibition. These results suggest that the LRN-DLF-spinal cord pathway is involved in descending inhibition of the CSR, and spinal α2 -adrenergic and serotonergic receptors participate in this descending inhibition.

Schwann cell‐mediated delivery of glial cell line‐derived neurotrophic factor restores erectile function after cavernous nerve injury

To evaluate the time-course of functional recovery after cavernous nerve injury using glial cell line-derived neurotrophic factor-transduced Schwann cell-seeded silicon tubes. Sections of the cavernous nerves were excised bilaterally (5 mm), followed by immediate bilateral surgical repair. A total of 20 study nerves per group were reconstructed by interposition of empty silicon tubes and silicon tubes seeded with either glial cell line-derived neurotrophic factor-overexpressing or green fluorescent protein-expressing Schwann cells. Control groups were either sham-operated or received bilateral nerve transection without nerve reconstruction. Erectile function was evaluated by relaparotomy, electrical nerve stimulation and intracavernous pressure recording after 2, 4, 6, 8 and 10 weeks. The animals underwent re-exploration only once, and were killed afterwards. The nerve grafts were investigated for the maturation state of regenerating nerve fibers and the fascular composition. Recovery of erectile function took at least 4 weeks in the current model. Glial cell line-derived neurotrophic factor-transduced Schwann cell grafts restored erectile function better than green fluorescent protein-transduced controls and unseeded conduits. Glial cell line-derived neurotrophic factor-transduced grafts promoted an intact erectile response (4/4) at 4, 6, 8 and 10 weeks that was overall significantly superior to negative controls (P < 0.001). Maximum intracavernous pressure on electrostimulation was significantly elevated using glial cell line-derived neurotrophic factor-transduced grafts compared with negative controls (P = 0.018) and unseeded tubes (P = 0.034). Return of function was associated with the electron microscopic evidence of preganglionic myelinated nerve fibers and postganglionic unmyelinated axons. Schwann cell-mediated delivery of glial cell line-derived neurotrophic factor presents a viable approach for the treatment of erectile dysfunction after cavernous nerve injury.