The timing of acid-induced increase in saliva secretion in transplanted submandibular glands

Liu, X.J.; Li, M.; Su, Jia-Zeng; Xie, Zheng; Yu, Guang‐Yan

doi:10.1016/j.ijom.2015.01.003

Cited by 3 publications

(5 citation statements)

References 20 publications

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“…At 6 months after denervation, autonomic axon density had recovered to the control level, the impaired gland structure was greatly relieved, and the resting salivation was doubled. Meanwhile, stimulated salivation had recovered, which has also been observed in some patients who underwent SMG transplantation (Liu, Li, Su, Xie, & Yu, 2015). These results suggest that reinnervation contributes, at least in part, to the regeneration process and the response to citric acid in long-term recovery after parasympathectomy.…”

Section: The Reinnervation Of Smgs After Parasympathectomy In the Lon...supporting

confidence: 62%

Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term

Zhang

Huang

Cong

et al. 2018

Journal Cellular Physiology

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Parasympathectomy leads to retrogressive alteration and dysfunction of the submandibular gland (SMG) within 1 month, but its long‐term effect is unclear. Excessive secretion is observed in half of the patients 4–6 months after SMG transplantation, which completely denervates the gland. Here, we investigated the long‐term effect of parasympathectomy on the secretion of SMGs in minipigs. The results showed that the resting salivary secretion of SMGs decreased by 82.9% of that in control at 2 months after denervation, but increased by 156% at 6 months. Although experiencing an atrophic period, the denervated glands regained their normal morphology by 6 months. The expression of the function‐related proteins, including muscarinic acetylcholine receptor (mAChR) 3, aquaporin 5 (AQP5), tight junction protein claudin‐3, and claudin‐4 was decreased at 2 months after denervation. Meanwhile, the protein expression of stem cell markers, including sex‐determining region Y‐box 2 and octamer‐binding transcription factor 4, and the number of Ki67+ cells were significantly increased. However, at 6 months after denervation, the expression of mAChR3, AQP5, claudin‐1, claudin‐3, and claudin‐4 was significantly raised, and the membrane distribution of these proteins was increased accordingly. The autonomic axonal area of the glands was reduced at 2 months after denervation but returned to the control level at 6 months, suggesting that reinnervation took place in the long term. In summary, parasympathectomy increases resting secretion of the SMGs in the long term with a possible mechanism involving improved transepithelial fluid transport. This finding may provide a new strategy for xerostomia treatment.

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Section: The Reinnervation Of Smgs After Parasympathectomy In the Lon...supporting

confidence: 62%

Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term

Zhang

Huang

Cong

et al. 2018

Journal Cellular Physiology

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“…The auriculotemporal nerve, which rules the secretion of parotid gland, is usually exposed in the recipient bed during the transplantation surgery, and its location anatomically correspond to our results that large cholinergic nerve trunks were observed in the temporal fascia lower to the gland. Our previous work has demonstrated acid stimulated secretion in some epiphora patients’ glands with proper cholinergic innervation by 99m Tc scintigraphy, 36 which backs up the origin from auriculotemporal nerve since there exits an olfactory salivary reflex in these cases.…”

Section: Discussionmentioning

confidence: 92%

Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca

et al. 2018

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Autologous submandibular gland (SMG) transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously. This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients’ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.

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“…In patients undergoing primary surgery, median time was 32 days (IQR, and in patients undergoing primary nonsurgical therapy, median time was 46.5 days (IQR, [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]. Time from tissue diagnosis to SMGT was 28 days (IQR, 21-44), and from surgery to adjuvant therapy was 33 days (IQR, [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. Thirteen patients suffered a treatment delay: seven patients due to >60 days from diagnosis to treatment initiation (7/49; 14%) and six due to >6 weeks from surgery to adjuvant radiation (6/19; 32%).…”

Section: Resultsmentioning

confidence: 99%

“…Forty-two percent of patients receive >39 Gy. 33,34 Other reports demonstrate that IMRT only reduces the SMG dose to [35][36][37][38][39][40][41][42][43][44][45] Gy. [35][36][37] It has been recommended that doses beyond 25 Gy should be avoided if significant salivary function is to be preserved.…”

Section: Discussionmentioning

confidence: 99%

“…20 Liu et al used sodium pertechnetate salivary gland scintigraphy and observed significantly improved trapping and excretion function at >6 months after transplantation, suggesting that parasympathetic reinnervation may occur. 40 SMGT also provides the additional benefit of allowing intraoperative assessment of the status of nodes encountered in level I, which can be valuable additional information when planning either definitive or adjuvant RT.…”

Section: Discussionmentioning

confidence: 99%

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Implementation of submandibular gland transfer: A multi‐institutional study of feasibility and time to treatment

et al. 2019

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Background: Submandibular gland transfer (SMGT) mitigates radiation-induced xerostomia but has yet to be widely adopted. We evaluate the feasibility of incorporating SMGT at multiple academic institutions and report the incidence of treatment delay. Methods: Forty-nine patients were identified who underwent SMGT. Time points pertaining to diagnosis and key treatment events including SMGT, surgery, chemotherapy, and radiation were extracted. Treatment delay was defined as either >60 days from diagnosis to definitive therapy or >6 weeks between surgery and adjuvant therapy.

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The timing of acid-induced increase in saliva secretion in transplanted submandibular glands

Cited by 3 publications

References 20 publications

Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term

Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term

Autonomic reinnervation and functional regeneration in autologous transplanted submandibular glands in patients with severe keratoconjunctivitis sicca

Implementation of submandibular gland transfer: A multi‐institutional study of feasibility and time to treatment

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