RESUMEN
Limb denervation leads to reorganization of the representational zones of the somatosensory cortex. Using [11C](R)-PK11195, a sensitive in vivo marker of glial cell activation, and PET, we provide first evidence that limb denervation induces a trans-synaptic increase in [11C](R)-PK11195 binding in the human thalamus but not somatosensory cortex: these brain structures appeared morphologically normal on magnetic resonance imaging (MRI). The increased thalamic signal was detectable many years after nerve injury, indicating persistent reorganization of the thalamus. This glial activation, beyond the first-order projection area of the injured neurons, may reflect continually altered afferent activity. Our findings support the view that long-term rearrangement of cortical representational maps is significantly determined within the thalamus.
Asunto(s)
Neuroglía/fisiología , Traumatismos de los Nervios Periféricos , Sinapsis/fisiología , Tálamo/fisiopatología , Adulto , Amputación Traumática/metabolismo , Amputación Traumática/fisiopatología , Sitios de Unión , Femenino , Humanos , Isoquinolinas/metabolismo , Masculino , Persona de Mediana Edad , Neuroglía/metabolismo , Plasticidad Neuronal/fisiología , Nervios Periféricos/metabolismo , Receptores de GABA-A/análisis , Sinapsis/metabolismo , Tálamo/metabolismo , Factores de Tiempo , Tomografía Computarizada de Emisión/métodosRESUMEN
UNLABELLED: Following traumatic limb amputation it is common clinical practice to maintain the ischemic tissues in a hypothermic state until surgical reimplantation. Of all extremity tissues, muscle is the most sensitive to ischemia; it is therefore imperative that reperfusion be established before diffuse muscle necrosis. Although it has been shown both clinically and experimentally that hypothermia prolongs the viability of ischemic skeletal muscle, the presumed mechanism by which this occurs has not been confirmed at the cellular level. This study was undertaken to quantify the effect of conventional iced-saline hypothermia on anaerobic cell metabolism and high-energy phosphate depletion in traumatically devascularized muscle. METHODS: Phosphorus nuclear magnetic resonance spectroscopy (31P NMR) was employed to noninvasively monitor cellular phosphocreatine (PCr), ATP, and intracellular pH over time in ischemic cat hindlimb muscle under room temperature (22 degrees C) and 1 degree C hypothermic conditions. RESULTS: Muscular PCr depletion was significantly retarded by tissue hypothermia but the rate of ATP depletion was not. A progressive, severe cellular acidosis was observed in the room-temperature muscle. Iced tissue cooling produced a dramatic initial rise in cell pH which significantly reduced the absolute degree of subsequent acidotic changes. SIGNIFICANCE: These findings question our understanding of hypothermic tissue preservation, which has generally been assumed to work on the basis of decreased tissue metabolism, thus conserving critical cellular ATP levels. The empirical benefit derived by cooling muscle in an iced medium may actually be related to the cellular alkalinization produced by tissue cooling, as this significantly mitigates the profound acidosis that would otherwise occur.