Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

Photobiomodulation and Vascularization in Conduit-Based Peripheral Nerve Repair: A Narrative Review.

Background: Peripheral nerve injuries pose a significant clinical issue for patients, especially in the most severe cases wherein complete transection (neurotmesis) results in total loss of sensory/motor function. Nerve guidance conduits (NGCs) are a common treatment option that protects and guides regenerating axons during recovery. However, treatment outcomes remain limited and often fail to achieve full reinnervation, especially in critically sized defects (>3 cm) where a lack of vascularization leads to neural necrosis. Conclusions: A multitreatment approach is, therefore, necessary to improve the efficacy of NGCs. Stimulating angiogenesis within NGCs can help alleviate oxygen deficiency through rapid inosculation with the host vasculature, whereas photobiomodulation therapy (PBMT) has demonstrated beneficial therapeutic effects on regenerating nerve cells and neovascularization. In this review, we discuss the current trends of NGCs, vascularization, and PBMT as treatments for peripheral nerve neurotmesis and highlight the need for a combinatorial approach to improve functional and clinical outcomes.

Effect of delayed photobiomodulation therapy on neurosensory recovery in patients with mandibular nerve neurotmesis following traumatic mandibular fracture: A randomized triple-blinded clinical trial.

INTRODUCTION: There is a possibility of neurotmesis of the inferior alveolar nerve (IAN) in mandibular fractures, which leads to neurosensory impairment. In this study, we aimed to investigate the efficacy of photobiomodulation therapy (PBMT) in patients with neurotmesis following trauma and mandibular fracture. MATERIALS AND METHODS: This triple-blind randomized trial was carried out on patients who suffered neurotmesis of the IAN following mandibular angle and body fracture at least for 6 months. In the intervention group, laser irradiation was applied with a low-level GaAlAs diode laser (continuous wave of 810 nm wavelength, power of 200 mW, and energy density of 12-14 J/cm2). In the control group, the laser probe was turned off and placed on the affected area. LLLT was done for 12 sessions (2 times/week for 6 weeks). Light touch sensations, two-point discrimination, thermal discrimination (cold and warm stimulus), electric pulp test (EPT), and oral health impact profile (OHIP)-14 questionnaire were performed before the intervention, immediately after each PBMT session, and after 3, 6, 9 and 12 months. RESULTS: In both groups, 3 and 23 patients were female and male, respectively. The results showed significantly improved light (cotton swab), light (wooden cotton swab), and sharp (dental needle) touch sensations, and two-point discrimination test in the PBMT group after the 10th, 11th, 10th, and 10th session, respectively. Two-way repeated measure ANOVA revealed that the trend of light touch sensation with cotton swab and two-point discrimination test was statistically significant (p-value = 0.002 and 0.001, respectively). The results of OHIP-14 test showed a significantly higher mean in the PBMT group 3 months after PBMT. There was no statistically significant difference in EPT and thermal discrimination tests regarding the patients' group. CONCLUSION: PBMT could be an effective treatment for late post-traumatic nerve neurotmesis following a traumatic mandibular fracture.

Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated. AIMS: To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP. METHODS: Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-ß1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN. OUTCOMES: Effects of LIES on EF, erectile tissue remodeling and CN structure. RESULTS: EF was decreased (P < .05) 7 days after BCNI and increased (P < .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P < .05) after BCNI and normalized by LIES. Protein expressions of TGF-ß1, IL-6, and CRP were increased in the penis (P < .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P < .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P < .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P < .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P < .05) after BCNI and decreased (P < .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups. CLINICAL TRANSLATION: LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery. STRENGTHS & LIMITATIONS: This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required. CONCLUSION: This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686-696.

Effects of Photobiomodulation Therapy (LED 630 nm) on Muscle and Nerve Histomorphometry after Axonotmesis.

Peripheral injuries constitute a substantial clinical problem with unsatisfactory treatment. The study's objective was to analyze the effects of photobiomodulation therapy (PBMT) on median nerve regeneration and muscle recovery after axonotmesis. Twenty-four rats were randomized into three groups: control (CG), injury (IG), and LED therapy (LEDG). A 630 ± 20 nm (300-mW) LED was placed in contact with the skin. One point over the injury site was irradiated for 30 s, delivering 9 J (9 J cm-2 ). PBMT irradiation was performed once daily for 5 days followed by two-day interval and then more five consecutive days of treatment. Proximal and distal segments of the nerve and flexors muscles were removed for histomorphometric analysis using H&E staining for muscles and osmium tetroxide for nerves. The myelinated fiber and axon diameter and the myelin sheath thickness were greater in the proximal and distal nerve segments in the LEDG compared to the IG (P ≤ 0.05). The number of myelinated fibers was greater in the distal segment of the LEDG (P ≤ 0.05). The area, circumference, and diameter of the muscle fibers were larger in the LEDG than in the IG (P ≤ 0.05). The PBMT protocol used favored axonal regeneration and muscle recovery.

Novel Concept Enabling an Old Idea: A Flexible Electrode Array to Treat Neurogenic Erectile Dysfunction.

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.

An Overview of Culinary and Medicinal Mushrooms in Neurodegeneration and Neurotrauma Research.

Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.

Nutritional and Bioenergetic Considerations in Critically Ill Patients with Acute Neurological Injury.

The brain, due to intensive cellular processes and maintenance of electrochemical gradients, is heavily dependent on a constant supply of energy. Brain injury, and critical illness in general, induces a state of increased metabolism and catabolism, which has been proven to lead to poor outcomes. Of all the biochemical interventions undertaken in the ICU, providing nutritional support is perhaps one of the most undervalued, but potentially among the safest, and most effective interventions. Adequate provisions of calories and protein have been shown to improve patient outcomes, and guidelines for the nutritional support of the critically ill patient are reviewed. However, there are no such specific guidelines for the critically ill patient with neurological injury. Patients with primary or secondary neurological disorders are frequently undernourished, while data suggest this population would benefit from early and adequate nutritional support, although comprehensive clinical evidence is lacking. We review the joint recommendations from the Society for Critical Care Medicine and the American Society for Parenteral and Enteral Nutrition, as they pertain to neurocritical care, and assess the recommendations for addressing nutrition in this patient population.

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures. The effects of phosphodiesterase type 4 inhibitor (PDE4I) and PDE5I on neuronal cell survival were evaluated. Male rats underwent BCNI and were untreated (BCNI), immediately treated with application of empty NSPs (BCNI + NSP), NSPs containing sildenafil (Sild + NSP), or NSPs containing rolipram (Rol + NSP). MAIN OUTCOME MEASURES: Viability of neuronal cells was measured. Intracavernous pressure changes after cavernous nerve electrostimulation and expression of neurofilament, nitric oxide synthase, and actin in mid-shaft of penis were analyzed 14 days after injury. RESULTS: Sildenafil and rolipram significantly decreased cell death after exposure to H2O2 and hypoxia in PC12, SH-SY5Y, and NT2 cells. PC12 cells did not express PDE5 and knockdown of PDE4 significantly increased cell viability in PC12, SH-SY5Y, and NT2 cells exposed to hypoxia. The ratio of intracavernous pressure to mean arterial pressure and expression of penile neurofilament, nitric oxide synthase, and actin were significantly higher in the Sild + NSP and Rol + NSP groups than in the BCNI and BCNI + NSP groups. Limitations included analysis in only two PDE families using only a single dose. CONCLUSION: Sildenafil showed the most profound neuroprotective effect compared with tadalafil and vardenafil. Sildenafil- or rolipram-loaded NSP delivery to the site of nerve injury prevented erectile dysfunction and led to increased neurofilament, nitric oxide synthase, smooth muscle content in rat penile tissue after BCNI.

Advanced and High-Throughput Method for Mitochondrial Bioenergetics Evaluation in Neurotrauma.

Mitochondrial dysfunction is one of the key posttraumatic neuropathological events observed in various experimental models of traumatic brain injury (TBI). The extent of mitochondrial dysfunction has been associated with the severity and time course of secondary injury following brain trauma. Critically, several mitochondrial targeting preclinical drugs used in experimental TBI models have shown improved mitochondrial bioenergetics, together with cortical tissue sparing and cognitive behavioral outcome. Mitochondria, being a central regulator of cellular metabolic pathways and energy producer of cells, are of a great interest for researchers aiming to adopt cutting-edge methodology for mitochondrial bioenergetics assessment. The traditional way of mitochondrial bioenergetics analysis utilizing a Clark-type oxygen electrode (aka. oxytherm) is time-consuming and labor-intensive. In the present chapter, we describe an advanced and high-throughput method for mitochondrial bioenergetics assessments utilizing the Seahorse Biosciences XF(e)24 Flux Analyzer. This allows for simultaneous measurement of multiple samples with higher efficiency than the oxytherm procedure. This chapter provides helpful guidelines for conducting mitochondrial isolation and studying mitochondrial bioenergetics in brain tissue homogenates following experimental TBI.

Impact of Tissue Sealing Sheet on Erectile Dysfunction in a Rat Model of Nerve-Sparing Radical Prostatectomy.

INTRODUCTION: The tissue sealing sheet has recently been used to prevent intraoperative bleeding from the neurovascular bundles in radical prostatectomy. Surgical stress or inflammatory changes likely play a role in erectile dysfunction after cavernous nerve injury. However, the efficacy of a tissue sealing sheet for preventing erectile function after nerve-sparing radical prostatectomy remains unclear. AIM: To evaluate the effect of a tissue sealing sheet on erectile dysfunction after cavernous nerve dissection. METHODS: Male Sprague-Dawley rats were randomly divided into three groups and subjected to sham operation or bilateral cavernous nerve dissection with (sheet group) or without (non-sheet group) a tissue sealing sheet. In the sheet group, cavernous nerves were sealed with a tissue sealing sheet immediately after cavernous nerve dissection. MAIN OUTCOME MEASURES: Erectile function was assessed by measuring intracavernous pressure and arterial pressure during pelvic nerve electrostimulation at 4 weeks after surgery. Expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 in the major pelvic ganglion were examined by real-time polymerase chain reaction. RESULTS: Mean intracavernous pressure along with mean arterial pressure in the sheet group were similar to those in the sham group and showed a significant positive response compared with the non-sheet group (P < .05). Furthermore, expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 were significantly lower in the sheet group than in the non-sheet group (P < .05). CONCLUSION: Use of a tissue sealing sheet attenuated postoperative inflammatory changes and oxidative stress and improved erectile function after cavernous nerve injury in rats. The tissue sealing sheet might become a useful therapeutic approach to preserve erectile function after nerve-sparing radical prostatectomy.

Preclinical neuroprotective actions of xenon and possible implications for human therapeutics: a narrative review.

PURPOSE: The purpose of this report is to facilitate an understanding of the possible application of xenon for neuroprotection in critical care settings. This narrative review appraises the literature assessing the efficacy and safety of xenon in preclinical models of acute ongoing neurologic injury. SOURCE: Databases of the published literature (MEDLINE® and EMBASE™) were appraised for peer-reviewed manuscripts addressing the use of xenon in both preclinical models and disease states of acute ongoing neurologic injury. For randomized clinical trials not yet reported, the investigators' declarations in the National Institutes of Health clinical trials website were considered. PRINCIPAL FINDINGS: While not a primary focus of this review, to date, xenon cannot be distinguished as superior for surgical anesthesia over existing alternatives in adults. Nevertheless, studies in a variety of preclinical disease models from multiple laboratories have consistently shown xenon's neuroprotective properties. These properties are enhanced in settings where xenon is combined with hypothermia. Small randomized clinical trials are underway to explore xenon's efficacy and safety in clinical settings of acute neurologic injury where hypothermia is the current standard of care. CONCLUSION: According to the evidence to date, the neuroprotective efficacy of xenon in preclinical models and its safety in clinical anesthesia set the stage for the launch of randomized clinical trials to determine whether these encouraging neuroprotective findings can be translated into clinical utility.

Resultados del tratamiento kinésico en un paciente con diagnóstico de neuropraxia ­ axonotmesis del plexo braquial / Results of kinesic treatment in a patient with diagnosis of neuropraxia - brachial plexus axonotmesis

Se presenta el caso de un paciente de 71 años, de sexo masculino, con diagnóstico médico de neuropraxia-axonotmesis del plexo braquial como producto de una luxación de hombro. Presentaba el brazo izquierdo pléjico luego de la reducción. Ingresó al Servicio Universitario de Kinesiología y realizó 60 sesiones de tratamiento kinésico basado en electroestimulación muscular selectiva con corriente exponencial y rectangular, asociada a ejercicios de reeducación muscular. Mediante la electroestimulación se logró prevenir la atrofia muscular, lo cual permitió desarrollar posteriormente trofismo y fuerza muscular. El paciente recuperó las funciones musculares que le permitieron realizar sus actividades de la vida diaria de manera autónoma. Este caso pertenece a un ensayo clínico controlado aprobado por el Comité de Bioética de la Facultad de Medicina

Increased expression of the neuroregenerative peptide galanin in the major pelvic ganglion following cavernous nerve injury.

INTRODUCTION: Erectile dysfunction (ED) remains a frequent complication of radical prostatectomy due to injury to the cavernous nerves (CNs). A recent microarray showed the neuropeptide galanin to be one of the most strikingly upregulated genes in the rat major pelvic ganglion (MPG) after bilateral CN crush injury (BCNI). AIM: The aim of this study is to evaluate the temporal regulation of galanin in the MPG after BCNI and its relationship to functional nerve regeneration. METHODS: Changes in galanin, galanin receptor (galR), and c-JUN mRNA expression were assessed in Sprague-Dawley rats after sham operation (n = 10) and at 48 hours (n = 10), 7 (n = 10), 14 (n = 5), 21 (n = 5), 30 (n = 5), and 60 (n = 5) days after BCNI using quantitative PCR. Erectile function was assessed by measuring intracavernous pressure (ICP) divided by mean arterial pressure (MAP) during CN electrostimulation. Immunohistochemistry was performed on the MPG in sham-operated animals and 5 days after BCNI. MAIN OUTCOME MEASURES: ICP/MAP upon CN stimulation; galanin, galR1, -2, -3, and c-JUN mRNA expression at various time points after BCNI; and nNOS, galanin, and galR distribution in the MPG of sham-operated rats and after BCNI. RESULTS: After BCNI, ICP/MAP values quickly deteriorate, while after 60 days, spontaneous restoration of erectile responses to CN stimulation is observed, reflecting CN regeneration. Galanin mRNA in the MPG is up to 186-fold upregulated compared with sham-operated rats at 48 hours and 7 days after BCNI and gradually declines with increasing time from injury, whereas galanin receptor expressions decrease and c-JUN gradually increases. Galanin expression shows a strong inverse correlation with erectile responses to CN stimulation with time from injury. Injured MPGs show a colocalization between galanin- and nNOS-positive neuronal cell population in the MPG. CONCLUSIONS: Galanin is upregulated in the MPG in the early phase after CN injury after which it gradually decreases and is present in nNOS-positive neurons of the ganglion. We hypothesize that galanin upregulation is an important factor in the endogenous neuroregenerative response to CN injury.

[Principles of early rehabilitation of the neurotrauma].

The retrospective analysis of surgical and rehabilitation treatment of 172 patients with neurotrauma was made. The patients were treated in Russian Polenov Neurosurgical Institute and Municipal hospital of St. Elizabeth in the period since 2009 till 2012. Rehabilitation of different types of neurotrauma presented the system of surgical and recovery methods of treatment, which should be used in a short term after damage. Means of internal cerebral decompression, including drainage of ecephalocoel and cerebral basal cistern and the tentoriotomy, should be used in acute period of craniocerebral trauma according to morphometric data of beam inspection. Management of wound by means of laser or LED radiation, SHWF-therapy, magnetic and electrostimulation were the effective methods of neurorehabilitation. It is noted, that 73 (43,4%) patients returned to a former employment rate among 172 victims, though 26 patients had a moderate invalidization. An average figures of Glasgow scale outcomes were 1,9+/-0,2.

Spinal cord injury and male infertility: a review / Traumatismo raquimedular e infertilidade masculina: revisão / Lesión de la médula espinal e infertilidad masculina: una revision

Spinal cord injuries remain an important factor of morbimortality in current society, involving mainly males from adolescence to adulthood. Among the sequelae caused by spinal cord injuries, the impairment of the sexual system is highly relevant since it affects the quality of sexual life and paternity. Infertility is secondary to multiple events such as erectile dysfunction, anejaculation, seminal biochemical modification and morphology of spermatozoa. Current therapies for the infertile spinal cord injured patient focus on the ejaculation stimulus followed by intrauterine insemination, leaving seminal low quality as the major factor of infertility in these patients. In this scenario, therapy with hyperbaric oxygenation, which is still being studied, represents an alternative treatment since it focuses on the central nervous system injured by the trauma and the testicular tissue in order to decrease spinal damage and to preserve the physiological regulation of the urogenital system as a form of avoiding infertility.

O trauma raquimedular (TRM) é uma importante causa de morbimortalidade na sociedade atual, principalmente por acometer adultos jovens. Dentre as diversas sequelas decorrentes da lesão medular encontram-se as alterações na qualidade de vida sexual e na paternidade. A infertilidade decorre de diversas alterações como: disfunção erétil, anejaculação, alterações bioquímicas no sêmen e estruturais nos espermatozoides. As terapias para a infertilidade pós-TRM, em geral, objetivam o estímulo à ejaculação e posterior inseminação, sendo a baixa qualidade do sêmen o fator determinante para infertilidade. A terapia hiperbárica representa uma possibilidade de atuar diretamente no tecido lesado, seja ele medular ou testicular, diminuindo o dano.

La lesión de la médula espinal sigue siendo una causa importante de morbilidad y mortalidad en la sociedad actual, que afecta principalmente a hombres en la adolescencia a la edad adulta. Entre las varias secuelas resultantes de lesiones de la médula espinal, el deterioro del sistema sexual es de gran relevancia una vez que afectan la calidad de la vida sexual y la paternidad. La infertilidad es secundaria a varios eventos, tales como la disfunción eréctil, aneyaculación, modificación bioquímica seminal y la morfología de los espermatozoides. Los tratamientos para la infertilidad post-TRM, en general, tienen por objeto estimular la eyaculación seguida de inseminación in vitro, siendo la baja calidad seminal el factor determinante de la infertilidad de estos pacientes. En este escenario, la terapia con oxigenación hiperbárica, aún en estudio, representa un tratamiento alternativo ya que actúa sobre el sistema nervioso central lesionado por el trauma y sobre el tejido testicular para reducir el daño espinal y preservar la regulación fisiológica del sistema genital como una forma de evitar la infertilidad.

Bad medicine: prescription drugs, preemption, and the potential for a no-fault fix.

For decades, federal regulation of pharmaceutical drugs and medical devices has worked hand in hand with state tort claims to protect the health and safety of the American public. Now, a new trend toward preemption endangers this scheme. In recent years, the Supreme Court has given increasing deference to agency assertions about their preemptive authority and has found preemption in an increasing number of cases. In the process, the Supreme Court has preempted claims for medical device injuries and left claims for pharmaceutical harms in a precarious position. The elimination of common law claims for drug and device harms will leave holes in the FDA's regulatory scheme, endangering the health and safety of Americans. It will also prevent ordinary Americans from seeking compensation for their injuries--even those injuries caused by manufacturer malfeasance. This Article proposes that Congress create a no-fault compensation scheme for drugs and medical devices to close these gaps. Such a scheme could be both practical and politically possible, satisfying manufacturers, tort reformers, patients, and plaintiffs' lawyers alike.

Risks, symptoms, and management of pelvic nerve damage secondary to surgery for pelvic organ prolapse: a report of 95 cases.

INTRODUCTION AND HYPOTHESIS: This study aims to report pelvic nerve damage secondary to surgical treatment of pelvic organ prolapse and the role of laparoscopy in the diagnosis and treatment of such nerve damage. METHODS: Ninety-five consecutive patients complaining of pain and/or bladder or bowel dysfunction following surgery for pelvic prolapse underwent laparoscopic exploration for pelvic neuropathy. RESULTS: A mean reduction in visual analog score (VAS) from 8.9 (± 0.96; 6-10) preoperatively to 2.9 (± 2.77; 0-6) at 1-year follow-up was obtained in patients after laparoscopic nerve decompression (n = 90; p < 0.001). Success, defined as a reduction in VAS score of greater than 50%, was obtained in 84% of patients. Sixty-five patients (68%) discontinued the regular use of analgesics. CONCLUSIONS: Because secondary nerve damage can appear months or years after the primary procedure, long-term follow-up is mandatory and should focus on nerve damage as well as anatomical and functional outcomes. Laparoscopy is a unique method for etiologic diagnosis and neurosurgical treatment of such nerve lesions through decompression or implantation of an electrode for neuromodulation.

Protective effect of GCSB-5, an herbal preparation, against peripheral nerve injury in rats.

AIM OF THE STUDY: GCSB-5 (traditional name: Chungpa-Juhn), an herbal medicine composed of 6 crude herbs (Saposhnikovia divaricata Schiskin, Achyranthis bidentata Blume, Acanthopanax sessiliflorum Seem, Cibotium baromets J. Smith, Glycine max Meriill, and Eucommia ulmoides Oliver), has been widely used in Asia for treatment of neuropathic and inflammatory diseases. This study investigated the protective effect of GCSB-5 against peripheral nerve injury in vitro and in vivo. MATERIALS AND METHODS: After left sciatic nerve transection, rats received oral administration of GCSB-5 (30, 100, 300, and 600 mg/kg), or saline (vehicle), respectively, once daily for 8 weeks. Motor functional recovery and axonal nerve regeneration were evaluated by measurement of sciatic functional index (SFI), sensory regeneration distance, and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. In the in vitro study, the effects of GCSB-5 on H(2)O(2)-induced oxidative damage in SH-SY5Y cells were investigated by measurement of cell viability, production of reactive oxygen species (ROS), lipid peroxidation, release of lactate dehydrogenease (LDH), and cellular glutathione contents. Neurite outgrowth was also determined. RESULTS: After 8 weeks of nerve transection, SFI, regeneration distance, and gastrocnemius muscle mass ratio and myelinated axon number showed a significant decrease and these decreases were attenuated by GCSB-5. GCSB-5 significantly inhibited H(2)O(2)-induced cell death and oxidative stress, as evidenced by decreases in production of ROS and lipid peroxidation and release of LDH, and by increase in total GSH content. CONCLUSIONS: The neuroprotective effect afforded by GCSB-5 is due in part to reduced oxidative stress.

Spinal cord injury: a systematic review of current treatment options.

BACKGROUND: Spinal cord injury (SCI) is a devastating event often resulting in permanent neurologic deficit. Research has revealed an understanding of mechanisms that occur after the primary injury and contribute to functional loss. By targeting these secondary mechanisms of injury, clinicians may be able to offer improved recovery after SCI. QUESTIONS/PURPOSES: In this review, we highlight advances in the field of SCI by framing three questions: (1) What is the preclinical evidence for the neuroprotective agent riluzole that has allowed this agent to move into clinical trials? (2) What is the preclinical evidence for Rho antagonists that have allowed this group of compounds to move into clinical trials? (3) What is the evidence for early surgical decompression after SCI? METHODS: We conducted a systematic review of MEDLINE and EMBASE-cited articles related to SCI to address these questions. RESULTS: As a result of an improved understanding of the secondary mechanisms of SCI, specific clinical strategies have been established. We highlight three strategies that have made their way from bench to bedside: the sodium-glutamate antagonist riluzole, the Rho inhibitor Cethrin, and early surgical decompression. Each of these modalities is under clinical investigation. We highlight the fundamental science that led to this development. CONCLUSIONS: As our understanding of the fundamental mechanisms of SCI improves, we must keep abreast of these discoveries to translate them into therapies that will hopefully benefit patients. We summarize this process of bench to bedside with regard to SCI.