Biomedical subjects

J M Kerns

Publications and source records attributed to J M Kerns.

At least 19 recordsLinked to original sources

PubMed2007

Increased duration of simulated childbirth injuries results in increased time to recovery.

Stress urinary incontinence (SUI) development is strongly correlated with vaginal childbirth, particularly increased duration of the second stage of labor. However, the mechanisms of pelvic floor injury leading to SUI are largely unknown. The aim of this study was to determine the effects of increased duration of vaginal distension (VD) on voiding cystometry, leak point pressure testing, and histology. Sixty-nine virgin female rats underwent VD with an inflated balloon for either 1 or 4 h, while 33 age-matched rats were sham-VD controls. Conscious cystometry, leak point pressure testing, and histopathology were determined 4 days, 10 days, and 6 wk after VD. The increase in abdominal pressure to leakage (LPP) during leak point pressure testing was significantly decreased in both distension groups 4 days after distension, indicative of short-term decreased urethral resistance. Ten days after VD, LPP was significantly decreased in the 4-h but not the 1-h distension group, indicating that a longer recovery time is needed after longer distension duration. Six weeks after VD, LPP was not significantly different from sham-VD values, indicating a return toward normal urethral resistance. In contrast, 6 wk after VD of either duration, the distended rats had not undergone the same increase in voided volume as the sham-VD group, suggesting that some effects of VD do not resolve within 6 wk. Both VD groups demonstrated histopathological evidence of acute injuries and tissue remodeling. In conclusion, this experiment suggests pressure-induced hypoxia as a possible mechanism of injury in vaginal delivery.

Animals↗

PubMed2004

Early structural effects of oestrogen on pudendal nerve regeneration in the rat.

OBJECTIVE: To determine the early effects of oestrogen on the ultrastructure of the pudendal nerve and distal nerve fascicles near the external urethra sphincter (EUS) after a pudendal nerve crush injury. The pudendal nerve is one of the pelvic floor tissues injured during vaginal delivery, possibly contributing to the development of stress urinary incontinence (SUI) in women, the symptoms of which often do not appear until menopause, implicating hormonal factors. MATERIALS AND METHODS: Twenty-seven virgin female Sprague-Dawley rats were anaesthetized and underwent ovariectomy. Three days later, they had one of four procedures: bilateral pudendal nerve crush plus implant of a subcutaneous oestrogen-containing capsule (NC+E); nerve crush plus implant of a sham saline-containing capsule (NC+S); no nerve crush with an oestrogen capsule; or no nerve crush with a sham capsule. After 2 weeks the pudendal nerves and urethral tissues were prepared for light and electron microscopy. The number of axons, myelin figures and endoneurial nuclei in the pudendal nerve segment distal to the lesion were counted. Nerve fascicles near the EUS were also counted and categorized as normal or showing signs of degeneration and/or regeneration. The location of each nerve fascicle was specified as either ventral or dorsal. RESULTS: As there were no significant differences between the two control groups they were combined to form a single control group. In the distal pudendal nerve there were significantly fewer myelinated axons and large myelinated axons in the NC+E and NC+S groups than in the control group. There were three times as many large unmyelinated axons in the NC+E group than in either the NC+S or control groups (P < 0.05). There were only half as many nerve fascicles near the ventral side of the EUS in the NC+S group than in both the control and NC+E groups (P < 0.05). CONCLUSION: Oestrogen appears to affect large unmyelinated axons in both the injured pudendal nerve and at the denervated EUS target. After pudendal nerve crush, nerve fascicles with evidence of degeneration or regeneration near the EUS appear to be spared with oestrogen treatment, particularly in the ventral region. These observations may reflect the early stages of a neuroregenerative effect of oestrogen. Additional studies are needed to confirm these results at later periods and with functional methods.

Animals↗

PubMed2003

Effects of IGF-I gene therapy on the injured rat pudendal nerve.

Injured nerves and their motor units may undergo enhanced recovery when exposed to recombinant human insulin-like growth factor-I (rhIGF-I). The external anal sphincter muscle in the female rat was denervated to model incontinence. The treatment-group muscle was injected with rhIGF-1 plasmid, whereas in the control group the plasmid lacked the cDNA insert and the normal group received neither surgery nor treatment. Electromyography data at 56 days post surgery indicated more reinnervation without fibrillation potentials in the treatment group (2 of 6) than in the control group (0 of 6). The histology of the regenerated axons in the pudendal nerve distal to the crush site also suggested an improved recovery in the treatment group. The number of motor neurons retrogradely labeled with horseradish peroxidase was decreased by 50% following pudendal nerve crush in both experimental groups compared to the normal group. We conclude from these preliminary results that rhIGF-I gene therapy may improve the distal recovery of structure and function.

Anal Canal↗

PubMed2001

Functional and structural effects of GM-1 ganglioside treatment on peripheral nerve grafting in the rat.

Peripheral nerve regeneration after traumatic injury and standard repair with a nerve autograft is usually incomplete. This study tested the influence of graft vascularity and pharmacological intervention with GM-1 ganglioside on nerve regeneration in a rat sciatic nerve model. Controls included an unoperated contralateral side and sham-operated groups either with or without the GM-1. During the 5 months of recovery, locomotion was tested by the sciatic function index (SFI). At killing, anesthetized animals were prepared for nerve conduction velocity (NCV) studies, followed by the wet weight of the gastrocnemius muscle (expression of atrophy), toe-chewing (expression of lesion severity and sensory loss), and histological examination of the nerve segments. The SFI showed a slight but significant recovery for both the vascular and avascular groups (34% at 20 weeks), but when GM-1 ganglioside treatment was included, the SFI was poor throughout (20-33%). The average NCV of the graft groups without GM-1 was 46% to 57% of the normal nerve (52.7 m/s), whereas for the groups treated with GM-1, it was 63% to 64% of normal; treatment of the non-vascular graft group significantly improved recovery. A uniformly poor recovery from muscle atrophy was seen for all nerve graft groups (62-67%) compared with normal controls. The mean number of toes per foot chewed was 1.9 and 2.4 in graft groups without GM-1 treatment and 0.9 and 1.3 in graft groups treated with GM-1. This treatment significantly reduced both the extent and the number of animals exhibiting autotomy. The qualitative microscopic appearance of the distal nerve segment in all surgical groups was similar. We conclude that the systemic addition of GM-1 ganglioside enhances only some aspects of regeneration in grafted nerves, possibly with a preferential effect on sensory nerve regeneration and functional recovery.

Animals↗

PubMed2000

Effects of pudendal nerve injury in the female rat.

To test a neurogenic hypothesis for external urethral sphincter (EUS) dysfunction associated with urinary incontinence, the proximal pudendal nerve was crushed in anesthetized retired breeder female rats (n = 5) and compared with a sham lesion group (n = 4). Outcome measures included concentric needle electromyograms (EMGs) from the target EUS, voiding patterns during a 2-hour dark period, and micturition data over a 24-hour period. Fast Blue (FB) was introduced to the crush site at the time of injury and Diamidino Yellow (DY) to the EUS at the time the rats were killed (3 months post-operative), when histological analysis of the nerve and urethra was also performed. EMG records indicated the EUS motor units undergo typical denervation changes followed by regeneration and recovery. Voiding patterns from the crush group show a significant increase of small urine marks in the front third of the cage. At 1-2 weeks post-op, the frequency of voids was significantly increased in the crush group compared to pre-op and late post-op time periods. The mean volume voided in the light phase at the early post-op time was significantly increased in the sham group. Light and electron microscopic patterns seen in nerve and muscle suggest the regenerating motor units maintain a structural integrity. Motoneurons in the lower lumbar cord were labeled with either DY (14. 5 +/- 6.8), FB (31.7 +/- 23.7), or both (35.0 +/- 17.5) tracers, indicating approximately 54% of the crushed pudendal neurons regenerated to the EUS. In conclusion, several measures suggest this reversible crush lesion induces mild urinary incontinence. This animal model is promising for further development of hypotheses regarding neural injury, the pathogenesis of incontinence, and strategies aimed at prevention and treatment. Neurourol. Urodynam. 19:53-69, 2000.

Animals↗

PubMed1996

Do direct current electric fields enhance micturition in the spinal cat?

Changes in micturition behavior and motoneuron ultrastructure were studied in spinal cats to determine the effects of direct current (DC) electric field treatment. Adult cats received a complete injury at T8. A treatment group with an implanted 15 microA DC source and electrodes positioned near the lesion site was compared with non-treatment groups that were either operated or unoperated. Both bladder emptying with Crede and the withdrawal reflex were improved in the treatment group compared with the non-treatment group. Urodynamic procedures showed that high urethral resistance and pelvic floor activity following spinal injury was partially reduced in the stimulated cat, indicating inhibition of the urethral sphincter. The ultrastructural analysis of Onuf's nucleus suggested a similar synaptic input in all three groups. In conclusion, possible activation of inhibitory processes and/or neural plasticity best explain the early improvement of bladder function seen following electrical stimulation.

Animals↗

PubMed1995

Predegeneration enhances regeneration into acellular nerve grafts.

In the present study, we determined the regeneration rate and the initial delay in rat sciatic nerve grafts first made hypercellular by predegeneration then acellular by freeze-thawing. 7-day predegenerated nerve pieces from the distal nerve stump on the right side were made acellular by repeated freeze-thawing and inserted as grafts into a 10-mm long freshly created defect on the left contralateral side. Freshly made (no predegeneration period) acellular nerve grafts were used as controls. Both types of grafts supported outgrowth of regenerating axons as demonstrated by the sensory pinch test. However, the predegenerated acellular nerve grafts had a significantly shorter initial delay period (2.7 days) as compared with freshly made acellular nerve grafts (9.5 days). The initial delay period for predegenerated acellular nerve grafts was similar to that for fresh cellular nerve grafts but significantly longer than that for predegenerated cellular nerve grafts [24]. The rate of regeneration appeared independent of the type of grafts used. We suggest that modifications of the basal lamina and/or factors produced during the predegeneration period by non-neuronal cells survive the freeze-thawing cycle and account for the decrease in the initial delay period.

Animals↗

PubMed1995

Long-term local corticosteroid application does not influence nerve transmission or structure.

The long-term effects of a locally applied depot form of a corticosteroid on the electrical properties and structure of nerves were investigated in an animal experimental model. The conduction in electrically stimulated A-fibres of the plantar nerve was monitored by a bipolar volley recording of the sciatic nerve whereas the conduction in C-fibres of the plantar nerve was measured through a C-fibre evoked segmental flexion reflex in the anaesthetized rat. Droplets of either methylprednisolone acetate or vehicle were placed under direct observation on the plantar nerve. Saline was used as a control on the contralateral side. One to two weeks after the application both the A-fibre volley of the sciatic nerve and the C-fibre evoked reflex discharge of flexor motoneurons were recorded. No difference was found between the nerves treated with corticosteroid, constituent vehicle or saline. Light and electron microscopic analysis of the nerves showed no changes in the nerve fibres or in the intraneural connective tissue in either the corticosteroid treated or the control nerves. It is concluded that locally applied corticosteroids in limited amounts have no long-term effects on the electrical and structural properties of peripheral nerves.

Administration, Topical↗

PubMed1994

Pre-degenerated nerve grafts enhance regeneration by shortening the initial delay period.

In the present study we tested how nerve grafts with different pre-degeneration periods (1-28 days) influenced the early regenerative response in the rat sciatic nerve. The sciatic nerve on the right side was crushed and after 1-28 days of pre-degeneration, a 10 mm segment was used as an autologous nerve graft and transposed to a freshly made 10 mm long nerve defect on the left side. The regeneration distance was measured by the sensory pinch test 2-10 days after nerve repair. A newly developed mathematical model was used to calculate regeneration rates and initial delay periods from the measured regeneration distances. Pre-degenerated nerve grafts improved nerve regeneration by decreasing the initial delay period as compared to fresh nerve grafts without affecting the regeneration rate. Only one day of pre-degeneration was sufficient to reduce the initial delay period from 3.6 days to 1.7 days. The maximal effect on the initial delay period was achieved after 3 days of pre-degeneration. The initial delay period at later pre-degeneration intervals (7-14 days) was about 1 day. The effect persisted for at least 28 days of pre-degeneration. The regeneration rate was 1.5 mm/day for fresh nerve grafts and between 1.8-2.1 mm/day for pre-degenerated grafts. The results suggest that the effects of pre-degeneration are not only due to the increased cell proliferation in the graft, but that also trophic and/or inflammatory mechanisms may be of importance. Grafts pre-degenerated by crush may have clinical implications since they are easy to perform if an elective nerve grafting procedure is planned.

Animals↗

PubMed1994

Effects of predegeneration on nerve regeneration through silicone Y-chambers.

The effects of nerve predegeneration on the preferential growth of regenerating axons were studied using a silicone Y-chamber model. This system provided a choice for axons to grow towards two distal nerve options, either a 7-day predegenerated nerve segment (PNS) or a fresh nerve segment (FNS). The rat peroneal or tibial nerve was inserted into the proximal intlet and the PNS and FNS of the corresponding nerve were inserted into the distal outlets. At 28 days postoperative, the size of the distal regenerate was significantly greater (26%) towards the PNS for the tibial nerve group. The density and number of regenerated myelinated axons in the distal nerve segment was greater on the PNS for both the tibial (97 and 88%, respectively) and peroneal (221 and 221%, respectively) nerve groups. In contrast, the elevated density and number of nonvascular nuclei was relatively constant for both PNS and FNS. Immunocytochemical and ultrastructural evidence support the hypothesis that the early activation of Schwann cells is primarily responsible for the enhanced regeneration and maturation observed in PNS. It is suggested that PNS might improve the outcome after clinical repair of injured peripheral nerves.

Animals↗

PubMed1994

Laser effects on myelinated and nonmyelinated fibers in the rat peroneal nerve: a quantitative ultrastructural analysis.

We have recently shown that Nd:YAG laser irradiation of rat peripheral nerve differentially impairs action potential transmission in small, slowly conducting sensory fibers compared to fast conducting afferents. In addition, the number of small sensory neurons of the A-delta- and C-fiber group labeled with HRP is significantly reduced after laser irradiation, while the number of labeled large sensory neurons and motoneurons was not affected. To further evaluate this laser-induced injury, we examined three distinct regions of the laser-irradiated rat peroneal nerve using ultrastructural morphometric methods. These regions were the site of laser irradiation and zones 10 mm proximal and 5 mm distal to the injury. The contralateral nerve was sham treated. Our results indicate that for the small nonmyelinated fibers, there was a significant increase in both mean fiber size and the number of microtubules per fiber, but a decrease in the number of neurofilaments. In contrast, the number of myelinated and nonmyelinated fibers is not significantly altered at 7 days following laser irradiation, and the mean diameter and frequency distribution of myelinated nerve fibers was unchanged. This study demonstrates that selective functional alterations in laser-irradiated nerves (nerve conduction velocity, HRP transport properties) are accompanied by ultrastructural changes of axonal organelles in nonmyelinated fibers. Nd:YAG laser light might ultimately prove to be a powerful tool to selectively alter functional properties in small, slowly conducting afferent fibers, without causing degeneration at the ultrastructural level at the site of irradiation. We hypothesize further that the laser-induced functional alterations might be related to differential thermally mediated changes.

Animals↗

PubMed1994

Can sensory and motor collateral sprouting be induced from intact peripheral nerve by end-to-side anastomosis?

The possibility that collateral sprouting could occur from intact axons in an undamaged sciatic nerve was studied in the rat by suturing either a 7-day predegenerated or a fresh nerve segment in an end-to-side fashion to the sciatic nerve proper. Following a 14- or 35-day recovery period, the pinch reflex test was performed on the transplanted segment to demonstrate the presence of sensory axons. The majority of cases, using a predegenerated nerve segment but not a fresh segment, responded positively. Neurofilament staining and histological examination confirmed the presence of axons in the attached nerve segment. In another series of experiments, the proximal peroneal fascicle was ligated and cut. Following a 7-day predegeneration period the distal stump was sutured end-to-side to the ipsilateral tibial fascicle. After 90 days, stimulation of the tibial nerve proximal to the attached site induced substantial contraction in both the native gastrocnemius muscle and the foreign tibialis anterior muscle. These findings suggest that collateral sprouting may occur from intact axons, perhaps induced by factors emanating from the attached nerve segment, and subsequently make functional peripheral connections.

Anastomosis, Surgical↗

PubMed1993

The influence of predegeneration on regeneration through peripheral nerve grafts in the rat.

Nerve regeneration through predegenerated (PNG) or fresh (FNG) autografts in either fresh or delayed recipient nerve beds were studied in the rat sciatic nerve. Grafts 10 mm in length were excised either immediately or following a 7-day period of predegeneration. They were sutured into gaps on the contralateral side which were either freshly made or had been made 7 days previously. The early recovery (10 days at 2-day intervals) was evaluated by the sensory pinch test to measure the rate of regeneration and the delay period. The PNG group had an improvement in axonal regeneration as evidenced by a reduced delay period, a reduced number of regeneration failures, and less variability in regeneration distances compared to the FNG group. Conditioning the host site blocked some of the delay reduction in the PNG group, but had no effect on regeneration rate or delay in the FNG group. The presence of axons in the graft was confirmed by immunocytochemistry for neurofilament protein and by electron microscopy. The results suggest that proliferated cells, primarily Schwann cells, promote regeneration through the suture line and graft into the distal segment.

Animals↗

PubMed1993

A mathematical model for regeneration rate and initial delay following surgical repair of peripheral nerves.

A mathematical model is presented by which the regeneration rate and initial delay for peripheral nerve regeneration can be calculated from sensory pinch test data following surgical repair of peripheral nerves. The model is based on the assumption that experimental variations in regeneration distances between animals is due to the initial delay period--the time period before the regenerating fibers cross the suture line whereas the rate of regeneration is constant. This model which accounts for all observed data including 'regenerating failures' showed that nerve fibers in the rat sciatic nerve repaired with a fresh nerve graft regenerated at a rate of 1.5 mm/day after an initial delay of 3.6 days.

Animals↗

PubMed1992

Electrical field effects on crushed nerve regeneration.

The delivery of an electrical field to a transected nerve has been shown to enhance the regeneration. This study examined the effects of such fields on the regeneration of crushed rat sciatic nerve during the first postoperative month. The treated (T) nerve group received a battery implant delivering 10 microA with the cathode at the distal stump. The recovery was compared to an untreated (UT) group and unoperated controls (C). The loss of locomotion behavior and partial recovery (SFI) was identical for the T and UT groups. The index of motor recovery (twitch tension) was also similar (T/C = 48%, UT/C = 53%), but a "window" of enhancement occurred 2-4 days earlier in the T group. Qualitative histology at 28 days suggested a more healthy and normal-appearing nerve in the T group. Morphometric analysis indicated that the nerve area, fiber density, and fiber number in the T group were more similar to those in the control group than to those in the UT group. There were no group differences in the number of HRP-labeled motoneurons, but the enlarged endoneurial space was significantly reduced in the T group compared to the UT group. In conclusion, electrical fields appeared to have a small effect on some aspects of nerve regeneration following crush injury.

Analysis of Variance↗

PubMed1992

Synaptic plasticity in the rat striatum following chronic haloperidol treatment.

Administration of the dopamine (DA) antagonist haloperidol leads to the development of behavioral hypersensitivity as well as enhanced neuronal growth when striatal extracts from these animals are incubated with mesencephalic cultures. For determining if alterations in neuronal growth also occur in vivo, the ultrastructure of the neuropil in the dorsolateral quadrant of the striatum from rats treated (24 days) with haloperidol (1.25 mg/kg) was examined by electron microscopy. Haloperidol-treated rats developed statistically significant behavioral hypersensitivity relative to vehicle-treated controls (p < 0.01). Evaluation of the neuropil revealed that haloperidol treatment enhanced, relative to vehicle-treated controls, the overall number of synaptic boutons by 9% (p < 0.01). The number of perforated synaptic profiles as well as the number of double synapses was increased by 20 and 50%, respectively, although this increase was not statistically significant. The number of myelinated axons remained unchanged, while the number of dendritic spines was increased by 21% (p < 0.05). These data suggest that chronic haloperidol treatment enhanced the growth and possible sprouting of presynaptic neurons and also induced postsynaptic plastic changes. These ultrastructural changes may contribute in part to hypersensitivity behaviors.

Animals↗

PubMed1991

Electrical stimulation of nerve regeneration in the rat: the early effects evaluated by a vibrating probe and electron microscopy.

This study examines the effect of applied d.c. electric fields on nerve regeneration following injury to the rat sciatic nerve using the circularly vibrating probe and electron microscopy. The transected and treated nerve which received a d.c. electrical stimulator (0.6 mu A) was compared with untreated transected and crushed nerves. At one week postoperative, the probe was used to measure in vivo the current density along the nerve length. All nerves studied had a proximal peak at the lesion site and a second peak at varying distal locations: crushed/untreated (13.3 mm), transected/untreated (9.7 mm) and transected/treated (16.3 mm). A significant difference (69%) between the distal peak distances in the two transection groups suggests that the electrical treatment enhanced the progress of nerve regeneration. There were no significant differences between the mean peak amplitudes (1.6-2.2 mu A/cm2). Applied verapamil reduced the peaks, suggesting they are associated in part with a calcium-dependent current. Electron microscopy at selected nerve regions indicated that the peaks correspond to regenerating axonal growth cones. The results suggest the potential clinical application of d.c. electric fields in the treatment of nerve injuries.

Animals↗

PubMed1989

Chronic access to endoneurial space using an arterial autograft.

A technique for direct chronic infusion of compounds onto peripheral axons has been investigated in the rat sciatic nerve. A 2 cm segment of the femoral artery was removed and one end inserted into the endoneurial space of the contralateral peroneal nerve fascicle of the same animal. The other end of the artery was connected to a catheter system to allow infusion into the endoneurium, thus bypassing the barrier that the perineurium presents to hydrophilic compounds. The patency of this arterial access system was evaluated by the ability of 20 microliters of 2% lidocaine to inhibit the toe-spreading reflex. The results of the study were that the infusion system remained operational for 3-7 days after transplantation. There were histologic changes in the nerve but there were no functional deficits due to the surgery. Although a long-term endoneurial infusion was not achieved, the limited access time to the axons might be long enough for applications such as the delivery of nerve growth factors to injured nerve.

Animals↗