0000000000154079
AUTHOR
M. Ross Bullock
The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI
Following severe traumatic brain injury (TBI), a complex interplay of pathomechanism, such as exitotoxicity, oxidative stress, inflammatory events, and mitochondrial dysfunction occurs. This leads to a cascade of neuronal and axonal pathologies, which ultimately lead to axonal failure, neuronal energy metabolic failure, and neuronal death, which in turn determine patient outcome. For mild and moderate TBI, the pathomechanism is similar but much less frequent and ischemic cell death is unusual, except with mass lesions. Involvement of mitochondria in acute post-traumatic neurodegeneration has been extensively studied during the last decade, and there are a number of investigations implicatin…
LACTATE, NOT GLUCOSE, UP-REGULATES MITOCHONDRIAL OXYGEN CONSUMPTION BOTHIN SHAM AND LATERAL FLUID PERCUSSED RAT BRAINS
OBJECTIVE: Failure of energy metabolism after traumatic brain injury may be a major factor limiting outcome. Although glucose is the primary metabolic substrate in the healthy brain, the well documented surge in tissue lactate after traumatic brain injury suggests that lactate may provide an energy need that cannot be met by glucose. We hypothesized, therefore, that administration of lactate or the combination of lactate and supraphysiological oxygen may improve mitochondrial oxidative respiration in the brain after rat fluid percussion injury. We measured oxygen consumption (VO2) to determine what effects glucose, lactate, oxygen, and the combination of lactate and oxygen have on mitochond…
Lactate and glucose as energy substrates and their role in traumatic brain injury and therapy
Traumatic brain injury is a leading cause of disability and mortality worldwide, but no new pharmacological treatments are clinically available. A key pathophysiological development in the understanding of traumatic brain injury is the energy crisis derived from decreased cerebral blood flow, increased energy demand and mitochondrial dysfunction. Although still controversial, new findings suggest that brain cells try to cope in these conditions by metabolizing lactate as an energy substrate ‘on-demand’ in lieu of glucose. Experimental and clinical data suggest that lactate, at least when exogenously administered, is transported from astrocytes to neurons for neuronal utilization, essential…
Validation of brain extracellular glycerol as an indicator of cellular membrane damage due to free radical activity after traumatic brain injury.
Following severe traumatic brain injury (TBI), increasing oxygen delivery to the brain has been advocated as a useful strategy to reverse mitochondrial dysfunction and improve neurological outcome. However, this might also promote overproduction of free radicals, responsible for lipid peroxidation and hence brain cell damage. Therefore, a method for monitoring this potential adverse effect in humans is desirable. Glycerol, an end product of phospholipid breakdown, easily detectable in the human brain by means of microdialysis, might represent a reliable indicator of free radical-induced cell membrane damage. Brain microdialysates were collected from 24 adult male Sprague-Dawley rats over a …