Journal of neurotrauma
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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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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.
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Journal of neurotrauma · May 2012
Comparative StudyDifferential effects of voluntary and forced exercise on stress responses after traumatic brain injury.
Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. ⋯ Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.
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Journal of neurotrauma · May 2012
Effect of blast exposure on the brain structure and cognition in Macaca fascicularis.
Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 kPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). ⋯ Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.