Journal of neurotrauma
-
Journal of neurotrauma · May 2012
Comparative StudyTBI sex dependently upregulates ET-1 to impair autoregulation, which is aggravated by phenylephrine in males but is abrogated in females.
Traumatic brain injury (TBI) contributes to morbidity in children, and boys are disproportionately represented. Endothelin-1 (ET-1) contributes to impaired autoregulation via oxygen (O₂⁻) after TBI in piglets, but its relative role in males compared with females has not been previously investigated. Increased cerebral perfusion pressure (CPP) via phenylephrine (Phe) sex dependently improves impairment of autoregulation after TBI through modulation of extracellular signal-related kinase (ERK) mitogen-activated protein kinase (MAPK) upregulation, aggravated in males, but blocked in females. ⋯ These data indicate that TBI upregulates ET-1 more in males than in females. Elevation of CPP with Phe sex dependently prevents impairment of cerebral autoregulation after TBI through modulation of ET-1, O₂⁻, and ERK mediated impairment of K channel vasodilation. These observations advocate for the consideration of development of sex-based therapies for the treatment of hemodynamic sequelae of pediatric TBI.
-
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.
-
Journal of neurotrauma · May 2012
Association between traumatic brain injury and the subsequent risk of brain cancer.
This population-based study in Taiwan aimed to investigate the risk of having a diagnosis of malignant brain tumors within 3 years after a traumatic brain injury (TBI). This study used data from the Traumatic Brain Injury Registry and the National Health Insurance Research Database. The study cohort comprised 5007 patients who had visited ambulatory care centers or had been hospitalized with a diagnosis of TBI between 2001 and 2002. ⋯ After adjusting for sociodemographic characteristics, the hazard of being diagnosed with malignant brain tumors during the 3-year follow-up period was 4.67 (95% CI: 1.84-11.83) times greater for those who sustained a TBI than for patients in the comparison cohort. In addition, we found an association between TBI severity and malignant brain tumor among patients with TBI (p=0.033). Our findings suggest a positive correlation between TBI and the relatively short-term development of malignant neoplasms of the brain.
-
Journal of neurotrauma · May 2012
Prevention of traumatic brain injury-induced neuron death by intranasal delivery of nicotinamide adenine dinucleotide.
Traumatic brain injury (TBI) is one of the most devastating injuries experienced by military personnel, as well as the general population, and can result in acute and chronic complications such as cognitive impairments. Since there are currently no effective tools for the treatment of TBI, it is of great importance to determine the mechanisms of neuronal death that characterize this insult. Several studies have indicated that TBI-induced neuronal death arises in part due to excessive activation of poly(ADP-ribose) polymerase-1 (PARP-1), which results in nicotinamide adenine dinucleotide (NAD⁺) depletion and subsequent energy failure. ⋯ In addition, delayed microglial activation normally seen after TBI was reduced by NAD⁺ treatment at 7 days after insult. Neuronal superoxide production and PARP-1 accumulation after TBI were not inhibited by NAD⁺ treatment, indicating that reactive oxygen species (ROS) production and PARP-1 activation are events that occur upstream of NAD⁺ depletion. This study suggests that intranasal delivery of NAD⁺ represents a novel, inexpensive, and non-toxic intervention for preventing TBI-induced neuronal death.
-
Journal of neurotrauma · May 2012
MicroRNA let-7i is a promising serum biomarker for blast-induced traumatic brain injury.
Blast-induced traumatic brain injury (TBI) is of significant concern in soldiers returning from the current conflicts in Iraq and Afghanistan. Incidents of TBI have increased significantly in the current conflicts compared to previous wars, and a majority of these injuries are caused by improvised explosive devices. Currently, no specific technique or biomarker is available for diagnosing TBI when no obvious clinical symptoms are present. ⋯ Five microRNAs were significantly modulated in the serum samples of these animals at three time points post-injury. Further, we also found that the levels of microRNA let-7i are also elevated in cerebrospinal fluid post-blast wave exposure. The presence of microRNA in both serum and cerebrospinal fluid immediately after injury makes microRNA let-7i an ideal candidate for further studies of biomarkers in TBI.