ABSTRACT
BACKGROUND/AIMS: Stress exacerbates neuron loss in many CNS injuries via the actions of adrenal glucocorticoid (GC) hormones. For some injuries, this GC endangerment of neurons is accompanied by greater immune cell activation in the CNS, a surprising outcome given the potent immunosuppressive properties of GCs. METHODS: To determine whether the effects of GCs on inflammation contribute to neuron death or result from it, we tested whether nonsteroidal anti-inflammatory drugs could protect neurons from GCs during kainic acid excitotoxicity in adrenalectomized male rats. We next measured GC effects on (1) chemokine production (CCL2 and CINC-1), (2) signals that suppress immune activation (CX3CL1, CD22, CD200, and TGF-ß), and (3) NF-κB activity. RESULTS: Concurrent treatment with minocycline, but not indomethacin, prevented GC endangerment. GCs did not substantially affect CCL2, CINC-1, or baseline NF-κB activity, but they did suppress CX3CL1, CX3CR1, and CD22 expression in the hippocampus - factors that normally restrain inflammatory responses. CONCLUSIONS: These findings demonstrate that cellular inflammation is not necessarily suppressed by GCs in the injured hippocampus; instead, GCs may worsen hippocampal neuron death, at least in part by increasing the neurotoxicity of CNS inflammation.
Subject(s)
Excitatory Amino Acid Agonists/toxicity , Glucocorticoids/metabolism , Hippocampus/drug effects , Hippocampus/immunology , Kainic Acid/toxicity , Adrenalectomy , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Death/drug effects , Cell Death/physiology , Chemokines/metabolism , Dose-Response Relationship, Drug , Hippocampus/pathology , Indomethacin/pharmacology , Male , Minocycline/pharmacology , Neuroimmunomodulation/drug effects , Neuroimmunomodulation/physiology , Neurons/drug effects , Neurons/immunology , Neurons/pathology , Neuroprotective Agents/pharmacology , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Cleft lip and palate surgery in the developing child is known to be associated with maxillary hypoplasia. However, the effects of nonsurgical manipulations on maxillary growth have not been well investigated. The authors present the contribution of orthodontic dental space closure with canine substitution to maxillary hypoplasia and the need for orthognathic surgery. METHODS: Cleft lip/palate and cleft palate patients older than 15 years of age were reviewed for dental anomalies, orthodontic canine substitution, and Le Fort I advancement. Skeletal relationships of the maxilla to the skull base (SNA), mandible (ANB), and facial height were determined on lateral cephalograms. Logistic regression analyses were performed to estimate odds ratios. RESULTS: Ninety-five patients were reviewed (mean age, 18.1 years). In 65 patients with congenitally missing teeth, 55 percent with patent dental spaces required Le Fort I advancement. In contrast, 89 percent who underwent canine substitution required Le Fort I advancement (p = 0.004). Canine substitution is associated with a statistically significant increase in maxillary retrognathia when compared with dental space preservation on lateral cephalograms (mean SNA, 75.2 and 79.0, respectively; p = 0.006). Adjusting for missing dentition, logistic regression analyses demonstrated that canine substitution is an independent predictor for orthognathic surgery (OR, 6.47) and maxillary retrusion defined by SNA < 78 (OR, 8.100). CONCLUSIONS: The coordination of orthodontia and surgery is essential to cleft care. The authors report a strong association between orthodontic cleft closure using canine substitution with maxillary hypoplasia and subsequent Le Fort I advancement, and suggest systematic criteria for management of cleft-related dental agenesis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
Subject(s)
Cleft Lip/complications , Cleft Palate/complications , Maxilla/abnormalities , Micrognathism/therapy , Orthodontic Space Closure , Orthognathic Surgical Procedures , Adolescent , Female , Humans , Male , Retrospective Studies , Young AdultABSTRACT
A possible avenue to improve the clinical success of bone graft procedures in cleft lip and palate cases is to predetermine the bone donor site and the volume of graft material required for the recipient site. This study utilized cone beam computed tomography to generate three-dimensional reconstructions and volumetrically assess unilateral cleft lip and palate defects. Access to this information can assist in determining an optimal donor site for secondary alveolar bone grafting.
