Journal of neurotrauma
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Journal of neurotrauma · May 2012
Preventing flow-metabolism uncoupling acutely reduces axonal injury after traumatic brain injury.
We have previously presented evidence that the development of secondary traumatic axonal injury is related to the degree of local cerebral blood flow (LCBF) and flow-metabolism uncoupling. We have now tested the hypothesis that augmenting LCBF in the acute stages after brain injury prevents further axonal injury. Data were acquired from rats with or without acetazolamide (ACZ) that was administered immediately following controlled cortical impact injury to increase cortical LCBF. ⋯ Furthermore, early LCBF augmentation prevented the injury-associated increase in the number of stained axons from 3-24 h. Additional robust stereological analysis of impaired axonal transport and neurofilament compaction in the corpus callosum and cingulum underlying the injury core confirmed the amelioration of β-APP axon density, and showed a trend, but no significant effect, on RMO14-positive axons. These data underline the importance of maintaining flow-metabolism coupling immediately after injury in order to prevent further axonal injury, in at least one population of injured axons.
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Journal of neurotrauma · May 2012
Comparative StudyEffects of hypothermia on cerebral autoregulatory vascular responses in two rodent models of traumatic brain injury.
Traumatic brain injury (TBI) can trigger disturbances of cerebral pressure autoregulation that can translate into the generation of secondary insults and increased morbidity/mortality. Few therapies have been developed to attenuate the damaging consequences of disturbed autoregulatory control, although some suggest that hypothermia may exert such protection. Here we reexamine this issue of traumatically induced autoregulatory disturbances and their modulation by hypothermic intervention, examining these phenomena in two different models of TBI. ⋯ However, with LFPI, the use of 2 h of hypothermia provided partial vascular protection. These results clearly illustrate that TBI can alter the cerebral autoregulatory vascular response to sequentially induced hypotensive insult, whereas the use of post-traumatic hypothermia provides benefit. Collectively, these studies also demonstrate that different animal models of TBI can evoke different biological responses to injury.
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There has recently been a call for the adoption of comparative effectiveness research (CER) and related research approaches for studying traumatic brain injury (TBI). These methods allow researchers to compare the effectiveness of different therapies in producing patient-oriented outcomes of interest. Heretofore, the only measures by which to compare such therapies have been mortality and rate of poor outcome. ⋯ No consistent effect or age, gender, or years of education was seen. As expected, QOL decreased with functional outcome as described by the GOSE. The results of this study will provide the groundwork for future groups seeking to apply CER methods to clinical studies of TBI.
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Journal of neurotrauma · May 2012
Attenuation of microglial activation with minocycline is not associated with changes in neurogenesis after focal traumatic brain injury in adult mice.
Neurogenesis is stimulated following injury to the adult brain and could potentially contribute to tissue repair. However, evidence suggests that microglia activated in response to injury are detrimental to the survival of new neurons, thus limiting the neurogenic response. The aim of this study was to determine the effect of the anti-inflammatory drug minocycline on neurogenesis and functional recovery after a closed head injury model of focal traumatic brain injury (TBI). ⋯ We also show for the first time in the closed head injury model, that early stages of neurogenesis were stimulated in the hippocampus and subventricular zone; however, no increase in new mature neurons occurred. Contrary to our hypothesis, despite the attenuation of activated microglia, minocycline did not support neurogenesis in the hippocampus, lateral ventricles, or pericontusional cortex, with none of the neurogenic stages being affected by treatment. These data provide evidence that a general suppression of microglial activation is insufficient to enhance neuronal production, suggesting that further work is required to elucidate the relationship between microglia and neurogenesis after TBI.
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Journal of neurotrauma · May 2012
Continuous monitoring of the Monro-Kellie doctrine: is it possible?
The Monro-Kellie doctrine describes the principle of homeostatic intracerebral volume regulation, which stipulates that the total volume of the parenchyma, cerebrospinal fluid, and blood remains constant. Hypothetically, a slow shift (e.g., brain edema development) in the irregular vasomotion-driven exchanges of these compartmental volumes may lead to increased intracranial hypertension. To evaluate this paradigm in a clinical setting and measure the processes involved in the regulation of systemic intracranial volume, we quantified cerebral blood flow velocity (CBFv) in the middle cerebral artery, arterial blood pressure (ABP), and intracranial pressure (ICP), in 238 brain-injured subjects. ⋯ The mortality rate is 5% when ICC is less than 0, and 43% when above 0.7. ICC above 0.7 was associated with terminally elevated ICP (chi-square p=0.026). We propose that the Monro-Kellie doctrine can be monitored in real time to illustrate the state of intracranial volume regulation.