Now showing 1 - 7 of 7
  • Publication
    Acute lumbosacral nerve stimulation does not affect anorectal motor function in a rodent model
    Background: Sacral nerve stimulation has become a first line treatment for fecal incontinence, however, its effect on the motor function of the anorectum is uncertain. The aim of this study was to apply acute lumbosacral nerve stimulation in an animal model and to determine its effect on the external and internal anal sphincter forces, the rectoanal inhibitory and excitatory reflexes, and the slow wave frequency of the internal anal sphincter. Methods: Lumbosacral nerve stimulation was applied to 16 nulliparous female rats. A novel in vivo preparation was designed to allow simultaneous monitoring of external and internal anal sphincter forces. The effect of rectal distension on the two anal sphincters was also studied. Key Results: Lumbosacral nerve stimulation delivered at either S or L in rodents did not affect sphincter forces, rectoanal reflexes or slow wave frequency of anal canal smooth muscle. Conclusions & Inferences: The absence of effect on the motor pathways of continence suggests that the mechanism of action is predominantly on sensory feedback mechanisms from the anorectum, thereby increasing cortical awareness of the pelvic floor.
      62Scopus© Citations 4
  • Publication
    Estimation of dispersive properties of encapsulation tissue surrounding deep brain stimulation electrodes in the rat
    The aim of this study was to estimate the electrical properties of the encapsulation tissue surrounding chronically implanted electrodes for deep brain stimulation in the rat. The impedance spectrum of a concentric bipolar microelectrode implanted in the rat brain was measured immediately following surgery and after 8 weeks of implantation. The experimental impedance data were used in combination with a finite element model of the rat brain using a parametric sweep method to estimate the electrical properties of the tissue surrounding the electrode in acute and chronic conditions. In the acute case, the conductivity and relative permittivity of the peri-electrode space were frequency independent with an estimated conductivity of 0.38 S/m and relative permittivity of 123. The electrical properties of the encapsulation tissue in the chronic condition were fitted to a dispersive Cole-Cole model. The estimated conductivity and relative permittivity in the chronic condition at 1 kHz were 0.028 S/m and 2×10 5 , respectively. The estimated tissue properties can be used in combination with computational modeling as a basis for optimization of chronically implanted electrodes to increase the efficacy of long-term neural recording and stimulation.
      358Scopus© Citations 1
  • Publication
    Reversal of sensory deficit through sacral neuromodulation in an animal model of fecal incontinence
    Background: Sacral neuromodulation (SNM) is a treatment option for intractable fecal incontinence. The mechanism of action is unclear, however, increasing evidence for afferent somatosensory effects exists. This study's aim was to elucidate effects of acute SNM on the cerebral cortex in a rodent model of pudendal nerve injury. Methods: The effects of 14 Hz and 2 Hz SNM on sensory cortical activation were studied. In 32 anesthetized rats, anal canal evoked potentials (EPs) were recorded over the primary somatosensory cortex. Pudendal nerve injury was produced by 1-hour inflation of two intra-pelvic balloons. Four groups were studied: balloon injury, balloon injury plus either 14 Hz or 2 Hz SNM, sham operation. Immunohistochemistry for the neural plasticity marker polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells (numerical density and location) in the somatosensory cortex was performed. Key Results: Anal EP amplitudes diminished during balloon inflation; 14 Hz SNM restored diminished anal EPs to initial levels and 2 Hz SNM to above initial levels. Evoked potential latencies were prolonged during balloon inflation. The numerical density of PSA-NCAM positive cells increased in the SNM groups, but not in sham or balloon injury without SNM. Stimulated cortices showed clusters of PSA-NCAM positive cells in layers II, IV, and V. Post SNM changes were similar in both SNM groups. Conclusions & Inferences: Sacral neuromodulation augments anal representation in the sensory cortex and restores afferent pathways following injury. PSA-NCAM positive cell density is increased in stimulated cortices and positive cells are clustered in layers II, IV, and V.
      87Scopus© Citations 15
  • Publication
    The Relationship Between Cortical Activation in Response to Anorectal Stimuli and Continence Behavior in Freely Behaving Rats Before and After Application of Sacral Nerve Stimulation
    (Diseases of the Colon and Rectum, 2022-02-01) ; ;
    Background: Changes in anorectal sensation have been reported in patients with fecal incontinence and there is limited evidence that sacral nerve stimulation can restore normal sensation. Objective: The aims of the present study were to investigate changes in transmission of sensory anorectal stimuli in a rodent model of FI and to study the effects of SNS on defecation behaviour. Design & Interventions: An established model of fecal incontinence using pudendal nerve stretch and compression was used in 16 adult female Wistar rats and followed for 3 weeks: six rats received sacral nerve stimulation for 1 week using an implantable neurostimulator and ten rats had non-functioning ‘dummy’ devices inserted. Five additional rats were sham operated. Anorectal cortical evoked potentials were used as a surrogate marker for anorectal sensory function. Main Outcome Measures: Faecal incontinence index, evoked potential amplitude and latency. Results: Fifty percent of rats showed behavioral signs of FI measured by the Fecal Incontinence Index(>0.20), calculated using the pellet distribution outside the cage’s latrine area. Anorectal evoked potential amplitude was reduced in rats with an fecal incontinence index >0.20(p=0.019). The amplitude of forepaw evoked potentials recorded as a control was not different between groups. Sacral nerve stimulation using the fully implantable device and custom rodent lead was safe and stable during this prospective study. Incontinent rats(N=3) that received sacral nerve stimulation showed an improvement of fecal incontinence indexand an increase of evoked potential amplitude to anorectal stimulation compared to the dummy implant controls (N=5). Limitations: The main limitation is the small number of animals that received sacral nerve stimulation. Conclusions: Chronic sacral nerve stimulation is feasible in rats when miniature telemetric devices are used. Behavioral signs of fecal incontinence were positively correlated with latency of anorectal evoked potentials.
  • Publication
    The Active Electrode in the Living Brain: The Response of the Brain Parenchyma to Chronically Implanted Deep Brain Stimulation Electrodes
    (Oxford University Press, 2019-02) ;
    BACKGROUND: Deep brain stimulation is an established symptomatic surgical therapy for Parkinson disease, essential tremor, and a number of other movement and neuropsychiatric disorders. The well-established foreign body response around implanted electrodes is marked by gliosis, neuroinflammation, and neurodegeneration. However, how this response changes with the application of chronic stimulation is less well-understood. OBJECTIVE: To integrate the most recent evidence from basic science, patient, and postmortem studies on the effect of such an "active"electrode on the parenchyma of the living brain. METHODS: A thorough and in-part systematic literature review identified 49 papers. RESULTS: Increased electrode-tissue impedance is consistently observed in the weeks following electrode implantation, stabilizing at approximately 3 to 6 mo. Lower impedance values are observed around stimulated implanted electrodes when compared with unstimulated electrodes. A temporary reduction in impedance has also been observed in response to stimulation in nonhuman primates. Postmortem studies from patients confirm the presence of a fibrous sheath, astrocytosis, neuronal loss, and neuroinflammation in the immediate vicinity of the electrode. When comparing stimulated and unstimulated electrodes directly, there is some evidence across animal and patient studies of altered neurodegeneration and neuroinflammation around stimulated electrodes. CONCLUSION: Establishing how stimulation influences the electrical and histological properties of the surrounding tissue is critical in understanding how these factors contribute to DBS efficacy, and in controlling symptoms and side effects. Understanding these complex issues will aid in the development of future neuromodulation systems that are optimized for the tissue environment and required stimulation protocols.
      164Scopus© Citations 6
  • Publication
    Feasibility of pair-housing of rats after cranial implant surgery
    Rat models employing cranial implants are increasingly employed to facilitate neural stimulation and recording in freely moving animals. Due to possible damage to wound, implant or attached devices, rats with cranial implants are traditionally housed singly, and little information is available on group- or pair-housing. Here we describe a protocol for pair-housing rats following cranial implant surgery and describe our experience with pair-housing during post-surgical recovery and up to 16 weeks following surgery.Thirty-six adult Wistar rats of both sexes were implanted with deep brain stimulation electrodes. Ten rats were equipped with an additional wireless headstage. Rats were housed in stable pairs before surgery and re-introduced 0-18 h post-surgery. Rat grimace scores did not indicate pain after conclusion of the analgesia protocol, physiological parameters were in the normal range three days post-surgery and weight loss did not exceed 10%. Rats with a cement cap only were pair-housed continuously without damage to the headcap. Rats carrying an additional fragile headstage had to be separated during lights-off periods to prevent headstage damage but could be pair-housed during lights-on periods. Pair-housing is a feasible and effective method to facilitate the rats' need for social companionship following cranial implant surgery.
  • Publication
    Mechanically evoked cortical potentials: A physiological approach to assessment of anorectal sensory pathways
    Background: Normal defaecation involves activation of anorectal mechanoreceptors responsive to pressure and stretch. The aim of this study was to develop selective anal and rectal mucosal light-touch stimulation suitable for measurement of cortical evoked potentials (EPs) in order to explore the sensory arm of these pathways. New method: A novel device was manufactured to deliver selective rectal and/or anal light-touch stimulation using a shielded inter-dental brush mounted on a rotating stepper motor (1 Hz, 1 ms, 15° rotation). Resultant somatosensory EPs recorded with a 32-channel cortical multi-electrode array were compared to those elicited by electrical anorectal stimulation (2 mm anal plug electrode [1 Hz, 1 ms, 10 V]). Results: Eighteen anaesthetized female Wistar rats (body mass 180-250 g) were studied. Electrical and mechanical stimulation provoked similar maximal response amplitudes (electrical anorectal 39.0 μV[SEM 5.5], mechanical anal 42.2 μV[8.1], mechanical rectal 45.8 μV[9.0]). Response latency was longer following mechanical stimulation (electrical anorectal 8.8 ms[0.5], mechanical anal 16.4 ms[1.1], mechanical rectal 18.3 ms[2.5]). The extent of activated sensory cortex was smaller for mechanical stimulation. Sensory inferior rectal nerve activity was greater during anal compared to rectal mechanical in a subgroup of 4 rats. Evoked potentials were reproducible over 40 min in a subgroup of 9 rats. Comparison with existing methods: Cortical EPs are typically recorded in response to non-physiological electrical stimuli. The use of a mechanical stimulus may provide a more localized physiological method of assessment. Conclusions: To the authors' knowledge these are the first selective brush-elicited anal and rectal EPs recorded in animals and provide a physiological approach to testing of anorectal afferent pathways.
      67Scopus© Citations 6