Developmental and injury induced plasticity in the micturition reflex pathway

Transplanting neuronal and glial restricted precursors (NRP/GRP) into a midthoracic injury 9 d after contusion improved bladder and motor function, diminished thermal hypersensitivity, and modified lumbosacral circuitry compared with operated controls (OPcontrols). Histological analysis showed that NRP/GRP survived, filled the lesion site, differentiated into neurons and glia, and migrated selectively. Volume of spinal cord spared was increased in NRP/GRP recipients, suggesting local protection. Bladder areflexia developed in both operated groups, but NRP/GRP recipients exhibited an accelerated recovery, with decreased micturition pressure and fewer episodes of detrusor hyperreflexia. Because noradrenergic receptors proliferate after spinal injury and descending noradrenergic pathways contribute to regulation of bladder control, we examined the effects of administering an ␣-1A-adrenergic antagonist, Tamsulosin, on urodynamics. This improved all cystometric parameters in both operated groups, and micturition pressure in NRP/GRP rats recovered to normal levels. Both operated groups initially showed increased sensitivity to a thermal stimulus applied to the tail; the NRP/GRP rats showed significant improvement over time. NRP/GRP grafts also produced greater recovery of hindlimb function in several tests, although both groups showed persistent and similar deficits in locomotion on a grid.Because bladder, hindlimb, and tail sensory and motor functions are organized through lumbosacral cord, we examined descending and primary afferent projections at L6 -S1. The density of serotonergic, noradrenergic, and corticotrophin releasing factor-positive fibers increased in the NRP/GRP group compared with OP-controls, suggesting some sparing and/or sprouting of these modulatory pathways. Immunocytochemical staining density of dorsal root axons in the dorsal horn increased in the OP-controls but appeared normal in the NRP/GRP group. Synaptophysin immunoreactivity in the lumbosacral dorsal horn was similar among groups, consistent with restoration of synaptic density in both groups of operated animals but by different pathways. We suggest that local protection provided by NRP/GRP resulted in increased sparing/sprouting of descending pathways, which prevented sprouting by dorsal root axons, and that this modification in lumbosacral circuitry contributes to the recovery of function.

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“…7B). Thus VR-1-IR axons sprouted in the DH of OP-controls, as described previously (de Groat et al, 1990(de Groat et al, , 1998Zhou et al, 2002).…”

Section: Reorganization In Lumbosacral Spinal Cordsupporting

confidence: 58%

Transplantation of Neuronal and Glial Restricted Precursors into Contused Spinal Cord Improves Bladder and Motor Functions, Decreases Thermal Hypersensitivity, and Modifies Intraspinal Circuitry

Mitsui¹,

Shumsky²,

Lepore³

et al. 2005

J. Neurosci.

169

187

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“…The emergence of faster activity in bladders from older animals may reflect the development of multiple pacemaker sites, which would reduce coordination within the bladder wall and improve storage function in the mature bladder. spontaneous contractions; fast Fourier transformation; nonlinear analysis IN NEONATAL ANIMALS during the early postnatal period, micturition is mediated by a somatobladder spinal reflex pathway, which is activated when the mother licks the perineum of the neonate (3,5,6,14,17,22,25,27). During postnatal development this primitive reflex is replaced by supraspinal mechanisms, which underlie the mature bladder-to-bladder reflex and voluntary voiding (1,5,11,12,14).…”

mentioning

confidence: 99%

“…spontaneous contractions; fast Fourier transformation; nonlinear analysis IN NEONATAL ANIMALS during the early postnatal period, micturition is mediated by a somatobladder spinal reflex pathway, which is activated when the mother licks the perineum of the neonate (3,5,6,14,17,22,25,27). During postnatal development this primitive reflex is replaced by supraspinal mechanisms, which underlie the mature bladder-to-bladder reflex and voluntary voiding (1,5,11,12,14). In the rat, this developmental change in the central neural control of voiding occurs in concert with changes in peripheral neurotransmission and intrinsic properties of the bladder smooth muscle (13,14,24,25).…”

mentioning

confidence: 99%

“…On the other hand, in bladders from neonatal animals older than 3 wk of age and from adult animals, spontaneous contractions are of low amplitude at body temperature and increase in amplitude at lower temperatures. This dramatic change in temperature sensitivity occurs during the developmental period when central micturition pathways are maturing (1,5,11,12,14). Thus under physiological conditions the neonatal bladder is capable of generating large-amplitude intrinsic contractions, which presumably reflect pacemaker activity and efficient mechanisms for conducting this activity throughout the bladder (22,24).…”

mentioning

confidence: 99%

“…During postnatal development this primitive reflex is replaced by supraspinal mechanisms, which underlie the mature bladder-to-bladder reflex and voluntary voiding (1,5,11,12,14). In the rat, this developmental change in the central neural control of voiding occurs in concert with changes in peripheral neurotransmission and intrinsic properties of the bladder smooth muscle (13,14,24,25).…”

mentioning

confidence: 99%

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Developmental changes in spontaneous smooth muscle activity in the neonatal rat urinary bladder

Széll¹,

Somogyi²,

Groat³

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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Szé ll, Enikő A., George T. Somogyi, William C. de Groat, and Gyula P. Szigeti. Developmental changes in spontaneous smooth muscle activity in the neonatal rat urinary bladder. Am J Physiol Regul Integr Comp Physiol 285: R809-R816, 2003. First published May 15, 2003 10.1152/ ajpregu.00641.2002.-Changes in spontaneous activity of the urinary bladder during postnatal development were examined in muscle strips from the base and dome of bladders from 1-to 5-wk-old rats. Activity was analyzed using fast Fourier transformation (FFT), nonlinear cross prediction, and the Shannon entropy test. Spontaneous activity was not detected in strips from 1-to 5-day-old rats but was observed in 50% of strips from 6-to 7-day-old rats and was prominent in strips from 2-wk-old animals. FFT analysis revealed one peak in activity, which was significantly faster in the bladder base (0.21 Ϯ 0.03 Hz) than in the dome (0.08 Ϯ 0.01 Hz). A second peak at ϳ0.5 Hz was detected at 3-5 wk of age. Atropine but not tetrodotoxin decreased the amplitude of spontaneous contractions, whereas carbachol, a muscarinic agonist, unmasked or stimulated spontaneous activity. These data suggest that slow rhythmic activity observed previously in neonatal whole bladders is generated by pacemaker cells in the bladder base or dome. The emergence of faster activity in bladders from older animals may reflect the development of multiple pacemaker sites, which would reduce coordination within the bladder wall and improve storage function in the mature bladder. spontaneous contractions; fast Fourier transformation; nonlinear analysis IN NEONATAL ANIMALS during the early postnatal period, micturition is mediated by a somatobladder spinal reflex pathway, which is activated when the mother licks the perineum of the neonate (3,5,6,14,17,22,25,27). During postnatal development this primitive reflex is replaced by supraspinal mechanisms, which underlie the mature bladder-to-bladder reflex and voluntary voiding (1,5,11,12,14). In the rat, this developmental change in the central neural control of voiding occurs in concert with changes in peripheral neurotransmission and intrinsic properties of the bladder smooth muscle (13,14,24,25). The latter have been demonstrated in whole bladder preparations (14,15,(22)(23)(24)(25) in vitro and in bladder strips (13) of the neonatal rat. Whole bladders removed from pups during the first postnatal week exhibit low-amplitude spontaneous contractions. These contractions increase in amplitude during the second and third postnatal week (13,22,23). In bladder strips, spontaneous activity was absent during the first week but was detectable during the second postnatal week (13).Excitatory and inhibitory neural mechanisms also change during development (1,22,23,25). For example, neurally evoked bladder contractions were mediated entirely by cholinergic mechanisms in the bladder strips from 1-wk-old rats but became primarily purinergic in strips obtained from 2-wk-old animals (13,14). Inhibitory neural mechanisms driven by tonic outflow from th...

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Bladder contractility‐related neurons in barrington's nucleus: Axonal projections to the spinal cord in the cat

Sasaki

2002

J of Comparative Neurology

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Barrington's nucleus projects directly to the sacral parasympathetic nucleus. The purpose of this study was to clarify whether neurons in Barrington's nucleus that increase their firing during bladder contractions project to the spinal cord and, if so, to which level(s) the axon reaches. Single units were recorded in Barrington's nucleus of cat with glass microelectrodes, and the termination level of descending axons was determined by antidromic stimulation of the spinal cord. Thirty-nine neurons projecting to the spinal cord were located in rostral parts of the dorsolateral pontine tegmentum, medial and ventral to the mesencephalic trigeminal tract. This finding is consistent with previous neuronal tracing studies. All neurons increased their firing rates during contraction associated with micturition. In 19 examined neurons, the most caudal level of the descending axon distributed between the L7 and the S3 level. Stimulation of the axon at this most caudal level resulted in antidromic spike latencies ranging between 19.5 msec and 45.0 msec. These antidromic latencies were much smaller than previously reported orthodromic conduction times between neurons in Barrington's nucleus and sacral preganglionic neurons innervating the bladder. The mean conduction velocity of the descending axon from the cell body to the border between Th13 and the L1 ranged between 7.2 m/sec and 27.7 m/sec. The decrease of the mean conduction velocity was observed at the lumbar as well as at the sacral segments, suggesting that axons issue collaterals to the lumbar level as well as to the sacral level.

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Developmental and injury induced plasticity in the micturition reflex pathway

Cited by 203 publications

References 54 publications

Transplantation of Neuronal and Glial Restricted Precursors into Contused Spinal Cord Improves Bladder and Motor Functions, Decreases Thermal Hypersensitivity, and Modifies Intraspinal Circuitry

Transplantation of Neuronal and Glial Restricted Precursors into Contused Spinal Cord Improves Bladder and Motor Functions, Decreases Thermal Hypersensitivity, and Modifies Intraspinal Circuitry

Developmental changes in spontaneous smooth muscle activity in the neonatal rat urinary bladder

Bladder contractility‐related neurons in barrington's nucleus: Axonal projections to the spinal cord in the cat

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