scholarly journals Dual forms of aging-related NADPH diaphorase neurodegeneration in the sacral spinal cord of aged non-human primates

2019 ◽  
Author(s):  
Yinhua Li ◽  
Zichun Wei ◽  
Yunge Jia ◽  
Wei Hou ◽  
Yu Wang ◽  
...  

AbstractWe discovered two different anomalous NADPH diaphorase (NADPH-d) positive alterations, which were expressed as aging-related NADPH-d positive spheroidal bodies and megaloneurites specially distributed in the superficial dorsal horn, dorsal gray commissure (DGC), lateral collateral pathway (LCP) and sacral parasympathetic nucleus (SPN) in the aged monkeys’ sacral spinal cord, compared with the cervical, thoracic and lumbar segments. In the gracile nucleus of aged monkeys, only aging-related spheroidal bodies were observed and no megaloneurites occurred. The dense, abnormal NADPH-d positive megaloneurites, extremely different from regular NADPH-d positive fibers, were prominent in the sacral segments and occurred in extending from Lissauer’s tract (LT) through lamina I along the lateral boundary of the dorsal horn to the region of the SPN. Meanwhile, large diameter punctate NADPH-d activity occurred and scattered in the lateral white matter of the LCP and dorsal root entry zone (DREZ) at the same level of NADPH-d abnormality in the gray matters. Those dot-like NADPH-d alterations were examined by horizontal sectioning and indicated ascending or descending oriental fibers. These NADPH-d megaloneurites had the same composition as the punctate NADPH-d alterations and were co-localized with the VIP immunoreaction, while the ANBs did not coexist with the VIP immunoreaction. Both ANBs and megaloneurites provide consistent evidence that the anomalous neuritic alterations in the aged sacral spinal cord are referred to as a specialized aging marker in the pelvic visceral organs in non-human primates.

2018 ◽  
Author(s):  
Yinhua Li ◽  
Yunge Jia ◽  
Wei Hou ◽  
Zichun Wei ◽  
Xiaoxin Wen ◽  
...  

AbstractThe aging-related changes of NADPH-diaphorase (NADPH-d) in the spinal cord were studied in aged dogs. At all levels of the spinal cord examined, NADPH-d activities were present in neurons and fibers in the superficial dorsal horn, dorsal commissure and in neurons around the central canal. In addition, the sympathetic autonomic nucleus in the thoracic and rostral lumbar segments exhibited prominent NADPH-d cellular staining whereas the sacral parasympathetic nucleus (SPN) in the sacral segments was not well stained. Interestingly, we found abundant NADPH-d positive enlarged-diameter fibers termed megaloneurite, which characteristically occurred in the aged sacral segments, distributed in the dorsal gray commissure (DGC), lateral collateral pathway (LCP) the lateral fasciculi and the central canal compared with the cervical, thoracic and lumbar segments. The dense, abnormal NADPH-d megaloneurites occurred in extending from dorsal entry zone through lamina I along with the lateral boundary of the dorsal horn to the region of the SPN. These fibers were prominent in the S1-S3 segments but not in adjacent segments L5-L7 and Cx1 or in thoracolumbar segments and cervical segments. Double staining with GFAP, NeuN, CGRP, MAP2 and Iba1, NADPH-d megaloneurite colocalized with vasoactive intestinal peptide. Presumably, the megaloneurites may represent, in part, visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.


2021 ◽  
Author(s):  
Manon Duraffourg ◽  
Andrei Brinzeu ◽  
Marc Sindou

Abstract More than three-quarters of victims of brachial plexus injury suffer from refractory neuropathic pain.1-6 Main putative mechanism is paroxysmal hyperactivity in the dorsal horn neurons at the dorsal root entry zone (DREZ) as demonstrated by microelectrode recordings in animal models7 and patients.8 Pain relief can be achieved by lesioning the responsible neurons in the spinal cord segments with avulsed rootlets.9,10  This video illustrates the technique for microsurgical DREZotomy.11,12 A C3-C7 hemilaminectomy is performed to access the C4-Th1 medullary segments. After opening the dura and arachnoid, and freeing the cord from arachnoid adhesions, the dorsolateral sulcus is identified. Identification can be difficult when the spinal cord is distorted and/or has a loss of substance. The dorsolateral sulcus is then opened with a microknife, so that microcoagulations are performed: 4 mm deep, at 35° angle in the axis of the dorsal horn, every millimeter in a dotted fashion along the avulsed segments. Care should be taken not to damage the corticospinal tract, laterally, and the dorsal column, medially.  The patient consents to the procedure. In the presented case, surgery led to complete disappearance of the paroxysmal pain and reduced the background of burning pain to a bearable level without the need of opioid medication. There was no motor deficit or ataxia in the ipsilateral lower limb postoperatively. According to Kaplan-Meier analysis at 10 yr follow-up, in our overall series, microsurgical DREZotomy achieved total pain relief without any medication in 60% of patients, and in 85% without the need for opioids.10,13-15  Microelectrode recording at 1:26 reproduced from Guenot et al7 with permission from JNSPG.


Neuroscience ◽  
1995 ◽  
Vol 68 (1) ◽  
pp. 167-179 ◽  
Author(s):  
L. Liu ◽  
E. To¨rnqvist ◽  
P. Mattsson ◽  
N.P. Eriksson ◽  
J.K.E. Persson ◽  
...  

2000 ◽  
Vol 278 (4) ◽  
pp. R1027-R1039 ◽  
Author(s):  
Margaret A. Vizzard

These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after cyclophosphamide (CYP)-induced bladder inflammation. In urethan-anesthetized Wistar rats with cystitis, intravesical saline distension significantly ( P ≤ 0.0005) increased the number of Fos-immunoreactive (IR) cells observed in the rostral lumbar (L1, 35 cells/section; L2, 27 cells/section) and caudal lumbosacral (L6, 120 cells/section; S1, 96 cells/section) spinal cord compared with control animals, but Fos protein expression in the L5 segment was not altered. The topographical distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. The majority of Fos-IR cells were distributed in the dorsal commissure (45%), with smaller percentages in the sacral parasympathetic nucleus (25%), medial dorsal horn (20%), and lateral dorsal horn (10%). These results demonstrate that urinary bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after cystitis. This altered distribution pattern resembles that following noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after cystitis. These data suggest that chronic cystitis can reveal a nociceptive Fos expression pattern in the spinal cord in response to a non-noxious bladder stimulus that is partially mediated by capasaicin-sensitive bladder afferents.


2012 ◽  
Vol 303 (3) ◽  
pp. F350-F356 ◽  
Author(s):  
Wenbin Yang ◽  
Charles N. Rudick ◽  
Eneda Hoxha ◽  
Stephen A. Allsop ◽  
Jordan D. Dimitrakoff ◽  
...  

Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. Interstitial cystitis is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area. In this study, we used a murine neurogenic cystitis model to identify genes participating in the development of pelvic pain. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic pain. The sacral spinal cord was harvested on postinfection days (PID) 2 and 4, and gene expression was analyzed by microarrays and confirmed by quantitative RT-PCR. On PID 2, the overall expression profile was similar to that of uninfected sacral spinal cord; by PID 4, there were substantial differences in expression of multiple functional classes of genes, especially inflammation. Analysis of pain-signaling pathways at the dorsal horn suggested that Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain. Consistent with this, CaMKIIδ expression exhibited a mast cell-dependent increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII immunoreactivity in the dorsal horn was increased on postinfection day (PID) 4 during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN-93 attenuated the PRV pain response. These data suggest that CaMKII plays a functional role in pelvic pain due to neurogenic cystitis.


1991 ◽  
Vol 74 (6) ◽  
pp. 916-932 ◽  
Author(s):  
Daniel Jeanmonod ◽  
Marc Sindou

✓ The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a “retuning” of the dorsal horn as the mode of action of MDT is presented.


1996 ◽  
Vol 75 (6) ◽  
pp. 2606-2628 ◽  
Author(s):  
J. T. Katter ◽  
R. J. Dado ◽  
E. Kostarczyk ◽  
G. J. Giesler

1. A goal of this study was to determine whether neurons in the sacral spinal cord that project to the diencephalon are involved in the processing and transmission of sensory information that arises in the perineum and pelvis. Therefore, 58 neurons in segments L6-S2 were activated antidromically with currents < or = 30 microA from points in the contralateral diencephalon in rats that were anesthetized with urethan. 2. Responses to mechanical stimuli applied to the cutaneous receptive fields of these neurons were used to classify them as low-threshold (LT), wide dynamic range (WDR) or high-threshold (HT) neurons. Twenty-two neurons (38%) responded preferentially to brushing (LT neurons). Eighteen neurons (31%) responded to brushing but responded with higher firing frequencies to noxious mechanical stimuli (WDR neurons). Eighteen neurons (31%) responded only to noxious intensities of mechanical stimulation (HT neurons). LT neurons were recorded predominantly in nucleus proprius of the dorsal horn. Nociceptive neurons (WDR and HT) were recorded throughout the dorsal horn. 3. Cutaneous receptive fields were mapped for 56 neurons. Forty-five (80%) had receptive fields that included at least two of the following regions ipsilaterally: the rump, perineum, or tail. Eleven neurons (20%) had receptive fields that were restricted to one of these areas or to the ipsilateral hind limb. Thirty-eight neurons (68%) had cutaneous receptive fields that also included regions of the contralateral tail or perineum. On the perineum, receptive fields usually encompassed perianal and perivaginal areas including the clitoral sheath. There were no statistically significant differences in the locations or sizes of receptive fields for LT neurons compared with nociceptive (WDR and HT) neurons. 4. Thirty-seven LT, WDR, and HT neurons were tested for their responsiveness to heat stimuli. Five (14%) responded to increasing intensities of heat with graded increases in their firing frequencies. Thirty-two LT, WDR, and HT neurons also were tested with cold stimuli. None responded with graded increases in their firing frequencies to increasingly colder stimuli. There were no statistically significant differences among the responses of LT, WDR, and HT neurons to either heat or cold stimuli. 5. Forty LT, WDR, and HT neurons were tested for their responsiveness to visceral stimuli by distending a balloon placed into the rectum and colon with a series of increasing pressures. Seventeen (43%) exhibited graded increases in their firing frequencies in response to increasing pressures of colorectal distention (CrD). None of the responsive neurons responded reproducibly to CrD at an intensity of 20 mmHg, and all responded at intensities of > or = 80 mmHg. More than 90% responded abruptly at stimulus onset, responded continuously throughout the stimulus period, and stopped responding immediately after termination of the stimulus. 6. Thirty-one neurons were tested for their responsiveness to distention of a balloon placed inside the vagina. Eleven (35%) exhibited graded increases in their firing frequencies in response to increasing pressures of vaginal distention (VaD). The thresholds and temporal profiles of the responses to VaD were similar to those for CrD. Twenty-nine neurons were tested with both CrD and VaD. Thirteen (45%) were excited by both stimuli, four (14%) responded to CrD but not VaD, and one (3%) was excited by VaD but not CrD. Neurons excited by CrD, VaD, or both were recorded throughout the dorsal horn. 7. As a population, WDR neurons, but not LT or HT neurons, encoded increasing pressures of CrD and VaD with graded increases in their firing frequencies. The responses of WDR neurons to CrD differed significantly from those of either LT or HT neurons. Regression analyses of the stimulus-response functions of responsive WDR neurons to CrD and VaD were described by power functions with exponents of 1.6 and 2.4, respectively.(ABSTRACT TRUNCATED)


2020 ◽  
Author(s):  
Yunge Jia ◽  
Yinhua Li ◽  
Wei Hou ◽  
Huibing Tan

ABSTRACTNADPH diaphorase (N-d) neurons distribute in spinal cord and function for visceral sensation and autonomic regulation. N-d positive neurons innervate pelvic organs. In previous investigation, we report that aging-related N-d body (ANB) in the lumbosacral spinal cord in aged rat and megaloneurite in the sacral spinal cord in aged dog. This article was a continued data report of aging-related N-d alterations in aged dog. N-d positivity in aged spinal cord has revealed a certain of morphological profiles in the spinal cord of several species. However, we still found some denoted N-d neurodegenerative changes that we failed to notice in our previous studies when re-examination of the sacral spinal cord of aged dog. In the horizontal section, spacing spheroids in the superficial laminae of the dorsal horn, curl-up and coiled neurites in the intermediate zone were detected in the sacral spinal cord. The ANB and vacuolar neurite were also detected. Vacuolar degeneration also occurred in the dorsal ganglia at the sacral segment. The curl-up and coiled neurites did not occur in the lumbothoracic segment, but the ANB and vacuolar neurite were scatteringly detected in in the lumbothoracic segment of aged dog. The results suggested that the N-d sensory inputs interrupted and disconnected with integration of autonomic centers and output circuits of regulating urogenital organs during the aging. These specialized profiles were speculated that the N-d neurite deterioration of visceral sensory circuit implicated dysfunction of pelvic organs in the aging. Megaloneurite and fiber dilation may make backward reasoning to N-d fiber architecture under normal condition.


1999 ◽  
Vol 91 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Marc Guenot ◽  
Jean-Michel Hupe ◽  
Patrick Mertens ◽  
Alan Ainsworth ◽  
Jean Bullier ◽  
...  

Object. In this paper the authors report on the conception and adjustment of a microelectrode used to obtain unitary recordings in the human spinal cord. Methods. To overcome the difficulties related to intraoperative pulsations of the spinal cord, the authors opted to use a floating microelectrode. Because the recordings are obtained most often from spontaneous activities, it is difficult, with a single microelectrode, to separate spikes from electrical artifacts that are related to the switching of devices. Consequently, the authors designed a dual microelectrode made of two tungsten-in-glass—attached microelectrodes separated by 300 µm. Because the two electrodes cannot obtain recordings in the same neuron, it is possible to distinguish unambiguously spikes (recorded on one tip) from electrical artifacts (recorded simultaneously on the two tips). The dual microelectrode is 2 cm long, with a 20-µm tip length, and 800 to 1200—Ohms impedance. This microelectrode can be implanted “free hand,” in the dorsal horn, by using a microsurgical forceps under a surgical microscope. The data analysis is performed off-line with spike sorter hardware. In the dorsal horns in 17 patients who were selected to undergo a dorsal root entry zone (DREZ) rhizotomy to treat various pathological conditions, unitary recordings were obtained using this double microelectrode. The authors recorded 57 neurons in good conditions of stability and isolation. Conclusions. The microelectrode described in this paper was successfully used to obtain recordings in neurons in more than 85% of the patients. This simplified, floating double microelectrode can therefore be considered for use in microsurgical DREZ rhizotomy to obtain unitary recordings in the human spinal dorsal horn.


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