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The results of chronic, in vivo delivery of excitatory and inhibitory neurotransmitter substances upon the craniofacial skeleton are of ongoing interest to clinician and basic scientist alike. Our purpose was to document and compare the effects of biodegradable glycine, glutamate, and thyrotropin-releasing hormone (TRH) microspheres upon the craniofacial skeleton and TMJ of actively growing rats. Glycine, glutamate, TRH, and blank microspheres were stereotactically implanted in proximity to motoneurons within the trigeminal motor nucleus in order to test the following null hypotheses: (1) neurotransmitter microspheres implanted near trigeminal motoneurons of growing rats have no significant effect on the craniofacial skeleton and temporomandibular joints of implanted animals, and (2) there are no significant differences between the relative effects of glutamate, TRH (excitatory to trigeminal motoneurons), and glycine (inhibitory to trigeminal motoneurons) implants upon the craniofacial skeleton and temporomandibular joint. Fifty male Sprague-Dawley rats underwent stereotactic neurosurgery at 35 days; five rats each were killed at 14 and 21 days postoperative for data collection and comparison between glycine-, glutamate-, TRH-, blank-microsphere, and sham-surgery rats. Glycine rats had significantly (P < or = 0.05, 0. 01) smaller implant-side cranial dimensions and mandibular condyles, all glycine rats showed increased gracility of implant-side bones, and deviation of their facial skeleton away from the implant-side; this was in contrast to the generally larger implant-side bony structures in both glutamate and TRH rats. The two null hypotheses were both rejected. Due to their inhibitory and excitatory effects upon trigeminal motoneurons, masticatory muscles, and their neuromuscular generation of biomechanical forces that affect bone, the neurotransmitter substances glycine, glutamate, and TRH appear to play an important role in the growth and development of the mammalian craniofacial skeleton and TMJ., (Copyright 2000 Wiley-Liss, Inc.)

Earlier work has shown that two important consequences of implanting thyrotropin-releasing hormone (TRH) microspheres near motoneurones within the trigeminal motor nucleus of actively growing rats are increased muscle mass and a darkening of the implant-side masticatory muscles. These phenomena have been associated with altered neuromuscular activity patterns and biomechanical forces that directly influence craniofacial growth and development. Now, whether the implantation of TRH microspheres in proximity to trigeminal motoneurones would affect the oxidative capacity of the implant-side masseter muscles was investigated. Cytochrome C oxidase (COX) assays were carried out for both implant- and non-implant-side masseters of TRH (n = 5) and blank microsphere (n = 6) Sprague-Dawley rats after stereotactic surgery at 35 days of age. Analyses of both groups at 14 days post-implantation revealed that the COX activity levels of implant-side masseters in TRH-implanted rats was significantly (P< or =0.05) greater than that of non-implant-side masseters; rats implanted with blank microsphere exhibited no significant difference between implant- and non-implant-side masseter COX activity levels. The stated null hypothesis was therefore rejected. These data suggest that TRH implants in proximity to trigeminal motoneurones effect increased oxidative capacity of the masseter muscle as measured by COX activity.

Stereotaxic surgery was performed on the trigeminal motor nuclei (TMNu) of 47 actively growing rats in order to test the effects of neuromuscular alterations on TMJ disc morphology. Lesioned animals received a small electrolytic lesion to their left-side TMNu, while shams had their TMNu stimulated without an actual lesion being produced. Both lesioned and sham-lesioned animals demonstrated significant (P less than 0.05; P less than 0.01) morphological alterations of their discs 28, 56, and 84 days postoperatively. Data indicated that (i) TMNu lesions do indeed affect disc morphology, and (ii) even subtle damage to trigeminal motoneurones can influence TMJ disc morphology. It is therefore suggested that at least some TMJ disease processes have a neuromuscular basis.

Unilateral electrolytic lesions were made in the left-side facial motor nucleus (FMNu) of six Sprague-Dawley rats at 35 days of age in order to correlate craniofacial sequelae with changed motoneuron function. Experimental and control rats were killed at 22, 32, 42, and 52 days postoperatively to provide muscle weight, brain histology, and dry skull preparations for analyses. Dissection, muscle weight, motoneuron count, and osteometric data revealed that lesion-side facial and masticatory muscles were affected by the lesions. Paired t-tests indicated that significant differences existed between weights of experimental lesion- and nonlesion-side anterior digastric, temporalis, masseteric complex, and medial pterygoid muscles, numbers of facial and trigeminal motoneurons, and several skeletal dimensions of the skull. Basi-cranial dimensions of experimental animals were least affected by the lesion, whereas zygomatic arch, dorsal facial region, and mandibular condyle dimensions were most affected. Statistical analyses also detected significant differences between experimental and control groups for several skeletal dimensions of the skull. Data indicated that damage to the trigeminal motor nucleus (TMNu) was secondary to the primary lesion in the FMNu. Motoneurons within the facial and trigeminal neuromuscular complexes (FNC and TNC) play an important role in craniofacial growth and development.

Although the role of serotonin (5-hydroxytryptamine or 5-HT) in pre-natal craniofacial growth and development has been studied, no research has been done on the effects of serotonin on post-natal craniofacial growth and development. The following experimental question was tested: What effect does increasing in vivo serotonin levels adjacent to trigeminal motoneurons have on post-natal craniofacial structures in young, actively growing rats? Forty male Sprague-Dawley rats were divided into 4 experimental groups (10% serotonin microspheres, 15% serotonin microspheres, blank microspheres, sham surgeries) and underwent stereotactic neuro-surgery at post-natal day 35; 5 rats of each group were killed at 14 and 21 post-surgical days for data collection. Statistical analyses by mixed-model, 4 x 2 repeated-measures ANOVA, and post hoc Fisher LSD tests revealed significant (P ≤ 0.05, 0.01) differences between groups and sides for muscle weight, cranial dimension, and TMJ dimension data. Data described here indicate that significant alterations of post-natal craniofacial structures can be caused by altered in vivo levels of serotonin adjacent to trigeminal motoneurons. [ABSTRACT FROM AUTHOR]

The sequelae of sustained, in vivo delivery of two important neurotransmitter substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial growth and development have previously not been investigated. Our purpose was to document and compare the relative effects of glutamate and TRH microspheres stereotactically placed in proximity to trigeminal motoneurons within the trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH microspheres in proximity to trigeminal motoneurons have no significant effect upon the craniofacial skeleton, and (2) there are no significant differences between the relative effects of chronic, long-term delivery of glutamate and TRH upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley rats were divided into 4 experimental groups (glutamate microspheres, TRH microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for data collection. Histology revealed that implants were clustered in the pontine reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate and TRH rats had implant-side deviation of their facial skeleton and snout regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P ≤ 0.05, 0.01) differences between groups and sides for motoneuron count, muscle weight, and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs and mandibular fossae in comparison with the other groups. The stated null hypotheses were therefore rejected. [ABSTRACT FROM AUTHOR]