Calpain Inhibition Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

INTRODUCTION: Erectile dysfunction (ED) after cavernous nerve (CN) injury remains difficult to treat. Calpain plays a critical role in causing neurodegenerative diseases. This study aimed to evaluate whether calpain inhibition preserves erectile function in a rat model of CN injury. MATERIALS AND METHODS: Rats underwent sham surgery or CN crush injury. The CN-crushed rats were treated with vehicle or MDL-28170, a specific calpain inhibitor. At 1, 2, 3, and 7 days post-surgery, major pelvic ganglia (MPG) were harvested, followed by the measurement of erectile function, respectively. At 28 days, penile tissue and distal CN were harvested, followed by the measurement of erectile function in rats. Calpain activity in MPG and corpus cavernosum, as well as TGF-ß1/Smad2 and collagen content in corpus cavernosum, were measured by western blot. Neuronal nitric oxide synthase (nNOS) was observed by immunohistochemistry. RESULTS: Increased calpain activity was observed in MPG and corpus cavernosum. CN crush markedly attenuated the erectile responses and nNOS expression in CN, and these were improved by MDL-28170 treatment. Furthermore, treatment prevented increased TGF-ß1/Smad2 and collagen expression in corpus cavernosum. CONCLUSIONS: Our results suggested that calpain activation plays a role in pathogenesis of CN injury-associated ED. Calpain inhibition could be a novel approach for preventing the development of ED following CN injury.

Incidence of pre- and postoperative urinary dysfunction associated with deep infiltrating endometriosis: relevance of urodynamic tests and therapeutic implications.

Although many series have been published on the management of digestive or urinary deep infiltrating endometriosis (DIE), few data exist on pre- and postoperative urinary dysfunction (UD) and urodynamic tests. Hence, the objective of this review was to evaluate the pre- and postoperative incidence of UD and the contribution of urodynamic tests as well as their therapeutic implications. Studies published between January 1995 and April 2012, available in the databases Medline, Embase or the Cochrane Library and responding to a key word algorithm were selected. Studies were classified according to their level of evidence in the Canadian Task Force classification. Sixty-three studies were included in this review. The incidence of preoperative UD is unknown in patients with DIE without colorectal involvement but ranges from 2% to 48% in patients with colorectal endometriosis. About half of all the patients had abnormal urodynamic test results. DIE surgery is associated with a risk of urinary dysfunction mainly corresponding to de novo voiding dysfunction in 1.4% to 29.2% of cases with a mean value of 4.8%. The rate of persistent voiding dysfunction ranges from 0 to 14.7% with a mean value of 4.6%. Risk factors of postoperative UD are the need for partial colpectomy, parametrectomy and patients requiring colo-anal anastomosis. For patients with urinary tract endometriosis, the incidence of preoperative UD is comprised between 24.4% and 79.2% with a rate of postoperative voiding dysfunction ranging from 0% to 16.9% with a mean value of 11.1%. Prevention of postoperative UD is based on nerve-sparing surgery. Treatment of voiding dysfunction requires self-catheterization. There is a lack of data on medical treatment and surgical techniques to manage postoperative UD. More effort needs to be made to detect preoperative UD associated with DIE. Preoperative evaluation by urodynamic tests and possibly electrophysiology could be of interest especially in patients with risk factors. The current review underlines the difficulties of establishing clear recommendations due to heterogeneity of the studies and the absence of a consensual definition of UD.

Galanin expression in the mouse major pelvic ganglia during explant culture and following cavernous nerve transection.

Autonomic neurons commonly respond to injury/axotomy with an increased expression of neuropeptides including galanin and pituitary adenylyl cyclase-activating polypeptide (PACAP). The increased peptide expression may enhance neuronal survival and axonal regeneration. Using quantitative (Q) PCR and immunocytochemistry, the present study tested whether galanin expression increased in male mouse major pelvic ganglia (MPG) neurons in response to injury. Galanin transcript expression increased significantly in MPG neurons following 72 h in explant culture and 72 h after unilateral transection of the cavernous nerve. Under both conditions, the increase in galanin transcript levels was greater than the increase in PACAP transcript levels. In control MPG, galanin-IR nerve fibers formed pericellular arrangements around MPG neurons although few galanin-IR cells were evident and many of the galanin-IR cells may be small intensely fluorescent (SIF) cells. In 3-day-cultured MPGs, many more galanin-IR cells and nerve fibers were noted. The increased galanin expression was most apparent in neurons that were also immunoreactive for neuronal nitric oxide synthase, rather than tyrosine hydroxylase. Some explant-cultured MPG neurons exhibited immunoreactivity to galanin and PACAP. As reported previously for PACAP, there is an injury-induced increase in MPG galanin expression, which occurs preferentially in the parasympathetic postganglionic neurons.

Pupil-sparing oculomotor nerve palsy caused by upward compression of a large posterior communicating artery aneurysm. Case report.

A 69-year-old woman without diabetes or hypertension presented with a large posterior communicating artery aneurysm projecting beneath the oculomotor nerve manifesting as a 2-week history of progressive diplopia. Neurological examination revealed external ophthalmoplegia and blepharoptosis without pupil involvement. Neuroimaging showed a large aneurysm in the left internal carotid artery projecting postero-inferiorly. Craniotomy and neck clipping of the aneurysm revealed the origin at the junction of the internal carotid artery and posterior communicating artery, and elevation of the oculomotor nerve. Pupil-sparing oculomotor nerve palsy is often assumed to be caused by ischemic injury such as hypertension and diabetes mellitus. Sometimes compressive lesion can cause pupil-sparing oculomotor nerve palsy with a short interval from the onset of symptoms to diagnosis. Despite the 2-week interval from the onset of symptoms, this patient presented with pupil-sparing oculomotor nerve palsy caused by compressive lesion. Involvement or sparing of the pupil is often considered to be the most important criterion in the diagnosis of isolated oculomotor nerve palsy. This unique case demonstrated that unusual compressive lesions must be taken into consideration in the diagnosis of pupil-sparing oculomotor nerve palsy.

Arachnoid cyst causing third cranial nerve palsy manifesting as isolated internal ophthalmoplegia and iris cholinergic supersensitivity.

An 8-month-old boy presented with anisocoria, a sluggishly reactive right pupil, and cholinergic supersensitivity as the only signs of what proved months later to be compressive third cranial nerve palsy due to an arachnoid cyst. Tonic constriction and dilation, segmental iris sphincter palsy, aberrant regeneration phenomena, ductional deficits, and ptosis were absent. The initial diagnosis was postganglionic internal ophthalmoplegia attributed to a viral ciliary ganglionopathy. Nineteen months later, he had developed an incomitant exodeviation and a supraduction deficit. Brain MRI revealed a mass consistent with an arachnoid cyst compressing the third cranial nerve in the right interpeduncular cistern. Resection of the cyst led to a persistent complete third cranial nerve palsy. This is the second reported case of prolonged internal ophthalmoplegia in a young child as a manifestation of a compressive third cranial nerve palsy. Our patient serves as a reminder that isolated internal ophthalmoplegia with cholinergic supersensitivity is compatible with a preganglionic compressive third nerve lesion, particularly in a young child.

Does the cardinal ligament of the uterus contain a nerve that should be preserved in radical hysterectomy?

The cardinal ligament (CL) of the uterus is present as a specific part of the parametrium when the pararectal and paravesical spaces are developed surgically. According to usual nerve-sparing radical hysterectomy (the Tokyo method), the CL is divided into two parts, the vascular part for dissection and the nerve part that contains the pelvic splanchnic nerve (PSN) as a major target for nerve sparing. In contrast, we hypothesized that the CL and another structure outside of the usual area for surgical dissection, that is, the lateral rectal ligament, are mutually continuous and that the PSN runs through the lateral ligament rather than the CL. In the present study, a combination of routine dissection, fresh cadaver dissection and in situ sectional anatomy revealed that: (i) the CL did not contain the PSN; (ii) a well-defined fascial structure existed in the bottom or dorsal margin of the CL area; and (iii) the pelvic plexus was separated from vascular components of the CL. The present results provide a new perspective for nerve-sparing radical hysterectomy with extensive lateral parametrial dissection of the CL.

Effect of cryoinjury on the contractile parameters of bladder strips: a model of impaired detrusor contractility.

In anesthetized Sprague-Dawley rats, the bladder was exposed and cryoinjury was induced by abruptly freezing the serosal side of the bladder wall with a chilled aluminum rod previously placed on dry ice (-40 degrees C). Five days later, the rats were euthanized, and strips were prepared from the area adjacent to the injury. Neurally and alpha,beta methylene-ATP (alpha,beta m-ATP; 50 microM)-evoked contractions were measured in bladder strips from cryoinjured or intact bladders prepared from sham-operated rats. Cryoinjured bladder strips produced significantly lower contractile forces than intact strips to electrical stimulation at higher (10-40 Hz) frequencies. The maximal rate of the neurally evoked contractions was slower in the cryoinjured bladders. The contractile response to alpha,beta m-ATP was smaller in the cryoinjured preparations indicating that the changes may have also occurred at the postjunctional site. In addition, atropine was more effective at inhibiting the neurally evoked contractions in the cryoinjured bladder strips suggesting that a cholinergic dominance occurs after cryoinjury. It is concluded that cryoinjury is a viable method of causing a defined, reproducible injury to the urinary bladder resulting in impaired function of both the cholinergic transmission and the smooth muscle. The bladder cryoinjury can be used as a model for studying impaired bladder compliance and detrusor contractility as well as treatments that may improve bladder function such as tissue engineering.