A new method for modulating traumatic brain injury with mechanical tissue resuscitation.
ABSTRACT Traumatic brain injuries remain a treatment enigma with devastating late results. As terminally differentiated tissue, the brain retains little capacity to regenerate, making early attempts to preserve brain cells after brain injury essential.
To resuscitate damaged tissue by modulating edema, soluble cytokines, and metabolic products in the "halo" of damaged tissue around the area of central injury that progressively becomes compromised. By re-equilibrating the zone of injury milieu, it is postulated neurons in this area will survive and function.
Mechanical tissue resuscitation used localized, controlled, subatmospheric pressure directly to the area of controlled cortical impact injury and was compared with untreated injured controls and with sham surgery in a rat model. Functional outcome, T2 magnetic resonance imaging hyperintense volume, magnetic resonance imaging spectroscopy metabolite measurement, tissue water content, injury cavity area, and cortical volume were compared.
There were significant differences between mechanical tissue resuscitation treated and untreated groups in levels of myoinositol, N-acetylaspartate, and creatine. Treated animals had significantly less tissue swelling and density than the untreated animals. Nonviable brain tissue areas were smaller in treated animals than in untreated animals. Treated animals performed better than untreated animals in functional tests. Histological analysis showed the remaining viable ipsilateral cerebral area was 58% greater for treated animals than for untreated animals, and the cavity for treated animals was 95% smaller than for untreated animals 1 month after injury.
Mechanical tissue resuscitation with controlled subatmospheric pressure can significantly modulate levels of excitatory amino acids and lactate in traumatic brain injury, decrease the water content and volume of injured brain, improve neuronal survival, and speed functional recovery.
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ABSTRACT: Traumatic brain injuries (TBI) continue to be a devastating problem with limited treatment options. Previous research applying controlled vacuum to TBI in a rat model resulted in smaller injuries and more rapid recovery. To examine the effects of application of controlled vacuum (mechanical tissue resuscitation) to TBI in a large animal model. Magnitude of vacuum, length of application, and length of delay between injury and application of mechanical tissue resuscitation were investigated. Localized, controlled cortical injuries (CCI) were created in swine. Vacuums of -50 and -100 mm Hg were compared. Mechanical tissue resuscitation for 3 or 5 days was compared. Delays of 0, 3, or 6 hours between creation of the TBI and initiation of mechanical tissue resuscitation were examined. Analysis included histological assessments, CT perfusion, and MR imaging (T2, proton-magnetic spectra). 100 mm Hg vacuum resulted in significantly smaller mean contused brain and hemorrhage volumes compared with -50 mm Hg and controls. MR spectra of treated animals returned to near baseline values. All 10 animals with 5-day mechanical tissue resuscitation treatment survived. Three of 6 animals treated 3 days died after discontinuation of treatment. A 3-hour delay resulted in similar results as immediate treatment. A 6-hour delay produced significant, but lesser responses. Application of mechanical tissue resuscitation to TBI was efficacious in the large animal model. Application of -100 mm Hg for 5 days resulted in significantly improved outcomes. Delays of up to 3 hours between injury and initiation of treatment did not diminish efficacy of the mechanical tissue resuscitation treatment.Neurosurgery 03/2014; 75(2). DOI:10.1227/NEU.0000000000000341 · 3.03 Impact Factor
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ABSTRACT: Reperfusion injury is a complex inflammatory response involving numerous mechanisms and pathways. Mechanical tissue resuscitation is a newly described therapeutic strategy that reduces reperfusion injury. This study further investigates potential mechanisms for the protective effects of mechanical tissue resuscitation while utilizing a bio-absorbable matrix. Anesthetized swine were subjected to 80 minutes of coronary ischemia and three hours of reperfusion. An absorbable matrix was used to cover the ischemic-reperfused myocardium and apply the mechanical tissue resuscitation (-50 mmHg) throughout reperfusion. Infarct size, myocardial blood flow (microspheres), apoptosis, edema, and hemodynamics were analyzed. Both control and treated groups displayed similar hemodynamics and physiologic parameters. Mechanical tissue resuscitation significantly reduced early infarct size (16.6 ± 3.8% vs. 27.3 ± 2.5% of area at risk, p < 0.05). This reduction of infarct size was accompanied by reduced edema formation in both epicardial (27% reduction) and endocardial (58% reduction) samples. Histological examination of both epicardial and endocardial tissues also revealed a reduction in apoptosis (80% and 44% reductions) in MTR-treated hearts. Treatment with mechanical tissue resuscitation during reperfusion reduces both early cell death and the delayed, programmed cell death after ischemia-reperfusion. This cardioprotection is also associated with a significant reduction in interstitial water. Additional cardioprotection may be derived from mechanical tissue resuscitation-induced increased blood flow. Mechanical tissue resuscitation, particularly with a resorbable device, is a straightforward and efficacious mechanical strategy for decreasing cardiomyocyte death following myocardial infarction as an adjunctive therapy to surgical revascularization.Journal of Cardiac Surgery 11/2013; 29(1). DOI:10.1111/jocs.12247 · 0.89 Impact Factor
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ABSTRACT: Neurobehavioral assessment of outcome has played an integral part in traumatic brain injury (TBI) research. Given the fundamental role of neurobehavioral measurement, it is critical that the tasks used are of the highest psychometric quality. The purpose of this paper is to evaluate several, commonly used neurobehavioral measures along the dimensions of reliability, sensitivity, and validity. Using both the midline and lateral fluid-percussion injury models, nine neurobehavioral measures were evaluated that assessed three different neurobehavioral constructs. Reflex suppression was measured by the duration of the suppression of the pinna, corneal, and righting reflexes. Vestibulomotor function was assessed with the beam-balance, beam-walking, and rotorod tasks. Cognitive function was evaluated by three measures of Morris water maze performance (goal latency, path length, cumulative distance). The evaluation of the reliability of the nine neurobehavioral measures found that all had acceptably high reliability coefficients (0.79 or higher). The analysis of each measure's sensitivity to injury found that all measures were capable of detecting injury-induced impairments. However, there were some substantial differences in the sensitivity of the measures of vestibulomotor and maze performance: the rotorod was the most sensitive vestibulomotor measure and goal latency and path length were equally sensitive measures of maze performance. In the assessment of validity, the results of a factor analysis supported the convergent and discriminative validity of the measures. And in cases in which the preclinical and clinical research have assessed the same construct, the animal model neurobehavioral measures had predictive (or external) validity. Thus, according to the psychometric standards by which measurement instruments are evaluated, the results indicated that these measures provide a valid assessment of neurobehavioral function after fluid percussion TBI.Journal of Neurotrauma 12/2001; 18(11):1207-16. DOI:10.1089/089771501317095241 · 3.97 Impact Factor