ABSTRACT
Intracranial surgery causes brain damage from cortical incisions, intraoperative hemorrhage, retraction, and electrocautery; collectively these injuries have recently been coined surgical brain injury (SBI). Inflammation following SBI contributes to neuronal damage. This study develops T-cells that are immunologically tolerant to brain antigen via the exposure of myelin basic protein (MBP) to airway mucosa. We hypothesize that these T-cells will migrate to the site of corticotomy, secrete immunosuppressive cytokines, such as TGFß1, reduce inflammation, and improve neurological outcomes following SBI. A standard model for SBI was used for this experiment. C57 mice were divided into six groups: SHAM+Vehicle, SHAM+Ovalbumin, SHAM+MBP, SBI+Vehicle, SBI+OVA, and SBI+MBP. Induction of mucosal tolerance to vehicle, ovalbumin, or MBP was performed prior to SBI. Neurological scores and TBFß1 cytokine levels were measured 48 h postoperatively. Mice receiving craniotomy demonstrated a reduction in neurological score. Animals tolerized to MBP (SBI+MBP) had better postoperative neurological scores than SBI+Vehicle and SBI+OVA. SBI inhibited the cerebral expression TGFß1 in PBS and OVA treated groups, whereas MBP treated-animals preserved preoperative levels. Mucosal tolerance to MBP leads to significant improvement in neurological outcome that is associated with the preservation of endogenous levels of brain TGFß1.
Subject(s)
Brain Injuries/etiology , Brain Injuries/pathology , Craniotomy/adverse effects , Mucous Membrane/immunology , Transforming Growth Factor beta1/metabolism , Analysis of Variance , Animals , Brain/immunology , Brain/metabolism , Brain/pathology , Brain Injuries/complications , Brain Injuries/therapy , Disease Models, Animal , Drug Tolerance/immunology , Inflammation/etiology , Mice , Mice, Inbred C57BL , Mucous Membrane/drug effects , Myelin Basic Protein/immunology , Neurologic Examination , Ovalbumin/therapeutic use , Transforming Growth Factor beta1/immunology , Treatment OutcomeABSTRACT
PURPOSE: Prior to implantation of a sacral neuromodulator we carried out PNE tests (peripheral nerve evaluation test) with bilateral test stimulation to establish which patients might profit from this kind of therapy. In contrast to the original unilateral technique used by Tanagho and Schmidt, we performed bilateral PNE test stimulation. Moreover, we analysed the diagnostic characteristics of those patients who had positive PNE test results and could thus receive a chronic sacral neuromodulator. MATERIALS AND METHODS: We performed bilateral PNE test stimulation in 70 patients (mean age: 53.6 yrs; 41 with retention symptoms and 29 with a hyperactive detrusor) over a minimum of 3 days. Retrospectively, we analysed the distribution of diagnostic characteristics (retention vs. overactive bladder and neurogenic vs. idiopathic) in the implant recipients. RESULTS: All patients received bilateral PNE test stimulation, during which the stimulation amplitudes were adjusted individually for each side. 8 patients were treated with the original PNE-electrode (model 0 041 830 - 002, Medtronic Inc., USA) without success. Of the remaining 62 patients, who were treated with an improved electrode, the PNE test was successful in 32 cases (51.6 %). Twenty-seven of these patients suffered from a neurogenic bladder dysfunction, and, in 5 cases, the causes were idiopathic. CONCLUSIONS: Bilateral PNE-test stimulation and the use of advanced PNE electrodes (model 3057, Medtronic Inc., USA) led to a positive PNE result in 51.6 % of the tested patients. Of these, the group with neurogenic bladder dysfunctions showed the highest response rate. Compared with the success rates in the multicenter study, we were able to increase the overall PNE response rate significantly. For this reason, we prefer a bilateral PNE-test with side-specific stimulation.
